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Summers B, Kim K, Lu TM, Houghton S, Trivedi A, Quintero JR, Cala-Garcia J, Pannellini T, Polverino F, Lis R, Reed HO. Lymphatic Dysfunction Models an Autoimmune Emphysema Phenotype of Chronic Obstructive Pulmonary Disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.31.564938. [PMID: 37961242 PMCID: PMC10635025 DOI: 10.1101/2023.10.31.564938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that is characterized by many clinical phenotypes. One such phenotype of COPD is defined by emphysema, pathogenic lung tertiary lymphoid organs (TLOs), and autoantibody production. We have previously shown that lymphatic dysfunction can cause lung TLO formation and lung injury in mice. We now sought to uncover whether underlying lymphatic dysfunction may be a driver of lung injury in cigarette smoke (CS)-induced COPD. We found that lung TLOs in mice with lymphatic dysfunction produce autoantibodies and are associated with a lymphatic endothelial cell subtype that expresses antigen presentation genes. Mice with underlying lymphatic dysfunction develop increased emphysema after CS exposure, with increased size and activation of TLOs. CS further increased autoantibody production in mice with lymphatic dysfunction. B-cell blockade prevented TLO formation and decreased lung injury after CS in mice with lymphatic dysfunction. Using tissue from human COPD patients, we also found evidence of a lymphatic gene signature that was specific to patients with emphysema and prominent TLOs compared to COPD patients without emphysema. Taken together, these data suggest that lymphatic dysfunction may underlie lung injury in a subset of COPD patients with an autoimmune emphysema phenotype.
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Abstract
Inflammatory bowel diseases consisting of Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to genetic susceptibility and disturbances of the microbiome, environmental exposures forming the exposome play an important role. Starting at birth, the cumulative effect of different environmental exposures combined with a predetermined genetic susceptibility is thought to cause inflammatory bowel disease. All these environmental factors are part of a Western lifestyle, suiting the high incidence rates in Europe and the United States. Whereas receiving breastfeeding, evidence of a Helicobacter pylori infection and vitamin D are important protective factors in Crohn's disease as well as ulcerative colitis, increased hygiene, experiencing a bacterial gastroenteritis in the past, urban living surroundings, air pollution, the use of antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives are likely to be the most important risk factors for both diseases. Current cigarette smoking yields a divergent effect by protecting against ulcerative colitis but increasing risk of Crohn's disease, whereas former smoking increases chances of both diseases. This review gives a clear overview of the current state of knowledge concerning the exposome. Future studies should focus on measuring this exposome yielding the possibility of combining all involved factors to one exposome risk score and our knowledge on genetic susceptibility.
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Uniken Venema WT, Voskuil MD, Dijkstra G, Weersma RK, Festen EA. The genetic background of inflammatory bowel disease: from correlation to causality. J Pathol 2016; 241:146-158. [PMID: 27785786 DOI: 10.1002/path.4817] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 09/13/2016] [Accepted: 09/27/2016] [Indexed: 12/12/2022]
Abstract
Recent studies have greatly improved our insight into the genetic background of inflammatory bowel disease (IBD). New high-throughput technologies and large-scale international collaborations have contributed to the identification of 200 independent genetic risk loci for IBD. However, in most of these loci, it is unclear which gene conveys the risk for IBD. More importantly, it is unclear which variant within or near the gene is causal to the disease. Using targeted GWAS, imputation, resequencing of risk loci, and in silico fine-mapping of densely typed loci, several causal variants have been identified in IBD risk genes, and various pathological pathways have been uncovered. Current research in the field of IBD focuses on the effect of these causal variants on gene expression and protein function. However, more elements than only the genome must be taken into account to disentangle the multifactorial pathology of IBD. The genetic risk loci identified to date only explain a small part of genetic variance in disease risk. Currently, large multi-omics studies are incorporating factors ranging from the gut microbiome to the environment. In this review, we present the progress that has been made in IBD genetic research and stress the importance of studying causality to increase our understanding of the pathogenesis of IBD. We highlight important causal genetic variants in the candidate genes NOD2, ATG16L1, IRGM, IL23R, CARD9, RNF186, and PRDM1. We describe their downstream effects on protein function and their direct effects on the gut immune system. Furthermore, we discuss the future role of genetics in unravelling disease mechanisms in IBD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Werna Tc Uniken Venema
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Michiel D Voskuil
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Eleonora Am Festen
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.,Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
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Weigmann B, Neurath MF. Th9 cells in inflammatory bowel diseases. Semin Immunopathol 2016; 39:89-95. [PMID: 27837255 DOI: 10.1007/s00281-016-0603-z] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 10/31/2016] [Indexed: 12/11/2022]
Abstract
Inflammatory bowel diseases are chronic, relapsing, immunologically mediated disorders of the gastrointestinal tract. Emerging evidence suggests a critical functional role of transcription factors and T cell-related cytokines in ulcerative colitis and Crohn's disease. Gut-residing T cells from patients with inflammatory bowel disease produce high amounts of IL-9. Experimental models of colitis highlighted that IL-9-producing T cells critically interfered with an intact barrier function of the intestinal epithelium by impacting cellular proliferation and tight junction molecules. The blockade of IL-9 was suited to significantly ameliorate the disease activity and severity in experimental models of inflammatory bowel disease thereby suggesting that targeting IL-9 might function as a novel targeted approach for therapy.
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Affiliation(s)
- Benno Weigmann
- Department of Medicine 1, Kussmaul Campus for Medical Research, Ludwig Demling Endoscopy Center of Excellence, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Markus F Neurath
- Department of Medicine 1, Kussmaul Campus for Medical Research, Ludwig Demling Endoscopy Center of Excellence, University of Erlangen-Nürnberg, Erlangen, Germany.
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Qin Z, Wan JJ, Sun Y, Wu T, Wang PY, Du P, Su DF, Yang Y, Liu X. Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3. J Mol Med (Berl) 2016; 95:221-233. [PMID: 27709266 DOI: 10.1007/s00109-016-1473-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 07/19/2016] [Accepted: 09/08/2016] [Indexed: 01/15/2023]
Abstract
Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC. KEY MESSAGE Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells. MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells. The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.
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Affiliation(s)
- Zhen Qin
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Jing-Jing Wan
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Yang Sun
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Tingyu Wu
- Department of Colorectal Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200095, People's Republic of China
| | - Peng-Yuan Wang
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Peng Du
- Department of Colorectal Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200095, People's Republic of China
| | - Ding-Feng Su
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
| | - Yili Yang
- Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, People's Republic of China.
| | - Xia Liu
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
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Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya'acov A, Goldin E. Management of Inflammatory Bowel Disease During Pregnancy. Dig Dis Sci 2016; 61:2194-2204. [PMID: 27068171 DOI: 10.1007/s10620-016-4139-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 03/21/2016] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) usually affects women during their reproductive years and many concerns arise among these young patients. Pre-pregnancy consultation with a multi-disciplinary team is very important. The team should make patients aware of the critical importance of ensuring that conception occurs during a period of disease remission. Conception during an IBD flare-up results in disease activity or even exacerbates disease in two-thirds of women. Exacerbation of the disease is associated with increased frequency of maternal and fetal complications. Drug therapy constitutes a considerable source of patient anxiety but most drugs used for treating IBD are considered safe. Therefore, continuing pharmacological therapy during pregnancy is necessary to maintain disease control. Optimization of pre-conception nutritional status and smoking cessation are also emphasized. The general guideline for most patients, except for active perianal disease patients, is to aim for vaginal delivery in the absence of obstetric contraindications. Consistent, ongoing follow-up, as detailed in this review, should allay the anxieties and fears surrounding continuing immunosuppressive drugs during pregnancy, allowing each patient to attain the optimal conditions for achieving her goal of holding a healthy baby.
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Affiliation(s)
| | - Sorina Grisaru-Granovsky
- Fetal Maternal Medicine, Obstetrics and Gynecology Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ami Ben Ya'acov
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Eran Goldin
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
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Perricone C, Versini M, Ben-Ami D, Gertel S, Watad A, Segel MJ, Ceccarelli F, Conti F, Cantarini L, Bogdanos DP, Antonelli A, Amital H, Valesini G, Shoenfeld Y. Smoke and autoimmunity: The fire behind the disease. Autoimmun Rev 2016; 15:354-74. [DOI: 10.1016/j.autrev.2016.01.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Accepted: 12/31/2015] [Indexed: 12/14/2022]
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Münch A, Tysk C, Bohr J, Madisch A, Bonderup OK, Mohrbacher R, Mueller R, Greinwald R, Ström M, Miehlke S. Smoking Status Influences Clinical Outcome in Collagenous Colitis. J Crohns Colitis 2016; 10:449-54. [PMID: 26721941 PMCID: PMC4946766 DOI: 10.1093/ecco-jcc/jjv235] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 12/14/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known. METHODS In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model. RESULTS Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome. CONCLUSION Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.
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Affiliation(s)
- Andreas Münch
- Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Curt Tysk
- Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University and Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
| | - Johan Bohr
- Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University and Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
| | - Ahmed Madisch
- Medical Department I, Siloah Hospital, Hannover, Germany
| | | | - Ralf Mohrbacher
- Research & Development, Dr Falk Pharma GmbH, Freiburg, Germany
| | - Ralph Mueller
- Research & Development, Dr Falk Pharma GmbH, Freiburg, Germany
| | | | - Magnus Ström
- Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Stephan Miehlke
- Center for Digestive Diseases, Cooperation of Internal Medicine, Hamburg, Germany
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Legaki E, Gazouli M. Influence of environmental factors in the development of inflammatory bowel diseases. World J Gastrointest Pharmacol Ther 2016; 7:112-125. [PMID: 26855817 PMCID: PMC4734944 DOI: 10.4292/wjgpt.v7.i1.112] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 10/20/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023] Open
Abstract
Idiopathic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.
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Moon CM, Jung SA, Kim SE, Song HJ, Jung Y, Ye BD, Cheon JH, Kim YS, Kim YH, Kim JS, Han DS. Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study. PLoS One 2015; 10:e0144390. [PMID: 26647084 PMCID: PMC4672933 DOI: 10.1371/journal.pone.0144390] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Accepted: 11/17/2015] [Indexed: 12/16/2022] Open
Abstract
Diagnostic delay frequently occurs in Crohn's disease (CD) patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn's Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years) (p = 0.014), concomitant upper gastrointestinal (UGI) disease (p = 0.012) and penetrating disease behavior at diagnosis (p = 0.001) were positively associated with long diagnostic delay (≥18 months). During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07-1.93; p = 0.017), internal fistulas (HR, 1.62; 95% CI, 1.12-2.33; p = 0.011), and perianal fistulas (HR, 1.38; 95% CI, 1.06-1.80; p = 0.016). However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas.
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Affiliation(s)
- Chang Mo Moon
- Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
- * E-mail:
| | - Seong-Eun Kim
- Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Hyun Joo Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Yunho Jung
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, Republic of Korea
| | - Byong Duk Ye
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - You Sun Kim
- Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Republic of Korea
| | - Young-Ho Kim
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University College of Medicine, Guri Hospital, Guri, Republic of Korea
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Johannsen A, Susin C, Gustafsson A. Smoking and inflammation: evidence for a synergistic role in chronic disease. Periodontol 2000 2015; 64:111-26. [PMID: 24320959 DOI: 10.1111/j.1600-0757.2012.00456.x] [Citation(s) in RCA: 138] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Tobacco smoking is the most important preventable risk factor for periodontitis; however, the underlying biological mechanisms responsible for the detrimental effects of smoking on periodontal health remain largely unclear. It is also well established that smoking has a negative impact on several inflammatory diseases, including rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. The aim of this paper was to review smoking-related changes in local and systemic host responses with a focus on cellular and molecular effects that could explain a hyperinflammatory response leading to periodontal destruction. Biological mechanisms that may be common to periodontal disease and other chronic inflammatory diseases were also explored, together with gene-smoking interactions. An epidemiologic perspective on the burden of smoking on periodontal health and the potential for smoking cessation is also presented. Tobacco smoking seems to induce changes ranging from decreased leukocyte chemotaxis to decreased production of immunoglobulins. Smoking also seems to cause a stronger inflammatory reaction with an increased release of potentially tissue-destructive substances (e.g. reactive oxygen species, collagenase, serine proteases and proinflammatory cytokines). These findings support a hypothesis that periodontitis is a hyperinflammatory condition rather than a hypo-inflammatory condition.
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Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am 2015; 95:1105-22, v. [PMID: 26596917 DOI: 10.1016/j.suc.2015.07.006] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) describes a group of closely related yet heterogeneous predominantly intestinal disease processes that are a result of an uncontrolled immune mediated inflammatory response. It is estimated that approximately one and a half million persons in North America have IBD. Pathogenesis of IBD involves an uncontrolled immune mediated inflammatory response in genetically predisposed individuals to a still unknown environmental trigger that interacts with the intestinal flora. There continues to be an enormous amount of information emanating from epidemiological studies providing expanded insight into the occurrence, distribution, determinants, and mechanisms of inflammatory bowel disease.
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Affiliation(s)
- Talha A Malik
- Department of Medicine-Gastroenterology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA; Department of Epidemiology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA.
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Johannsen A, Fored MC, Håkansson J, Ekbom A, Gustafsson A. Consumption of dental treatment in patients with inflammatory bowel disease, a register study. PLoS One 2015; 10:e0134001. [PMID: 26267797 PMCID: PMC4534207 DOI: 10.1371/journal.pone.0134001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 07/03/2015] [Indexed: 01/07/2023] Open
Abstract
Objective The aim of this study was to compare the consumption of dental treatment among patients with Crohn´s disease (CD) or ulcerative colitis (UC) compared to age and gender matched control groups. Design The study group comprised 2085 patients with CD and 3161 with UC from the Uppsala-Örebro region and from the Stockholm region. The patients in the cohort were diagnosed between 1960 and 1989. Patients up to 70 years of age were included in the study. The two patients groups were compared to age- and gender-matched, randomly selected control groups from the same geographic area comprising a corresponding number of participants. Results CD patients had significantly higher total number of procedures registered (p < 0.000). The difference was most pronounced for removable dentures (+65%), fillings in front teeth (+52%) and endodontic treatment (+46%) when Crohn’s patients were compared to controls (p<0.001). The corresponding figures for UC patients were also a significantly higher total number of procedures (p < 0.005), more clinical examinations (p<0.000), fillings in canines and incisors (p < 0.001) and fillings in bicuspids and molars (p < 0.000). Conclusion This study demonstrate that CD and UC individuals use more dental treatment compared to an age-gender matched control group, and more caries-related treatments. The difference was most pronounced for restorative treatment in patients with Crohn’s.
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Affiliation(s)
- Annsofi Johannsen
- Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Huddinge, Sweden
| | - Michael C. Fored
- Department of Medicine Solna, Clinical Epidemiology Unit T2, Karolinska Institutet, Stockholm, Sweden
| | - Jan Håkansson
- Department of Periodontology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Anders Ekbom
- Department of Medicine Solna, Clinical Epidemiology Unit T2, Karolinska Institutet, Stockholm, Sweden
| | - Anders Gustafsson
- Department of Medicine Solna, Clinical Epidemiology Unit T2, Karolinska Institutet, Stockholm, Sweden
- * E-mail:
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15
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Poon SS, Asher R, Jackson R, Kneebone A, Collins P, Probert C, Dibb M, Subramanian S. Body Mass Index and Smoking Affect Thioguanine Nucleotide Levels in Inflammatory Bowel Disease. J Crohns Colitis 2015; 9:640-6. [PMID: 25968584 DOI: 10.1093/ecco-jcc/jjv084] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 05/05/2015] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Optimal levels of the thiopurine metabolite, 6-thioguanine nucleotides [6-TGN] correlate with remission of inflammatory bowel disease [IBD]. Apart from variations in the thiopurine methyl transferase [TPMT] gene, little is known about other predictors of 6-TGN levels. Obesity adversely affects response to infliximab and adalimumab and clinical course in IBD, but little is known about the interaction of thiopurines and obesity. We investigated the relationship between body mass index [BMI] and 6-TGN levels and sought to examine other predictors of 6-TGN levels. METHODS This retrospective cohort study included patients with concurrent measurements of 6-TGN and BMI. The association between 6-TGN and clinical variables including BMI was estimated using a multivariable linear regression model. RESULTS Of 132 observations, 77 [58%] had Crohn's disease and 55 [42%] ulcerative colitis. BMI, smoking, and TPMT levels were associated with 6-TGN levels in multivariable analysis. Every 5kg/m(2) increase in BMI was associated with an 8% decrease in 6-TGN (0.92; 95% confidence interval [CI] 0.87-0.98; p = 0.009). Smokers had higher 6-TGN levels in comparison with non-/ex-smokers [1.43; 95% CI 1.02-2.02; p = 0.041]. Patients with intermediate TPMT had higher 6-TGN compared to those with normal levels [2.13; 95% CI 1.62-2.80; p < 0.001]. Obese patients were more likely to have sub-therapeutic 6-TGN levels and a higher methyl mercaptopurine nucleotide [MMPN/TGN] ratio despite a similar dose of thiopurines. CONCLUSIONS Active smoking and intermediate TPMT values were associated with higher 6-TGN levels but increasing BMI resulted in lower 6-TGN and higher MMPN levels. This may explain the worse outcome that has been reported previously in obese IBD subjects.
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Affiliation(s)
- Shi Sum Poon
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Rebecca Asher
- Cancer Research UK Liverpool Cancer Trials Unit, Waterhouse Building, Liverpool, UK
| | - Richard Jackson
- Cancer Research UK Liverpool Cancer Trials Unit, Waterhouse Building, Liverpool, UK
| | - Andrew Kneebone
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Paul Collins
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Chris Probert
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Martyn Dibb
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
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Increased risk of stroke among patients with Crohn's disease: a population-based matched cohort study. Int J Colorectal Dis 2015; 30:645-53. [PMID: 25608496 DOI: 10.1007/s00384-015-2132-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Crohn's disease (CD) is one type of inflammatory bowel disease (IBD) that has been speculated to share prognostic factors with the development of stroke. There is controversial information in the literature regarding the association between CD and stroke. The present cohort study estimated the risk of subsequent stroke among CD patients compared with matched comparison subjects drawn from a population-based dataset in Taiwan. METHOD This study drew data from the Taiwan National Health Insurance Database to conduct a historical cohort study. The study cohort comprised 3309 CD patients, and the comparison cohort comprised 13,236 subjects without an IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses stratifying by age group and gender. RESULTS After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with CD was found to be 1.911 (95% confidence interval (CI) = 1.65-2.22) that of comparison subjects. While we did not detect an association between stroke and CD among patients aged 30-40 years, we did detect increased risks for stroke among CD patients aged 40-50 years (HR = 2.29) and those aged over 50 years (HR = 1.88). We also found women (HR = 2.39) to be at a greater risk than men (HR = 1.50). CONCLUSION This study reports an increased HR for subsequent stroke among CD patients when compared to matched comparison patients without IBD in an Asian population.
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Zuo L, Li Y, Wang H, Wu R, Zhu W, Zhang W, Cao L, Gu L, Gong J, Li N, Li J. Cigarette smoking is associated with intestinal barrier dysfunction in the small intestine but not in the large intestine of mice. J Crohns Colitis 2014; 8:1710-22. [PMID: 25205553 DOI: 10.1016/j.crohns.2014.08.008] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Revised: 07/23/2014] [Accepted: 08/15/2014] [Indexed: 02/07/2023]
Abstract
AIMS To observe the effect of cigarette smoke (CS) on the small bowel and colon in mice and to attempt to explain the potential mechanisms that account for these effects. METHODS Male BALB/c mice age 6-8 weeks were randomly divided into a CS group and a control group (n=10 per group). CS mice were exposed to CS (five cigarettes each time, four times a day for 5 days a week using Hamburg II smoking machine and CS was diluted with air at a ratio of 1:6) for 10 weeks, and control mice were exposed to room air. After 10 weeks, mice were sacrificed for analysis (colon and small bowel). RESULTS CS exposure impaired the intestinal barrier of the small bowel, based on evidence that CS mice exhibited increased intestinal permeability, bacterial translocation, intestinal villi atrophy, damaged tight junctions and abnormal tight junction proteins. These changes were partly mediated through the activated NF-κB (p65) signalling pathway. However, no obvious changes associated with the intestinal barrier were identified in the small bowel of control mice or the colons of control or CS mice. CONCLUSIONS CS is associated with intestinal barrier dysfunction in the small intestine but not in the large intestine of mice.
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Affiliation(s)
- Lugen Zuo
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Yi Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Honggang Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Rong Wu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Weiming Zhu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
| | - Wei Zhang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lei Cao
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lili Gu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Ning Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jieshou Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS, Richter JM, Schernhammer ES, Chan AT. Sleep duration affects risk for ulcerative colitis: a prospective cohort study. Clin Gastroenterol Hepatol 2014; 12:1879-86. [PMID: 24780288 PMCID: PMC4209312 DOI: 10.1016/j.cgh.2014.04.021] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 04/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. METHODS We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. CONCLUSIONS On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
| | - Hamed Khalili
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Gauree G Konijeti
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Leslie M Higuchi
- Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
| | - Punyanganie de Silva
- Division of Gastroenterology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Charles S Fuchs
- Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Eva S Schernhammer
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Park SJ, Kim WH, Cheon JH. Clinical characteristics and treatment of inflammatory bowel disease: a comparison of Eastern and Western perspectives. World J Gastroenterol 2014; 20:11525-11537. [PMID: 25206259 PMCID: PMC4155345 DOI: 10.3748/wjg.v20.i33.11525] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Revised: 02/09/2014] [Accepted: 06/20/2014] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal inflammatory disorder with unidentified causes. Both environmental factors and genetic aspects are believed to be crucial to the pathogenesis of IBD. The incidence and prevalence of IBD have recently been increasing throughout Asia, presumably secondary to environmental changes. This increasing trend in IBD epidemiology necessitates specific health care planning and education in Asia. To this end, we must gain a precise understanding of the distinctive clinical and therapeutic characteristics of Asian patients with IBD. The phenotypes of IBD reportedly differ considerably between Asians and Caucasians. Thus, use of the same management strategies for these different populations may not be appropriate. Moreover, investigation of the Asian-specific clinical aspects of IBD offers the possibility of identifying causative factors in the pathogenesis of IBD in this geographical area. Accordingly, this review summarizes current knowledge of the phenotypic manifestations and management practices of patients with IBD, with a special focus on a comparison of Eastern and Western perspectives.
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Mortality and causes of death in patients with inflammatory bowel disease: a nationwide register study in Finland. J Crohns Colitis 2014; 8:1088-96. [PMID: 24630486 DOI: 10.1016/j.crohns.2014.02.015] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 01/29/2014] [Accepted: 02/13/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Increased mortality has been reported in Crohn's disease (CD) but mostly not in ulcerative colitis (UC). We evaluated the overall and cause-specific mortality in a nationwide cohort of patients with inflammatory bowel disease (IBD) in Finland. METHODS A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the Special Reimbursement register were diagnosed 1987-1993 and 2000-2007 and followed up to the end of 2010 by collating these figures with the national computerized Cause-of-Death Register of Statistics Finland. In each cause-of-death category, the number of deaths reported was compared to that expected in general population, and expressed as a standardized mortality ratio (SMR). RESULTS Overall mortality was increased among patients with CD (SMR 1.33, 95% confidence interval 1.21-1.46) and UC (1.10, 1.05-1.15). SMR was significantly increased for gastrointestinal causes in CD (6.53, 4.91-8.52) and UC (2.81, 2.32-3.34). Patients with UC were found also to have increased SMR from pulmonary (1.24, 1.02-1.46) and cardiovascular disease (1.14, 1.06-1.22) and cancers of the colon (1.90, 1.38-2.55), rectum (1.79, 1.14-2.69) and biliary tract (5.65, 3.54-8.54), whereas SMR from alcohol-related deaths was decreased (0.54, 0.39-0.71). Patients with CD had a significantly increased SMR for pulmonary diseases (2.01, 1.39-2.80), infections (4.27, 2.13-7.63) and cancers of the biliary tract (4.51, 1.23-11.5) and lymphoid and hematopoietic tissue (2.95, 1.85-4.45). CONCLUSIONS In this Finnish nationwide study increased overall mortality in both CD and UC was observed. The excess mortality of 14% in IBD is mainly due to deaths related to inflammation in the gut.
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Increased risk of stroke among patients with ulcerative colitis: a population-based matched cohort study. Int J Colorectal Dis 2014; 29:805-12. [PMID: 24740513 DOI: 10.1007/s00384-014-1862-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/02/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND The risk of venous thromboembolism (VTE) and the development of atherosclerosis are increased in patients with inflammatory bowel disease (IBD). Ulcerative colitis (UC) is one type of IBD; however, there is controversy in the literature regarding the association between UC and stroke. The present cohort study estimated the risk of subsequent stroke among UC patients compared with that among matched comparison subjects drawn from a population-based data set in Taiwan. METHODS This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 516 UC patients and a comparison cohort of 2,579 subjects without IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by age group and gender. RESULTS After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with UC was 2.045 (95 % confidence interval (CI) = 1.374-3.043) than that among comparison subjects. While we did not detect an association between stroke and UC among patients aged 30-40 or 40-50 years, we did detect increased risks for stroke among UC patients aged over 50 years (HR = 2.045). We also found the association to remain significant for both men (HR = 2.153) and women (HR = 2.750). CONCLUSIONS This study detected an increased HR for subsequent stroke among Taiwanese UC patients hen compared to that among matched comparison patients without IBD.
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22
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Ng SC. Epidemiology of inflammatory bowel disease: focus on Asia. Best Pract Res Clin Gastroenterol 2014; 28:363-72. [PMID: 24913377 DOI: 10.1016/j.bpg.2014.04.003] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 02/06/2014] [Accepted: 04/14/2014] [Indexed: 02/06/2023]
Abstract
The epidemiology of inflammatory bowel disease (IBD) is changing globally. Incidence and prevalence may have stabilized in high-incidence areas such as North America and Europe but they continue to rise in previously low-incidence areas such as Eastern Europe, Asia, and much of the developing world. This epidemiological shift likely relates to westernization of lifestyle, changes in diet, and improved hygiene as part of socioeconomic development in developing countries. In Asia, UC is more prevalent than CD, although the UC:CD ratio is narrowing in certain areas. Clinical manifestations of IBD in Asia resemble the Western population, but with some differences, including higher prevalence of males and ileo-colonic CD, less familial clustering, lower surgical rates and extra-intestinal manifestations. These differences may relate to time, genetics and environmental factors. Studying the epidemiology of IBD in an area of rapidly increasing incidence may lead to discovery of important etiologic factors associated with disease development.
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Affiliation(s)
- Siew C Ng
- Institute of Digestive Disease, Department of Medicine and Therapeutics, Chinese University Hong Kong, Hong Kong.
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23
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Andersen IM, Tengesdal G, Lie BA, Boberg KM, Karlsen TH, Hov JR. Effects of coffee consumption, smoking, and hormones on risk for primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2014; 12:1019-28. [PMID: 24076415 DOI: 10.1016/j.cgh.2013.09.024] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 09/06/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC. METHODS A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (control subjects). Data were analyzed from 240 patients with PSC and 245 control subjects, matched for gender and age. RESULTS A lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P = .003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P < .001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and being a coffee drinker at the age of 18 years (P = .048) were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception (51% vs 85%; P < .001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63; P < .001). CONCLUSIONS Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.
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Affiliation(s)
- Ina Marie Andersen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Guro Tengesdal
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Benedicte Alexandra Lie
- Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo
| | - Kirsten Muri Boberg
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Tom Hemming Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Johannes Roksund Hov
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo.
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Pascual V, Dieli-Crimi R, López-Palacios N, Bodas A, Medrano LM, Núñez C. Inflammatory bowel disease and celiac disease: Overlaps and differences. World J Gastroenterol 2014; 20:4846-4856. [PMID: 24803796 PMCID: PMC4009516 DOI: 10.3748/wjg.v20.i17.4846] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 01/15/2014] [Indexed: 02/06/2023] Open
Abstract
Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.
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Kohoutova D, Pecka M, Cihak M, Cyrany J, Maly J, Bures J. Prevalence of hypercoagulable disorders in inflammatory bowel disease. Scand J Gastroenterol 2014; 49:287-94. [PMID: 24328909 DOI: 10.3109/00365521.2013.870597] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE. Inflammatory bowel disease (IBD) can be associated with hypercoagulable disorders. Aim of this single-center, prospective study was an in-depth evaluation of acquired hypercoagulable states in IBD patients. METHODS. A total of 110 patients with Crohn's disease (CD) (aged 19-69; mean 40.5, median 38.5 years), 43 with ulcerative colitis (UC) (aged 17-72; mean 42, median 36 years), and 30 controls were enrolled. Full blood count, serum C-reactive protein (CRP), proteins C and S, activated protein C (APC) resistance, thrombin-antithrombin complex (TAT), F1+F2 fragments, tissue factor pathway inhibitor (TFPI) total and truncated, TFPI-factor Xa, tissue plasminogen activator (tPA) and PAI-I antigen were investigated in peripheral blood samples. RESULTS. Only 18 of 153 (11.8%) IBD patients had hemocoagulation parameters within normal range. Significant difference between IBD patients and controls was found in thrombocyte volume (p < 0.001), protein C (p = 0.025), protein S (p = 0.003), APC resistance (p < 0.001), F1+F2 fragments (p < 0.001), and tPA (p = 0.002). In CD patients who were divided into two subgroups according to serum CRP values (non-active disease: <5 mg/L; active disease ≥5 mg/L), thrombocyte count was significantly lower (p = 0.001), thrombocyte volume was significantly higher (p = 0.002), F1+F2 fragments were significantly lower (p = 0.007) and tPA was significantly higher (p = 0.038) in the subgroup with CRP <5 mg/L. In UC patients, no significant difference depending on CRP was found. CONCLUSIONS. Acquired hypercoagulable abnormalities in IBD patients are frequent. Patients with active CD, but not UC, displayed significantly different hemocoagulable parameters, when compared to non-active CD/UC subjects. In patients with active CD (with increased serum CRP concentration) and patients with active extensive UC found at endoscopy (despite low CRP values), prophylactic anticoagulation therapy should be considered.
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Affiliation(s)
- Darina Kohoutova
- 2nd Department of Internal Medicine - Gastroenterology, Charles University in Praha, Faculty of Medicine at Hradec Kralove, University Teaching Hospital , Hradec Kralove , Czech Republic
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Jussila A, Virta LJ, Pukkala E, Färkkilä MA. Malignancies in patients with inflammatory bowel disease: a nationwide register study in Finland. Scand J Gastroenterol 2013; 48:1405-13. [PMID: 24131389 DOI: 10.3109/00365521.2013.846402] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients.
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Affiliation(s)
- Airi Jussila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital , Tampere , Finland
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Zoeckler JM, Cibula DA, Morley CP, Lax MB. Predictors for return to work for those with occupational respiratory disease: clinical and structural factors. Am J Ind Med 2013; 56:1371-82. [PMID: 24114854 DOI: 10.1002/ajim.22251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/05/2013] [Indexed: 11/11/2022]
Abstract
BACKGROUND Few occupational researchers have examined "return to work" among patients with work-related respiratory diseases. In addition, prior studies have emphasized individual patient characteristics rather than a more multi-dimensional approach that includes both clinical and structural factors. METHODS A retrospective chart review identified patients with occupational respiratory diseases in the Occupational Health Clinical Center, Syracuse, NY between 1991 and 2009. We assessed predictors of work status using an exploratory, sequential mixed methods research design, multinomial (n = 188) and Cox regressions (n = 130). RESULTS The findings suggest that patients with an increased number of diagnoses, non-union members, and those who took more than a year before clinical presentation had significantly poorer work status outcomes, after adjusting for age, education level, and relevant diagnoses. CONCLUSIONS Efforts to prevent slow return to work after developing occupational respiratory disease should recognize the importance of timely access to occupational health services, disease severity, union membership, and smoking status.
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Affiliation(s)
- Jeanette M. Zoeckler
- Department of Family Medicine, Occupational Health Clinical Center; State University of New York Upstate Medical University; Syracuse New York
| | - Donald A. Cibula
- Department of Public Health and Preventive Medicine; State University of New York Upstate Medical University; Syracuse New York
| | - Christopher P. Morley
- Department of Public Health and Preventive Medicine; State University of New York Upstate Medical University; Syracuse New York
- Department of Family Medicine; State University of New York Upstate Medical University; Syracuse New York
- Department of Psychiatry and Behavioral Sciences; State University of New York Upstate Medical University; Syracuse New York
| | - Michael B. Lax
- Department of Family Medicine; State University of New York Upstate Medical University; Syracuse New York
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The role of the environment in the development of pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2013; 15:326. [PMID: 23640032 DOI: 10.1007/s11894-013-0326-4] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The incidence of inflammatory bowel disease (IBD) is rising worldwide, with a particularly sharp increase in children. Rates are highest in North America and Europe, with rapid increases noted in developing nations adopting the Westernized environment. While many genetic risk loci have been identified that predispose people to IBD, incomplete penetrance and overlapping genotypes among patients with different phenotypes inadequately explain the etiology of these chronic diseases. Therefore, environmental risk factors have been the subject of much recent research. This article reviews the role of the environment in IBD, with particular focus on early-life exposures and pediatric-onset disease. The literature surrounding environmental risk factors is reviewed, including prenatal and perinatal exposures, the hygiene hypothesis, the urban environment, infection and antibiotic use, and secondhand tobacco smoke exposure. In addition, the possible role of the environment in altering the intestinal microbiome is addressed.
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Ryan JD, Silverberg MS, Xu W, Graff LA, Targownik LE, Walker JR, Carr R, Clara I, Miller N, Rogala L, Bernstein CN. Predicting complicated Crohn's disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population-based cohort. Aliment Pharmacol Ther 2013; 38:274-83. [PMID: 23725363 DOI: 10.1111/apt.12368] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 02/20/2013] [Accepted: 05/16/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations. AIM To investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population-based cohort. METHODS One hundred and eighty-two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty-seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi-structured interviews and validated survey measures. RESULTS Sixty-five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG-positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28-7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07-4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43-12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40-5.06, P = 0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype. CONCLUSIONS ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9-10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.
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Affiliation(s)
- J D Ryan
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
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Abstract
Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] are chronic immunologically mediated diseases that are due to a dysregulated immune response to intestinal flora in a genetically susceptible host. Despite advances in genetics, the likelihood of occurrence of disease remains incompletely explained and there appears to be a strong role for the environment in mediating risk of disease. Smoking remains the most widely studied and replicated risk factor, contributing to increased risk and severity of CD while conferring protection against UC. Recent data has suggested novel risk factors. Lower plasma vitamin D is associated with an increased risk of Crohn's disease, and vitamin D supplementation may prevent relapse of disease. Several medications including oral contraceptives, post-menopausal hormone replacement, aspirin, NSAIDs, and antibiotics may increase risk of CD or UC with the mechanisms of effect remaining inadequately defined. There is continuing evidence that depression and psychosocial stress may play a role in the pathogenesis of both CD and UC, while at the same time also increasing risk for disease flares. There is also a growing understanding of the role of diet on IBD, in particular through its effect on the microbiome. Animal protein intake and n-6 fatty acids may increase risk of UC while n-3 fatty acids and dietary fiber may confer protection. The effect of diet on established disease remains poorly studied. There is need for routine measurement of a spectrum of environmental exposures in prospective studies to further our understanding.
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Feldman C, Anderson R. Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems. J Infect 2013; 67:169-84. [PMID: 23707875 DOI: 10.1016/j.jinf.2013.05.004] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 05/08/2013] [Accepted: 05/14/2013] [Indexed: 01/04/2023]
Abstract
The predisposition of cigarette smokers for development of oral and respiratory infections caused by microbial pathogens is well recognised, with those infected with the human immunodeficiency virus (HIV) at particularly high risk. Smoking cigarettes has a suppressive effect on the protective functions of airway epithelium, alveolar macrophages, dendritic cells, natural killer (NK) cells and adaptive immune mechanisms, in the setting of chronic systemic activation of neutrophils. Cigarette smoke also has a direct effect on microbial pathogens to promote the likelihood of infective disease, specifically promotion of microbial virulence and antibiotic resistance. In addition to interactions between smoking and HIV infection, a number of specific infections/clinical syndromes have been associated epidemiologically with cigarette smoking, including those of the upper and lower respiratory tract, gastrointestinal tract, central nervous and other organ systems. Smoking cessation benefits patients in many ways, including reduction of the risk of infectious disease.
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Affiliation(s)
- Charles Feldman
- Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital, South Africa.
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Jiang X, Castelao JE, Vandenberg D, Carracedo A, Redondo CM, Conti DV, Paredes Cotoré JP, Potter JD, Newcomb PA, Passarelli MN, Jenkins MA, Hopper JL, Gallinger S, Le Marchand L, Martínez ME, Ahnen DJ, Baron JA, Lindor NM, Haile RW, Gago-Dominguez M. Genetic variations in SMAD7 are associated with colorectal cancer risk in the colon cancer family registry. PLoS One 2013; 8:e60464. [PMID: 23560096 PMCID: PMC3616155 DOI: 10.1371/journal.pone.0060464] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 02/26/2013] [Indexed: 02/06/2023] Open
Abstract
Background Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. Materials and Methods 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. Results Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12–1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70–0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. Conclusions SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.
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Affiliation(s)
- Xuejuan Jiang
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, United States of America
| | - J. Esteban Castelao
- Oncology and Genetics Unit, Complejo Hospitalario Universitario de Vigo, Servicio Galego de Saude (SERGAS), Vigo, Spain
| | - David Vandenberg
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Angel Carracedo
- Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
| | - Carmen M. Redondo
- Oncology and Genetics Unit, Complejo Hospitalario Universitario de Vigo, Servicio Galego de Saude (SERGAS), Vigo, Spain
| | - David V. Conti
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Jesus P. Paredes Cotoré
- Department of Surgery, University Hospital Santiago de Compostela, Santiago de Compostela, Spain
| | - John D. Potter
- Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Polly A. Newcomb
- Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Michael N. Passarelli
- Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Mark A. Jenkins
- Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population & Global Health, The University of Melbourne, Victoria, Australia
| | - John L. Hopper
- Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population & Global Health, The University of Melbourne, Victoria, Australia
| | - Steven Gallinger
- Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Loic Le Marchand
- University of Hawaii Cancer Research Center, Honolulu, Hawaii, United States of America
| | - María E. Martínez
- University of California, San Diego Moores Cancer Center, San Diego, United States of America
| | - Dennis J. Ahnen
- Denver VA Medical Center and University of Colorado, Denver, Colorado, United States of America
| | - John A. Baron
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
| | - Noralane M. Lindor
- Department of Health Science Research, Mayo Clinic, Scottsdale, Arizona, United States of America
| | - Robert W. Haile
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Manuela Gago-Dominguez
- Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
- * E-mail:
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Gustavsson A, Magnuson A, Blomberg B, Andersson M, Halfvarson J, Tysk C. Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn's disease. Aliment Pharmacol Ther 2013. [PMID: 23205619 DOI: 10.1111/apt.12176] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Endoscopic balloon dilation is an efficacious and safe alternative to surgery as treatment of short intestinal strictures in Crohn's disease (CD). Factors predicting outcome of the procedure are not well described. AIM To evaluate whether smoking at diagnosis, treatment with azathioprine, or other clinical variables may affect clinical outcome after endoscopic dilation. The endpoint was requirement of a new intervention such as dilation or surgery with intestinal resection or strictureplasty. METHODS Retrospective study of 83 patients with CD who underwent endoscopic balloon dilation of an intestinal stricture between 1987 and 2009. RESULTS After index dilation 55/83 patients underwent a new intervention. Among current smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) among never smokers (adjusted HR: 2.50, 95% CI: 1.14-5.50, P = 0.022). After 5 years, cumulative probability of new intervention was 0.81 in smokers compared to 0.52 in never smokers; difference 0.29 (95% CI: 0.07-0.52, P = 0.01). In 16 patients, therapy with azathioprine was initiated before or shortly after the index dilation; 7/16 underwent a new intervention compared to 48/67 of those without azathioprine (HR: 0.46, 95% CI: 0.21-1.03, P = 0.06). After adjustment for other variables, the association was even weaker (HR: 0.80, 95% CI: 0.29-2.18, P = 0.668). Sex, age at diagnosis, age at first dilation, balloon size, location of stricture, and treatment period did not influence outcome. CONCLUSIONS Smoking doubles the risk of recurrent stricture formation requiring a new intervention after index dilation. Maintenance therapy with azathioprine did not influence the subsequent course and need for a new intervention.
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Affiliation(s)
- A Gustavsson
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
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Hong J, Zhang CH, Ma XP. Pathogenesis of inflammatory bowel disease and the action mechanism of moxibustion. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2012. [DOI: 10.1007/s11726-012-0598-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Jussila A, Virta LJ, Kautiainen H, Rekiaro M, Nieminen U, Färkkilä MA. Increasing incidence of inflammatory bowel diseases between 2000 and 2007: a nationwide register study in Finland. Inflamm Bowel Dis 2012; 18:555-61. [PMID: 21425214 DOI: 10.1002/ibd.21695] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Accepted: 01/28/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND The incidence of inflammatory bowel disease (IBD) is high in Western countries, but during the last decade the figures have stabilized, or only slightly increased; at the same time, an increasing incidence rate has been observed in Eastern Europe and Asia. The purpose of this study was to estimate the incidence of IBD in Finland between 2000 and 2007. METHODS New IBD cases between 2000-2007 were retrieved from the national database of special reimbursements for drugs costs. The register includes virtually all Finnish IBD patients since 1986. The incidence rates were calculated per 100,000 persons assuming a Poisson distribution. RESULTS In total, 14,214 IBD patients were identified; 10,352 had ulcerative colitis (UC) and 3,862 had Crohn's disease (CD). During the whole study period the mean annual incidence of IBD per 100,000 was 34.0: in CD 9.2 and in UC 24.8. The incidence of UC was notably higher in males (27.8) than in females (21.9). In CD the incidence rates did not differ significantly between genders. The incidence of UC increased from 22.1 in 2000-2001 to 27.4 in 2006-2007. The incidence of CD increased only slightly. CONCLUSION In Finland, the incidence of IBD is high, and UC is almost three times more common than CD. During the new millennium the incidence rate of UC has increased, while the incidence rate of CD has remained fairly stable. To the best of our knowledge, the incidence of UC in this nationwide register study is one of the highest reported to date.
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Affiliation(s)
- Airi Jussila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
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Habal FM, Huang VW. Review article: a decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient. Aliment Pharmacol Ther 2012; 35:501-15. [PMID: 22221203 DOI: 10.1111/j.1365-2036.2011.04967.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Revised: 12/07/2011] [Accepted: 12/09/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND Inflammatory bowel disease affects patients who are in their reproductive years. There are many questions regarding the management of IBD patients who are considering or who are already pregnant. These include the effect of the disease and the medications on fertility and on the pregnancy outcome. AIM To create an evidence-based decision-making algorithm to help guide physicians through the management of pregnancy in the IBD patient. METHODS A literature review using phrases that include: 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', 'pregnancy', 'fertility', 'breast feeding', 'delivery', 'surgery', 'immunomodulators', 'azathioprine', 'mercaptopurine', 'biologics', 'infliximab', 'adalimumab', 'certolizumab'. CONCLUSIONS The four decision-making nodes in the algorithm for the management of pregnancy in the IBD patient, and the key points for each one are as follows: (i) preconception counselling - pregnancy outcome is better if patients remain in remission during pregnancy, (ii) contemplating pregnancy or is already pregnant - drugs used to treat IBD appear to be safe during pregnancy, with the exception of methotrexate and thalidomide, (iii) delivery and (iv) breast feeding - drugs used to treat IBD appear to be safe during lactation, except for ciclosporin. Another key point is that biological agents may be continued up to 30 weeks gestation. The management of pregnancy in the IBD patient should be multi-disciplinary involving the patient and her partner, the family physician, the gastroenterologist and the obstetrician.
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Affiliation(s)
- F M Habal
- Department of Medicine, University Health Network, University of Toronto, ON, Canada.
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Abstract
BACKGROUND Interleukin-10 is a pleiotropic cytokine, whose main function is limitation and ultimately termination of immune responses. This is especially true for environmental interfaces such as the gastrointestinal tract. IL-10 acts as a key mediator for maintaining gut homeostasis. IL-10 knockout mice are well established as a genetic model for inflammatory bowel disease (IBD), and sequence variants in the IL-10 locus contribute to ulcerative colitis (UC). DESIGN This review covers the significance of IL-10 signalling in the intestinal immune response both in health and disease. It explains the biological role of IL-10, its deregulation in IBD and its contribution to intestinal inflammation via endoplasmic reticulum stress response. RESULTS Many IBD susceptibility genes have been discovered in the past years, linking fundamental biological systems, like innate and adaptive immunity, stress responses, autophagy and mucosal barrier to the pathogenesis of Crohn's disease (CD) and UC. IL-10 has long been known for its substantial role in regulating gut immunity, but its contribution to IBD was somewhat elusive. A recent study identified mutations in either IL-10 receptor subunits that are associated with early-onset enterocolitis, a severe phenotype of IBD. Other than genetic variants of IL-10 receptors, IL-10 and STAT3 genes are also associated with IBD, emphasizing the involvement of the IL-10 signalling cascade in the pathogenesis of CD and UC. CONCLUSIONS The discovery of inherited deregulations in the IL-10 signalling cascade is not only considered the missing link between IL-10 and intestinal homeostasis, but also demonstrates how findings made in animal models help explaining human disease.
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Affiliation(s)
- Gregor Paul
- Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Medical University of Vienna, Vienna, Austria
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Vigren L, Sjöberg K, Benoni C, Tysk C, Bohr J, Kilander A, Larsson L, Ström M, Hjortswang H. Is smoking a risk factor for collagenous colitis? Scand J Gastroenterol 2011; 46:1334-9. [PMID: 21854096 DOI: 10.3109/00365521.2011.610005] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohn's disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking in microscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. MATERIALS AND METHODS 116 patients (92 women) with median age of 62 years (interquartile range 55-73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. RESULTS Of the 116 CC patients, 37% were smokers compared with 17% of controls (p < 0.001, odds ratio (OR) 2.95). In the age group 16-44 years, 75% of CC patients were smokers compared with 15% of controls (p < 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers--at 42 years of age (median) compared with 56 years in non-smokers (p < 0.003). Although the proportion with active disease did not differ between smokers and non-smokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). CONCLUSIONS Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.
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Affiliation(s)
- Lina Vigren
- Division of Gastroenterology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
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Beamish LA, Osornio-Vargas AR, Wine E. Air pollution: An environmental factor contributing to intestinal disease. J Crohns Colitis 2011; 5:279-86. [PMID: 21683297 DOI: 10.1016/j.crohns.2011.02.017] [Citation(s) in RCA: 148] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2010] [Revised: 02/24/2011] [Accepted: 02/26/2011] [Indexed: 12/23/2022]
Abstract
The health impacts of air pollution have received much attention and have recently been subject to extensive study. Exposure to air pollutants such as particulate matter (PM) has been linked to lung and cardiovascular disease and increases in both hospital admissions and mortality. However, little attention has been given to the effects of air pollution on the intestine. The recent discovery of genes linked to susceptibility to inflammatory bowel diseases (IBD) explains only a fraction of the hereditary variance for these diseases. This, together with evidence of increases in incidence of IBD in the past few decades of enhanced industrialization, suggests that environmental factors could contribute to disease pathogenesis. Despite this, little research has examined the potential contribution of air pollution and its components to intestinal disease. Exposure of the bowel to air pollutants occurs via mucociliary clearance of PM from the lungs as well as ingestion via food and water sources. Gaseous pollutants may also induce systemic effects. Plausible mechanisms mediating the effects of air pollutants on the bowel could include direct effects on epithelial cells, systemic inflammation and immune activation, and modulation of the intestinal microbiota. Although there is limited epidemiologic evidence to confirm this, we suggest that a link between air pollution and intestinal disease exists and warrants further study. This link may explain, at least in part, how environmental factors impact on IBD epidemiology and disease pathogenesis.
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Affiliation(s)
- Leigh A Beamish
- Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, University of Alberta, Edmonton, AB, Canada
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40
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Chouraki V, Savoye G, Dauchet L, Vernier-Massouille G, Dupas JL, Merle V, Laberenne JE, Salomez JL, Lerebours E, Turck D, Cortot A, Gower-Rousseau C, Colombel JF. The changing pattern of Crohn's disease incidence in northern France: a continuing increase in the 10- to 19-year-old age bracket (1988-2007). Aliment Pharmacol Ther 2011; 33:1133-42. [PMID: 21488915 DOI: 10.1111/j.1365-2036.2011.04628.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Crohn's disease incidence rates have stabilised in industrialised countries since the 1980s. Conversely, a continuing increase in childhood-onset Crohn's disease incidence has been reported. AIM To confirm trends in inflammatory bowel disease (IBD) incidence in northern France over an extended time period (1988-2007) with a focus on childhood-onset Crohn's disease. METHODS The IBD patients recorded in the EPIMAD registry between 1988 and 2007 were included. Standardised incidence rates were calculated for Crohn's disease and ulcerative colitis in the entire population, and separately according to age. Evolution of phenotypes at diagnosis was also studied. RESULTS A total of 12 084 incident IBD cases (7428 Crohn's disease and 4656 ulcerative colitis) were recorded. Crohn's disease incidence rates increased from 5.2 cases/100 000 persons in 1988-1990 to 6.7 in 2006-2007 (+29%), stabilising after a peak at 7.1 in 1997-1999. Crohn's disease incidence rates in the 10-19-year age category increased by 71%, from 6.5 (1988-1990) to 11.1 (2006-2007). The frequency of initial ileo-colonic localisation increased from 52.9% in 1988-1990 to 68.6% in 2006-2007 (P<0.0001). Ulcerative colitis incidence rates decreased during the same period. CONCLUSIONS From 1988 to 2007, Crohn's disease incidence increased by 29% in northern France and by 71% in the 10-19-year-old age group. Consequently, studies on Crohn's disease risk factors should focus on the population under 20 years of age.
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Affiliation(s)
- V Chouraki
- Registre des Maladies Inflammatoires Chroniques de l'Intestin du Nord Ouest de la France, Epidemiology Unit, Lille University Hospital, Lille Cedex, France
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Domènech E, Carrión S, Garcia-Planella E, Mañosa M, Gordillo J, Concepción M, Guarner C, Cabré E. Smoking status and response to thiopurines in steroid-dependent inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:971-5. [PMID: 20824819 DOI: 10.1002/ibd.21456] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2010] [Accepted: 07/06/2010] [Indexed: 12/31/2022]
Abstract
BACKGROUND The influence of smoking on inflammatory bowel disease (IBD) susceptibility and on its clinical course is well known, but not its impact on drug efficacy. The aim of this study was to evaluate the response to thiopurines in patients with steroid-dependent IBD according to their smoking habits. METHODS The medical records of 163 IBD patients (103 Crohn's disease [CD], 60 ulcerative colitis [UC]) in whom thiopurines were started because of steroid-dependency were reviewed. Therapeutic response was defined by steroid-free clinical remission for at least 6 months after 12 months of starting thiopurines. Clinical data and smoking status at diagnosis, at the time thiopurines were started, and during the follow-up were registered. RESULTS A therapeutic response was obtained in 72% of CD and 61% of UC patients. Smoking habits did not influence the rate of response to thiopurines, the need for rescue therapies, or the development of penetrating/stricturing complications (CD) or proximal progression (UC). However, CD responders who continued smoking required new courses of steroids more often during follow-up. No influence of smoking was found when these outcomes were analyzed depending on gender or disease location. In the multivariate analysis, smoking status was the only predictive factor of drug tolerance. CONCLUSIONS Active smoking does not influence the response to thiopurines in steroid-dependent IBD, but may decrease the likelihood of drug tolerance.
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Affiliation(s)
- Eugeni Domènech
- Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
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López-Serrano P, Pérez-Calle JL, Pérez-Fernández MT, Fernández-Font JM, Boixeda de Miguel D, Fernández-Rodríguez CM. Environmental risk factors in inflammatory bowel diseases. Investigating the hygiene hypothesis: a Spanish case-control study. Scand J Gastroenterol 2010; 45:1464-1471. [PMID: 20704469 DOI: 10.3109/00365521.2010.510575] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Environmental factors have been implicated in the etiology of inflammatory bowel disease (IBD), but evidence for the hygiene hypothesis is unclear. We investigated the relationship between early-life infection-related exposures and risk of IBD. PATIENTS AND METHODS A hospital-based case-control study was carried out. A total of 124 cases of Crohn's disease (CD) and 146 of ulcerative colitis (UC) were compared with 235 and 278 well-matched control subjects, respectively. A multi-item questionnaire on familial history of IBD, childhood circumstances and familial socioeconomic status was carried out. RESULTS In a multivariate model, living in urban areas (odds ratio (OR) 4.58 (95% CI 2.17-10)), high educational level (OR 1.83 (95% CI 14-2.95)) and social status (OR 1.68 (95% CI 1.2-2.35)) were risk factors for CD, whereas childhood respiratory infections (OR 0.35 (95% CI 0.23-0.52)) and gastroenteritis (OR 0.55 (95% CI 0.36-0.85)) were protective factors. Living in urban areas (OR 4.6 (95% CI 2.29-9.9)), a high educational level (OR 10.3 (95% CI 2.54-42.1)) and social status (OR 2.042 (95% CI 1.31-3.17)) were also risk factors for UC, whereas respiratory infections (OR 0.42 (95% CI 0.29-0.6)) and gastroenteritis (OR: 0.6 (95% CI 0.42-0.86)) were protective factors. Appendectomy (OR 0.173 (95% CI 0.06-0.52)) and current smoking (OR 0.75 (95% CI 0.59-0.96)) were also protective for UC. CONCLUSION These results further support the hypothesis that better living conditions during childhood are associated with an increased risk for IBD, and reinforce the negative association between smoking and appendectomy and the risk of UC.
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Affiliation(s)
- Pilar López-Serrano
- Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, Spain.
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Abdrakhmanova GR, AlSharari S, Kang M, Damaj MI, Akbarali HI. {alpha}7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis. Am J Physiol Gastrointest Liver Physiol 2010; 299:G761-8. [PMID: 20595621 PMCID: PMC2950695 DOI: 10.1152/ajpgi.00175.2010] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Controlled clinical trials of nicotine transdermal patch for treatment of ulcerative colitis have been shown to improve histological and global clinical scores of colitis. Here we report that nicotine (1 microM) suppresses in vitro hyperexcitability of colonic dorsal root ganglia (DRG) (L(1)-L(2)) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation. Nicotine gradually reduced regenerative multiple-spike action potentials in colitis mice to a single action potential. Nicotine's effect on hyperexcitability of inflamed neurons was blocked in the presence of an alpha(7)-nicotinic acetylcholine receptor (nAChR) antagonist, methyllicaconitine, while choline, the alpha(7)-nAChR agonist, induced a similar effect to that of nicotine. Consistent with these findings, nicotine failed to suppress hyperexcitability in colonic DRG neurons from DSS-treated alpha(7) knockout mice. Furthermore, colonic DRG neurons from DSS-treated alpha(7) knockout mice were characterized by lower rheobase (10 +/- 5 vs. 77 +/- 13 pA, respectively) and current threshold (28 +/- 4 vs. 103 +/- 8 pA, respectively) levels than DSS-treated C57BL/J6 mice. An interesting observation of this study is that 8 of 12 colonic DRG (L(1)-L(2)) neurons from control alpha(7) knockout mice exhibited multiple-spike action potential firing while no wild-type neurons did. Overall, our findings suggest that nicotine at low 1 microM concentration suppresses in vitro hyperexcitability of inflamed colonic DRG neurons in a mouse model of acute colonic inflammation via activation of alpha(7)-nAChRs.
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Affiliation(s)
- Galya R. Abdrakhmanova
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
| | - Shakir AlSharari
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
| | - Minho Kang
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
| | - M. Imad Damaj
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
| | - Hamid I. Akbarali
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
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Ernst A, Andersen V, Østergaard M, Jacobsen BA, Dagiliene E, Pedersen IS, Drewes AM, Okkels H, Krarup HB. Genetic variants of glutathione S-transferases mu, theta, and pi display no susceptibility to inflammatory bowel disease in the Danish population. Scand J Gastroenterol 2010; 45:1068-75. [PMID: 20459366 DOI: 10.3109/00365521.2010.490594] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION A combination of genetic predisposition and interactions with environmental factors are believed to be responsible for disease phenotype and disease progression in inflammatory bowel diseases. The harmful effect of smoking and other environmental factors is believed to be highly dependent on the activity of detoxification enzymes. The aims of the study were to examine possible associations between the detoxifying glutathione S-transferases (GSTs) family mu, theta and pi gene variants and inflammatory bowel disease, and secondly to examine a potential genotype-genotype interaction between these variants. Genotype-disease phenotype associations and a possible interaction between genotype and cigarette smoking were also assessed. METHODS Three hundred and eighty-eight patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls were included in the study. Genomic DNA was used for genotyping of the GST genes using PCR or real-time PCR. RESULTS No associations were found between GST genotypes and inflammatory bowel diseases. Neither did a combination of the GST genotypes reveal any associations. No genotype-disease phenotype associations were found. Smoking was positively associated with CD and negatively associated with UC. An interaction between smoking and GSTM1*0 genotype was found for UC, where the GSTM1*0 genotype appear to strengthen the protective effect of smoking on disease susceptibility. CONCLUSION The GST genotypes do not seem to be important in susceptibility of inflammatory bowel disease in the Danish population. Nor did we find convincing evidence of associations between GST genotype and phenotypic features of inflammatory bowel diseases.
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Affiliation(s)
- Anja Ernst
- Department of Clinical Biochemistry, Section of Molecular Diagnostics, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
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Gapasin J, Van Langenberg DR, Holtmann G, Hetzel DJ, Andrews JM. Potentially avoidable surgery in inflammatory bowel disease: what proportion of patients come to resection without optimal preoperative therapy? A guidelines-based audit. Intern Med J 2010; 42:e84-8. [PMID: 20681962 DOI: 10.1111/j.1445-5994.2010.02328.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Recently, promulgated inflammatory bowel disease (IBD) guidelines seek to decrease the need for surgery by improving disease control. However, resection rates remain static. AIMS We therefore sought to determine the proportion of patients coming to surgery where preoperative management was not optimal according to guidelines. METHODS Case notes of all patients with resection surgery for IBD from January 2007 to March 2008 at a metropolitan teaching hospital were retrospectively reviewed. Judgement was made as to whether preoperative management was optimal or suboptimal depending on whether it met guidelines. RESULTS A total of 22 subjects with IBD-related resections were identified (15 males and seven females). In total, 17 had Crohn's disease (CD) (11 males) and five ulcerative colitis (UC) (four males). There were 10 smokers (nine CD and one UC). The two most common indications for surgery were inflammatory mass/abscess (n= 8) and refractory to medical therapy (n= 7). While all patients with known IBD (20/22) had seen a gastroenterologist in the past, five known IBD patients had resections undertaken without preoperative gastroenterologist input. Overall preoperative management was judged as optimal in only (9/22) 41%. Of those whose therapy did not meet guidelines (n= 13), five had azathioprine at doses <2 mg/kg, one declined therapy and nine with CD were current smokers. CONCLUSIONS Over 50% of IBD resection patients had suboptimal preoperative management, with sub-therapeutic thiopurine dosing and smoking in CD the main problems. Thus, there are significant gains to be made with better use of standard therapies, as it appears that ∼50% of resection surgery was 'potentially avoidable'.
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Affiliation(s)
- J Gapasin
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital School of Medicine, University of Adelaide, Adelaide, South Australia
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Carlens C, Hergens MP, Grunewald J, Ekbom A, Eklund A, Höglund CO, Askling J. Smoking, use of moist snuff, and risk of chronic inflammatory diseases. Am J Respir Crit Care Med 2010; 181:1217-22. [PMID: 20203245 DOI: 10.1164/rccm.200909-1338oc] [Citation(s) in RCA: 135] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
RATIONALE Cigarette smoking is emerging as a strong risk factor in the otherwise unknown etiology of chronic inflammatory diseases. Whether the same applies also to smokeless tobacco remains unknown. Nicotine is a powerful modifier of the inflammatory response. By comparing risks associated with tobacco smoking and with smokeless tobacco, the role of nicotine in the development of chronic inflammation may be evaluated. OBJECTIVES To assess and compare the risks of rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), sarcoidosis, and multiple sclerosis (MS) associated with cigarette smoking and with the use of Swedish moist snuff. METHODS We performed a cohort study of 277,777 males within a cohort of Swedish construction workers who had provided information about tobacco use in 1978-1993. Cross-linkage to the nationwide Swedish Hospital Discharge Register provided information about the occurrence of RA, UC, CD, sarcoidosis, and MS through 2004. MEASUREMENTS AND MAIN RESULTS Age-adjusted relative risks (RRs) associated with smoking and moist snuff, respectively, were estimated by Cox regression. Ever-smoking was associated with an increased risk for RA (RR, 2.1; 95% confidence interval [CI], 1.7-2.5), CD (RR, 1.5; 95% CI, 1.2-1.8), MS (RR, 1.9; 95% CI, 1.4-2.6), and UC (RR, 1.3; 95% CI, 1.1-1.5, confined to ex-smokers), and a decreased risk of sarcoidosis (RR, 0.5; 95% CI, 0.4-0.5). By contrast, ever-use of moist snuff, adjusted for smoking, was not associated with RA (RR, 1.0; 95% CI, 0.9-1.2), UC (RR, 1.1; 95% CI, 0.9-1.2), CD (RR, 0.9; 95% CI, 0.8-1.1), sarcoidosis (RR, 1.1; 95% CI, 0.8-1.5), or MS (RR, 1.0; 95% CI, 0.8-1.4). CONCLUSIONS Smokeless tobacco does not increase the risk of chronic inflammatory diseases, suggesting that inhaled nonnicotinic components of cigarette smoke are more important than nicotine itself in the etiology of these diseases.
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Affiliation(s)
- Cecilia Carlens
- Rheumatology Unit, Department of Medicine, Karolinska Universitetssjukhuset Solna, SE-171 76 Stockholm, Sweden.
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Hyphantis T, Antoniou K, Tomenson B, Tsianos E, Mavreas V, Creed F. Is the personality characteristic "impulsive sensation seeking" correlated to differences in current smoking between ulcerative colitis and Crohn's disease patients? Gen Hosp Psychiatry 2010; 32:57-65. [PMID: 20114129 DOI: 10.1016/j.genhosppsych.2009.09.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2009] [Revised: 09/08/2009] [Accepted: 09/08/2009] [Indexed: 11/30/2022]
Abstract
BACKGROUND Crohn's disease (CD) is associated with smoking, while ulcerative colitis (UC) is largely a disease of nonsmokers. We aimed to test whether the smoking-linked personality characteristic "impulsive sensation seeking" (ImpSS) is correlated to the differences in smoking in inflammatory bowel disease (IBD). METHODS In 185 IBD patients, the General Health Questionnaire and the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) were administered. The Fagerstrom Test for Nicotine Dependence was used to assess smokers' nicotine dependence. RESULTS CD patients were twice as likely to be active smokers than UC patients. CD patients presented higher ImpSS scores than UC patients, but the differences became nonsignificant after adjustment for age, gender, education and psychological distress. Multivariate analyses, however, showed that the relationship of ImpSS with current smoking was stronger in CD patients. Moderator analysis showed that the relationship of ImpSS with nicotine dependence was also greater in smokers with CD than in those with UC. No other ZKPQ subscale was correlated to disease type, current smoking or nicotine dependence. CONCLUSION ImpSS is associated with current smoking and nicotine dependence in IBD, and these associations are stronger in CD. These findings might be relevant to more effective interventions aiming at smoking cessation in CD patients.
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Affiliation(s)
- Thomas Hyphantis
- Department of Psychiatry, Medical School, University of Ioannina, Ioannina 45110, Greece.
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Abstract
Restorative proctocolectomy with IPAA is now accepted as the standard of care in most patients with a diagnosis of mucosal ulcerative or IndC requiring surgery. In patients with Crohn's colitis needing intervention, proctocolectomy with end ileostomy or subtotal colectomy with ileorectal anastomosis is still the treatment of choice. In the authors' institution they consider performing an ileal pouch for a diagnosis of Crohn's colitis requiring rectal resection provided there is no existing or previous evidence of perianal or small bowel CD. They only perform this in a well-motivated patient who understands the potential sequelae, including an increased incidence of adverse effects and reduced functional outcome, if they develop CD of the pouch. A significant amount of time must be allocated to the patient and their family when counseling them with regards to the potential surgical options and outcomes associated with each. The development of CD of the pouch is associated with a considerable pouch failure rate requiring pouch excision or indefinite ileostomy formation. It does not always herald disaster, however, and a large percentage of patients can be salvaged using a combination of medical and surgical therapy. In this patient group the maintenance of intestinal continuity and avoidance of an ostomy is often the most important factor in their perception toward quality of life. The search for a serologic or genetic marker that will predict disease outcome in this select patient group and thereby direct surgical decision making should continue. It is recommended that in the presence of Crohn's colitis the decision to perform an ileal pouch should only be made in a tertiary center under the care of gastroenterologists, histopathologists, and colorectal surgeons with experience in the management of these complex cases.
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Affiliation(s)
- Myles R Joyce
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue/A30, Cleveland, OH 44195, USA.
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Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991-2002: Incidence, diagnostic delay, and seasonal variations in onset of symptoms. J Crohns Colitis 2009; 3:115-24. [PMID: 21172254 DOI: 10.1016/j.crohns.2008.12.002] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2008] [Revised: 12/23/2008] [Accepted: 12/26/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Increasing incidence in Inflammatory Bowel Disease (IBD) has been suggested. Recent data on population based incidence rates within Europe are however scarce. Primary aim was to investigate prospectively the incidence of IBD within a well-defined geographical and administrative area of the Netherlands, the South Limburg IBD registry. Secondary aims were to study the duration of symptoms before diagnosis (lag time) and seasonal influences on the incidence of IBD. METHODS The incidence was examined using standardized registration of all newly diagnosed IBD patients, between 1-1-1991 and 1-1-2003. Medical records were reviewed to verify the diagnosis. At inclusion, diagnostic lag time was registered in months. RESULTS Age standardized incidence rates per 100,000 person-years (p-y) were: Crohn's Disease, male 4.84, female 7.58; Ulcerative Colitis, male 8.51, female 6.92; and Indeterminate Colitis, male 1.05, female 0.93. Incidence rates did not significantly changes over time in either Crohn's Disease, Ulcerative Colitis or Indeterminate Colitis. Lag time was 5 (0-360) months in Crohn's Disease, 3.0 (0-480) months in Ulcerative Colitis and 3.0 (0-180) months in Indeterminate Colitis. Lag time was not significantly different between the periods 1991-1993 and 2000-2002, and no statistical differences in the onset of symptoms per calendar month or season were found. CONCLUSIONS Our results, from the South Limburg region (the Netherlands), show no significant change in incidence rates of IBD. The incidence found is relatively high compared to other European countries. Lag time did not change during the study period, and seasonal influence of incidence rates could not be confirmed.
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Grieci T, Bütter A. The incidence of inflammatory bowel disease in the pediatric population of Southwestern Ontario. J Pediatr Surg 2009; 44:977-80. [PMID: 19433182 DOI: 10.1016/j.jpedsurg.2009.01.038] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Accepted: 01/15/2009] [Indexed: 12/14/2022]
Abstract
PURPOSE Despite a rising worldwide incidence of inflammatory bowel disease (IBD), few data exist on Canadian children. We reviewed the incidence of IBD in all children 17 years or younger in Southwestern Ontario. MATERIALS AND METHODS A chart review from 1997 to 2006 revealed 123 children with IBD. Patients were divided into 2 groups according to year of diagnosis: group 1 = 1997 to 2001 and group 2 = 2002 to 2006. Our catchment population was determined from census data. RESULTS Sex (group 1 = 52% females; group 2 = 45% females, P = .42) and age (group 1 = 12.4 +/- 3.6 years; group 2 = 12.9 +/- 3.5 years; P = .43) were similar between groups. Although the overall incidence of IBD decreased (group 1 = 14.3 cases/100,000; group 2 = 12.4 cases/100,000), the incidence of Crohn's disease nearly doubled (group 1 = 3.5 cases/100,000; group 2 = 6.01 cases/100,000) while the incidence of ulcerative colitis decreased substantially (group 1 = 10.6 cases/100,000; group 2 = 6.01 cases/100,000). The incidence of indeterminate colitis was 0.2 cases/100,000 for group 1 and 0.4 cases/100,000 for group 2. The rate of surgical intervention decreased over time, with 43% of patients requiring surgery in group 1 and 31% in group 2 (P = .17). CONCLUSION Despite a slight decrease in pediatric IBD incidence in Southwestern Ontario, the incidence of Crohn's disease has nearly doubled over the last decade. Reasons for this remain unclear, although given the relatively short time interval, environmental factors, rather than genetic changes, seem more likely.
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Affiliation(s)
- Tanya Grieci
- Division of Pediatric Surgery, Children's Hospital of Western Ontario, London, Ontario
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