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Vieujean S, Jairath V, Peyrin-Biroulet L, Dubinsky M, Iacucci M, Magro F, Danese S. Understanding the therapeutic toolkit for inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2025:10.1038/s41575-024-01035-7. [PMID: 39891014 DOI: 10.1038/s41575-024-01035-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/19/2024] [Indexed: 02/03/2025]
Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
| | - Vipul Jairath
- Division of Gastroenterology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marla Dubinsky
- Department of Paediatrics, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Fernando Magro
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy.
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Balarajah S, Martinez-Gili L, Alexander JL, Mullish BH, Perry RW, Li JV, Marchesi JR, Parkes M, Orchard TR, Hicks LC, Williams HRT. Diverse Phenotypes, Consistent Treatment: A Study of 30 997 South Asian and White Inflammatory Bowel Disease Patients Using the UK Inflammatory Bowel Disease BioResource. J Crohns Colitis 2025; 19:jjae186. [PMID: 39657589 PMCID: PMC11737890 DOI: 10.1093/ecco-jcc/jjae186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/24/2024] [Accepted: 12/05/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Studies in the UK and North America have suggested a distinct disease profile in South Asians compared to that of White populations. Disparities in the medical and surgical management of IBD in minority ethnic groups (including Black Americans and Asians) in the US have been shown, while data from Europe, including the UK, have been lacking. This study sought to evaluate South Asian (SA) and White (WH) inflammatory bowel disease (IBD) phenotypes, and to explore treatment approach variations between these cohorts in the UK using the IBD BioResource database. DESIGN Differences between WH and SA IBD patients were analysed using demographic, phenotypic and outcome data. Drug utilisation patterns and surgical outcomes were assessed in propensity score-matched (PSM) cohorts with multivariable logistic regression, Cox regression and Kaplan-Meier analysis. RESULTS 30,997 eligible patients were included. UC was the predominant disease subtype in SA (p<0.001). SA were younger at diagnosis (p<0.001), had a male preponderance (p<0.001), and were less likely to have a smoking history at diagnosis. The SA CD phenotype differed from WH, with less ileal (SA 30.3%, WH 38.4%, p=0.008) and stricturing (SA 16.9%, WH 25.6%, p<0.001) disease, but more perianal disease (SA 38.5%, WH 32.2%, p=0.009). More SA UC patients had extensive disease (SA 41.7%, WH 34.1%, p<0.001). In PSM cohorts, comparing treatments, there were no differences in 5-aminosalicylate, corticosteroid, thiopurine, anti-TNF or vedolizumab use. Survival analysis in matched cohorts showed no difference in time to surgery (CD) or colectomy (UC), and SA ethnicity was not associated with a difference in risk of surgery/colectomy. CONCLUSION Demographic and phenotypic differences exist between UK SA and WH IBD patients, highlighting distinct ethnicity-related variance, and the need for a research focus on under-represented populations. In comparing matched SA and WH patients, no disparity in medical and surgical IBD therapy in UK healthcare has been demonstrated: treatment is consistent regardless of ethnicity.
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Affiliation(s)
- Sharmili Balarajah
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Laura Martinez-Gili
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - James Leslie Alexander
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
- Department of Gastroenterology, London North West University Healthcare Trust, London, UK
| | - Benjamin Harvey Mullish
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Robert William Perry
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Jia V Li
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | | | - Miles Parkes
- Department of Medicine, University of Cambridge, Cambridge, UK
- Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Timothy Robin Orchard
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Lucy Charlotte Hicks
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Horace Richard Timothy Williams
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK
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Lakhanpal S, Aggarwal K, Kaur H, Kanwar K, Gupta V, Bhavsar J, Jain R. Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease. Intest Res 2025; 23:23-36. [PMID: 38712363 PMCID: PMC11834363 DOI: 10.5217/ir.2023.00104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 10/22/2023] [Accepted: 11/06/2023] [Indexed: 05/08/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.
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Affiliation(s)
- Samridhi Lakhanpal
- Department of Internal Medicine, Government Medical College, Amritsar, India
| | - Kanishk Aggarwal
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | - Harmanjit Kaur
- Department of Internal Medicine, Government Medical College, Patiala, India
| | - Kunal Kanwar
- Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Vasu Gupta
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | - Jill Bhavsar
- Department of Internal Medicine, Baroda Medical College, Baroda, India
| | - Rohit Jain
- Department of Internal Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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Kobayashi T, Dignass A, Roblin X, Takatori Y, Kaise T, Oortwijn A, Jamoul C, Hibi T. Filgotinib induction-study baseline characteristics of patients with ulcerative colitis who achieve sustained corticosteroid-free remission: post hoc analysis of the phase 2b/3 SELECTION study. Intest Res 2025; 23:65-75. [PMID: 39026439 PMCID: PMC11834366 DOI: 10.5217/ir.2024.00007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 04/04/2024] [Accepted: 04/15/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND/AIMS Obtaining and maintaining corticosteroid-free remission are important goals of treatment for ulcerative colitis (UC). Characteristics associated with achieving corticosteroid-free remission were assessed in filgotinib-treated patients in SELECTION, a 58-week, phase 2b/3 trial in moderately to severely active UC. METHODS This post hoc analysis used data from filgotinib-treated patients receiving corticosteroids at maintenance baseline in SELECTION. Univariate logistic regression was performed to assess induction baseline characteristics associated with 6 months of corticosteroid-free remission at week 58, defined as clinical remission without using corticosteroids for at least 6 months. RESULTS At maintenance baseline, 92 and 81 patients were receiving corticosteroids in the filgotinib 200 mg and filgotinib 100 mg groups, respectively. Age, body mass index, history of pancolitis, disease duration, fecal calprotectin levels, C-reactive protein levels, Mayo Clinic Score, concomitant corticosteroids, immunomodulators, and aminosalicylates had no statistically significant effect on the likelihood of achieving corticosteroid-free remission. Baseline characteristics associated with increased odds of corticosteroid-free remission were Mayo Clinic Endoscopic Subscore of 2 (vs. 3) in the filgotinib 200 mg and filgotinib 100 mg groups, and female (vs. male) sex, current (vs. former or never) smoking, and being biologic‑naive (vs. experienced) in the filgotinib 200 mg group. CONCLUSIONS Steroid tapering can be achieved in patients with UC receiving filgotinib 200 mg independently of baseline characteristics such as clinical activity and duration of illness. However, the likelihood of achieving corticosteroid-free remission was higher among patients who were biologic-naive, current smokers, had low endoscopic inflammatory burden and who were female.
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Affiliation(s)
- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt am Main, Germany
| | - Xavier Roblin
- IBD Unit, University Hospital of Saint-Étienne, Saint-Étienne, France
| | | | | | | | | | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
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Zhou RN, Ruan GC, Wu MX, Guo MY, Liang HZ, Bai XY, Yang H. Interaction of Th17 differentiations-related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population. J Dig Dis 2024; 25:368-379. [PMID: 39075019 DOI: 10.1111/1751-2980.13301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 05/15/2024] [Accepted: 06/20/2024] [Indexed: 07/31/2024]
Abstract
OBJECTIVES Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.
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Affiliation(s)
- Ru Ning Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei Xu Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Zheng Liang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Yin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
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Alenzi M, Schildkraut T, Hartley I, Badiani S, Ding NS, Rao V, Segal JP. The aetiology of pouchitis in patients with inflammatory bowel disease. Therap Adv Gastroenterol 2024; 17:17562848241249449. [PMID: 38812704 PMCID: PMC11135114 DOI: 10.1177/17562848241249449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 04/08/2024] [Indexed: 05/31/2024] Open
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis.
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Affiliation(s)
- Maram Alenzi
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Tamar Schildkraut
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
| | - Imogen Hartley
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Sarit Badiani
- Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Nik Sheng Ding
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Vikram Rao
- Department of General Medicine, Western Health, Footscray, VIC, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC, Australia
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Sanat ZM, Vahedi H, Malekzadeh R, Fanni Z. Epidemiologic profile of inflammatory bowel disease in Eastern Mediterranean Region (EMRO) countries: a systematic review and meta-analysis. BMC Public Health 2024; 24:1395. [PMID: 38789987 PMCID: PMC11127456 DOI: 10.1186/s12889-024-18816-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) consists of two main types: Crohn's disease (CD) and ulcerative colitis (UC). The epidemiology of IBD patients has not been comprehensively studied in EMRO countries; therefore, we conducted this meta-analysis to study the epidemiology of this disease in these countries. METHODS We searched four international databases, namely Scopus, Web of Knowledge (ISI), Medline/PubMed, and ProQuest, from inception up to the end of May 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline was used to carry out this systematic review and meta-analysis investigation. Using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist, the quality of the selected papers was assessed. RESULTS Based on the results of this study, the incidence of UC in EMRO countries was 2.65 per 100,000 (95% CI: 1.39-3.90), and the incidence of CD was 1.16 per 100,000 (95% CI: 0.73-1.59). The most commonly involved intestinal segment in CD was the terminal ileum (44.7%, 95% CI: 34.7-55.2), followed by the ileum (29.8%, 95% CI: 22.2-38.6), and colon (18.7%, 95% CI: 10.8-30.4). However, in UC patients, extensive colitis was the most common finding (32.3%, 95% CI: 26.4-38.8), followed by proctosigmoiditis (27.9%, 95% CI: 21.1-35.8), left-sided colitis (27.4%, 95% CI: 22.7-32.7), and proctitis (22.6%, 95% CI: 17.5-28.5). CONCLUSION As a result, we were able to establish the traits of IBD patients in EMRO nations. UC patients had a higher incidence than CD patients. The most common regions of involvement in CD and UC patients, respectively, were the colon and pancolitis. Compared to UC patients, CD patients had a higher history of appendectomy.
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Affiliation(s)
- Zahra Momayez Sanat
- Assistant Professor of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Fanni
- Assistant Professor of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran.
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Bhardwaj G, Riadi Y, Afzal M, Bansal P, Kaur H, Deorari M, Tonk RK, Almalki WH, Kazmi I, Alzarea SI, Kukreti N, Thangavelu L, Saleem S. The hidden threat: Environmental toxins and their effects on gut microbiota. Pathol Res Pract 2024; 255:155173. [PMID: 38364649 DOI: 10.1016/j.prp.2024.155173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/23/2024] [Accepted: 01/24/2024] [Indexed: 02/18/2024]
Abstract
The human gut microbiota (GM), which consists of a complex and diverse ecosystem of bacteria, plays a vital role in overall wellness. However, the delicate balance of this intricate system is being compromised by the widespread presence of environmental toxins. The intricate connection between contaminants in the environment and human well-being has garnered significant attention in recent times. Although many environmental pollutants and their toxicity have been identified and studied in laboratory settings and animal models, there is insufficient data concerning their relevance to human physiology. Consequently, research on the toxicity of environmental toxins in GM has gained prominence in recent years. Various factors, such as air pollution, chemicals, heavy metals, and pesticides, have a detrimental impact on the composition and functioning of the GM. This comprehensive review aims to comprehend the toxic effects of numerous environmental pollutants, including antibiotics, endocrine-disrupting chemicals, heavy metals, and pesticides, on GM by examining recent research findings. The current analysis concludes that different types of environmental toxins can lead to GM dysbiosis and have various potential adverse effects on the well-being of animals. We investigate the alterations to the GM composition induced by contaminants and their impact on overall well-being, providing a fresh perspective on research related to pollutant exposure.
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Affiliation(s)
- Gautam Bhardwaj
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar sector-3, M-B Road, New Delhi 110017, India
| | - Yassine Riadi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Muhammad Afzal
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia
| | - Pooja Bansal
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Harpreet Kaur
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh 247341, India; Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand 831001, India
| | - Mahamedha Deorari
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Rajiv Kumar Tonk
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar sector-3, M-B Road, New Delhi 110017, India.
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341 Sakaka, Aljouf, Saudi Arabia
| | - Neelima Kukreti
- School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India
| | - Lakshmi Thangavelu
- Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
| | - Shakir Saleem
- Department of Public Health. College of Health Sciences, Saudi Electronic University, Riyadh, Saudi Arabia.
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Harnik S, Abitbol CM, Haj Natour O, Yavzori M, Fudim E, Picard O, Naftali T, Broide E, Hirsch A, Selinger L, Shachar E, Yablecovitch D, Albshesh A, Coscas D, Kopylov U, Eliakim R, Ben-Horin S, Ungar B. Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study. J Crohns Colitis 2024; 18:341-348. [PMID: 37691574 DOI: 10.1093/ecco-jcc/jjad156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/20/2023] [Accepted: 09/08/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND AND AIMS Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.
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Affiliation(s)
- Sivan Harnik
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Chaya M Abitbol
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Ola Haj Natour
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Miri Yavzori
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Ella Fudim
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Orit Picard
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Timna Naftali
- Department of Gastroenterology, Meir Medical Center, Kfar Saba, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Efrat Broide
- The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ayal Hirsch
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Limor Selinger
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Eyal Shachar
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Doron Yablecovitch
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Ahmad Albshesh
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Daniel Coscas
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Bella Ungar
- Department of Gastroenterology, Sheba Medical Center Tel Hashomer, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
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10
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Gantzel RH, Vesterdal JD, Haase AM, Petersen AJ, Grønbæk H, Pedersen ML. The Prevalence of Inflammatory Bowel Disease in Greenland. Inflamm Bowel Dis 2023; 29:1879-1885. [PMID: 36702537 DOI: 10.1093/ibd/izad002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is sparsely investigated in Arctic populations. The aim of this study was to estimate the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in Greenland. METHODS Cross-sectional nationwide data on demography, anthropometry, biochemistry, and pharmacotherapy were extracted from the electronic medical records in Greenland. Diagnoses of UC and CD were based on International Classification of Diseases-Tenth Revision and International Classification of Primary Care-Second Edition coding and treatment with mesalazine. Data from Statistics Greenland were used for prevalence calculations. RESULTS In total, 254 patients in Greenland experienced IBD, with 214 cases of UC and 40 cases of CD. The overall IBD prevalence was 0.45%, distributed as 0.38% with UC and 0.07% with CD. The IBD prevalence was similar across the 5 regions of Greenland. However, a higher prevalence was observed in the region main towns with the largest populations (0.53%) compared with the small towns along the coastline (0.29%). UC patients were prescribed mesalazine treatment with a frequency of 78%. Furthermore, 10% of all IBD patients received treatment with nonspecific immunomodulators and 7% received biologics. CONCLUSIONS This study estimates the prevalence and uncovers characteristics of IBD in Greenland. Although CD may be underdiagnosed or less prevalent, the overall prevalence of IBD in Greenland parallels Scandinavian countries and North America. These results boost the knowledge on autoimmune diseases in arctic populations and may guide clinicians in their management of IBD in Greenland. Furthermore, the results may encourage research in IBD across the Arctic regions.
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Affiliation(s)
- Rasmus Hvidbjerg Gantzel
- Steno Diabetes Center Greenland, Nuuk, Greenland
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Anne-Mette Haase
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Michael Lynge Pedersen
- Steno Diabetes Center Greenland, Nuuk, Greenland
- Greenland Center for Health Research, Institute of Health and Nature, University of Greenland, Nuuk, Greenland
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11
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Świrkosz G, Szczygieł A, Logoń K, Wrześniewska M, Gomułka K. The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review. Biomedicines 2023; 11:3144. [PMID: 38137365 PMCID: PMC10740415 DOI: 10.3390/biomedicines11123144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/24/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC's pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. The purpose of the article is to show the complex interplay between ulcerative colitis and the microbiome. The literature search was conducted using the PubMed database. After a screening process of studies published before October 2023, a total of 136 articles were selected. It has been discovered that there is a fundamental correlation of a robust intestinal microbiota and the preservation of gastrointestinal health. Dysbiosis poses a grave risk to the host organism. It renders the host susceptible to infections and has been linked to the pathogenesis of chronic diseases, with particular relevance to conditions such as ulcerative colitis. Current therapeutic strategies for UC involve medications such as aminosalicylic acids, glucocorticoids, and immunosuppressive agents, although recent breakthroughs in monoclonal antibody therapies have significantly improved UC treatment. Furthermore, modulating the gut microbiome with specific compounds and probiotics holds potential for inflammation reduction, while fecal microbiota transplantation shows promise for alleviating UC symptoms. This review provides an overview of the gut microbiome's role in UC pathogenesis and treatment, emphasizing areas for further research.
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Affiliation(s)
- Gabriela Świrkosz
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Aleksandra Szczygieł
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Katarzyna Logoń
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Martyna Wrześniewska
- Student Scientific Group of Adult Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland; (G.Ś.); (K.L.)
| | - Krzysztof Gomułka
- Clinical Department of Internal Medicine, Pneumology and Allergology, Wroclaw Medical University, 50-369 Wrocław, Poland;
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12
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McCurdy JD, Weng R, Parlow S, Dawkins YM, Brar G, Oliveira L, Saloojee N, Murthy S, Kenshil S, Macdonald B, Sabri E, Moloo H, Sy R. Video Capsule Endoscopy can Identify Occult Luminal Crohn's Disease in Patients with Isolated Perianal Fistulas. J Crohns Colitis 2023; 17:1624-1630. [PMID: 37101357 DOI: 10.1093/ecco-jcc/jjad078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Indexed: 04/28/2023]
Abstract
BACKGROUND Accurate tools to distinguish Crohn's disease [CD] from cryptoglandular disease in patients with perianal fistulas without detectable luminal inflammation on ileocolonoscopy and abdominal enterography (isolated perianal fistulas [IPF]) are lacking. We assessed the ability of video capsule endoscopy [VCE] to detect luminal inflammation in patients with IPF. METHODS We studied consecutive adults [>17 years] with IPF who were evaluated by VCE after a negative ileocolonoscopy and abdominal enterography between 2013 and 2022. We defined luminal CD by VCE as diffuse erythema, three or more aphthous ulcers, or a Lewis score greater than 135. We compared rates of intestinal inflammation in this cohort with age- and sex-matched controls without perianal fistulas, who underwent VCE for other indications. We excluded persons with pre-existing inflammatory bowel disease [IBD] and exposure to non-steroidal anti-inflammatory drugs or immunosuppressive treatments. RESULTS A total of 45 patients with IPF underwent VCE without complications. Twelve patients [26%] met our definition of luminal CD. Luminal CD was more common in patients with IPF than in controls [26% vs 3%; p <0.01]. Among patients with IPF, male sex (OR [odds ratio], 9.2; 95% confidence interval [CI] [1.1-79.4]), smoking (OR, 4.5; 95% CI [0.9-21.2]), abscess (OR, 6.3; 95% CI [1.5-26.8]), rectal enhancement on magnetic resonance imaging [MRI] (OR, 9.0; 95% CI [0.8-99.3]), and positive antimicrobial serology (OR, 7.1; 95% CI, [0.7-70.0]) were more common in those with a positive VCE study. CONCLUSIONS VCE detected small intestinal inflammation suggestive of luminal CD in approximately one-quarter of patients with IPF. Larger studies are required to validate these findings.
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Affiliation(s)
- Jeffrey D McCurdy
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Robin Weng
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Simon Parlow
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Yvonne M Dawkins
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Gurmun Brar
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Liliana Oliveira
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Nav Saloojee
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Sanjay Murthy
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Sana Kenshil
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Blair Macdonald
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Medical Imaging, University of Ottawa, Ottawa, ON, Canada
| | - Elham Sabri
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Husein Moloo
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | - Richmond Sy
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
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13
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Liu R, Li D, Haritunians T, Ruan Y, Daly MJ, Huang H, McGovern DP. Profiling the inflammatory bowel diseases using genetics, serum biomarkers, and smoking information. iScience 2023; 26:108053. [PMID: 37841595 PMCID: PMC10568094 DOI: 10.1016/j.isci.2023.108053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 07/28/2023] [Accepted: 09/22/2023] [Indexed: 10/17/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are two etiologically related yet distinctive subtypes of the inflammatory bowel diseases (IBD). Differentiating CD from UC can be challenging using conventional clinical approaches in a subset of patients. We designed and evaluated a novel molecular-based prediction model aggregating genetics, serum biomarkers, and tobacco smoking information to assist the diagnosis of CD and UC in over 30,000 samples. A joint model combining genetics, serum biomarkers and smoking explains 46% (42-50%, 95% CI) of phenotypic variation. Despite modest overlaps with serum biomarkers, genetics makes unique contributions to distinguishing IBD subtypes. Smoking status only explains 1% (0-6%, 95% CI) of the phenotypic variance suggesting it may not be an effective biomarker. This study reveals that molecular-based models combining genetics, serum biomarkers, and smoking information could complement current diagnostic strategies and help classify patients based on biologic state rather than imperfect clinical parameters.
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Affiliation(s)
- Ruize Liu
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dalin Li
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Talin Haritunians
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Yunfeng Ruan
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Mark J. Daly
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Hailiang Huang
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dermot P.B. McGovern
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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14
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Hatia RI, Eluri M, Hawk ET, Shalaby A, Karatas E, Shalaby A, Abdelhakeem A, Abdel-Wahab R, Chang P, Rashid A, Jalal PK, Amos CI, Han Y, Armaghany T, Shroff RT, Li D, Javle M, Hassan MM. Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma. Cancer Epidemiol Biomarkers Prev 2023; 32:1338-1347. [PMID: 37540502 DOI: 10.1158/1055-9965.epi-23-0388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/14/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.
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Affiliation(s)
- Rikita I Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Madhulika Eluri
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ernest T Hawk
- Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Akram Shalaby
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio
| | - Elif Karatas
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Ahmed Shalaby
- Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, New Jersey
| | - Ahmed Abdelhakeem
- Department of Internal Medicine, Baptist Hospital of Southeast Texas, Beaumont, Texas
| | - Reham Abdel-Wahab
- Department of Melanoma Medicine Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
- Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ping Chang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Prasun K Jalal
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Younghun Han
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Tannaz Armaghany
- Division of Hematology & Oncology, Baylor College of Medicine, Houston, Texas
| | - Rachna T Shroff
- Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson, Arizona
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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15
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Yalcin BM, Ustaoglu M, Kirac Y. The relationship between the severity of inflammatory bowel diseases and expirium air carbon monoxide levels. Int J Colorectal Dis 2023; 38:188. [PMID: 37428260 DOI: 10.1007/s00384-023-04468-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 07/11/2023]
Abstract
INTRODUCTION We investigated the relationship between expirium air carbon monoxide (E-CO) levels and disease severity in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS After their first follow-ups, the E-CO levels of 162 patients with UC and 100 with CD were measured for four consecutive weeks. Blood samples were collected from all the patients, and their clinical severity was determined 1 month after their initial presentation. The clinical severity of CD was determined using the Harvey Bradshaw index (HBI), while the patients with UC completed the SEO clinical activity index (SEOI). The relationships between the disease severity and the means of these four E-CO readings were then compared. RESULTS The mean age of the participants was 42.28 ± 14.9 years, and 158 (60.3%) were men. In addition, 27.2% of the UC group and 44% of the CD group were smokers. The mean SEOI score was 145.7 ± 42.0 (min = 90, max = 227), and the mean HBI score was 5.75 ± 3.3 (min = 1, max = 15). Increased CO ppm (OR = -9.047 to 7.654 95% CI) and the number of cigarettes smoked per day (OR = -0.161 to 1.157 95% CI) emerged as independent risk factors for lower SEO scores in the linear regression models (p < 0.001), while the number of cigarettes smoked per day (OR = 0.271 to 1.182% 95 CI) was a risk factor for higher HBI scores (p = 0.022). CONCLUSION UC severity decreased with higher E-CO levels and the mean number of cigarettes smoked, while CD severity increased in line with the mean number of cigarettes smoked.
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Affiliation(s)
- Bektas Murat Yalcin
- Department of Family Medicine, Faculty of Medicine, Ondokuz Mayis University, Samsun, 55100, Turkey.
| | - Muge Ustaoglu
- Department of Family Medicine, Faculty of Medicine, Ondokuz Mayis University, Samsun, 55100, Turkey
| | - Yildiz Kirac
- Department of Gastroentrology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
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16
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Nelson AD, Fluxá D, Caldera F, Farraye FA, Hashash JG, Kröner PT. Thromboembolic Events in Hospitalized Patients with Inflammatory Bowel Disease. Dig Dis Sci 2023; 68:2597-2603. [PMID: 37027107 DOI: 10.1007/s10620-023-07920-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 03/10/2023] [Indexed: 04/08/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) has been associated with an increased risk of thromboembolic vascular complications. Although studies from the National Inpatient Sample (NIS) examined this association to some extent, sub-stratification for Crohn's disease (CD) and ulcerative colitis (UC) in larger studies is lacking. The aims of this study were to utilize the NIS to determine the prevalence of thromboembolic events in inpatients with IBD compared to in patients without IBD and to explore the inpatient outcomes like morbidity, mortality, and resource utilization in patients with IBD and thromboembolic events as stratified by disease subtype. METHODS This was a retrospective observational study using the NIS 2016. All patients with ICD10-CM codes for IBD were included. Patients with thromboembolic events were identified using diagnostic ICD codes and stratified into 4 categories: (1) Deep vein thrombosis (DVT), (2) Pulmonary embolism (PE), (3) Portal vein thrombosis (PVT), and (4) Mesenteric ischemia, which were then sub-stratified for CD and UC. The primary outcome was the inpatient prevalence and odds of thromboembolic events in patients with IBD compared to without IBD. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and total hospital costs and charges compared to patients with IBD and thromboembolic events. RESULTS A total of 331,950 patients with IBD were identified, of who 12,719 (3.8%) had an associated thromboembolic event. For the primary outcome, after adjusting for confounders, inpatients with IBD had higher adjusted odds of DVT (aOR 1.59, p < 0.001), PE (aOR 1.20, p < 0.001), PVT (aOR 3.18, p < 0.001) and mesenteric ischemia (aOR 2.49, p < 0.001) compared to inpatients without IBD, an observation which was confirmed for both patients with CD and UC. Inpatients with IBD and associated DVT, PE and mesenteric ischemia had higher morbidity, mortality, odds of colectomy, cost, and charges. CONCLUSIONS Inpatients with IBD have higher odds of associated thromboembolic disorders compared to patients without IBD. Furthermore, inpatients with IBD and thromboembolic events have significantly higher mortality, morbidity, colectomy rates and resource utilization. For these reasons, increased awareness and specialized strategies for the prevention and management of thromboembolic events should be considered in inpatients with IBD.
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Affiliation(s)
- Alfred D Nelson
- Division of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA.
- Advent Health Winter Park, 200 N Lakemont Av, Winter Park, 32792, USA.
| | - Daniela Fluxá
- Division of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA
| | - Freddy Caldera
- Division of Gastroenterology and Hepatology, University of Wisconsin, Madison, WI, USA
| | | | - Jana G Hashash
- Division of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA
| | - Paul T Kröner
- Division of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA
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17
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Jasper RA, Chen P, Patel R, Joseph S, Miller SD, Hutfless S. Tobacco use in Crohn's disease patients and association with disease outcomes in the United States Medicaid population, 2010-2019. JGH Open 2023; 7:291-298. [PMID: 37125247 PMCID: PMC10134760 DOI: 10.1002/jgh3.12893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/06/2023] [Accepted: 03/13/2023] [Indexed: 04/03/2023]
Abstract
Background and Aim To identify demographic factors associated with tobacco use in Crohn's disease (CD) patients in the US Medicaid population and examine how tobacco use affects disease outcomes. Methods We included Medicaid-eligible patients who had ≥1 ICD code for CD, and 1 year of eligibility before and after the initial encounter. We used ICD codes to identify tobacco use with respect to the time of diagnosis and used logistic regression to identify the association between age, sex, and race with tobacco use at any point before diagnosis and after diagnosis, and determine the association of tobacco use before and after diagnosis on disease outcomes. Results We identified 98 176 eligible patients; 74.5% had no documented use of tobacco and 25.5% used tobacco at some point; 21.1% had used tobacco before their CD diagnosis and 11.8% had used tobacco after diagnosis. The population that used tobacco had a higher proportion of women, those who were White, non-Hispanic, and those in their middle ages (21-60) than the group that did not use tobacco. Tobacco use before diagnosis resulted in higher risk of hospitalization and surgery (OR: 1.85 and 1.36, respectively). Conclusion Within the CD Medicaid population, tobacco use is more common in women than men, which differs from the general population, which is possibly a result of using diagnostic codes rather than survey data. Smoking cessation efforts should especially be directed at younger people who are at risk for CD, due to increased risk for more adverse outcomes among those who use tobacco before diagnosis.
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Affiliation(s)
- Ryan A. Jasper
- Whiting School of EngineeringJohns Hopkins UniversityBaltimoreMarylandUSA
| | - Po‐Hung Chen
- Division of Gastroenterology and Hepatology, Department of MedicineJohns Hopkins University School of MedicineBaltimoreMarylandUSA
| | - Reeha Patel
- Krieger School of Arts and SciencesJohns Hopkins UniversityBaltimoreMarylandUSA
| | - Shelly Joseph
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of PediatricsNew York University School of MedicineNew YorkNew YorkUSA
| | - Steven D. Miller
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of PediatricsJohns Hopkins University School of MedicineBaltimoreMarylandUSA
| | - Susan Hutfless
- The Gastrointestinal Epidemiology Research CenterJohns Hopkins UniversityBaltimoreMarylandUSA
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18
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Saadh MJ, Pal RS, Arias-Gonzáles JL, Orosco Gavilán JC, JC D, Mohany M, Al-Rejaie SS, Bahrami A, Kadham MJ, Amin AH, Georgia H. A Mendelian Randomization Analysis Investigates Causal Associations between Inflammatory Bowel Diseases and Variable Risk Factors. Nutrients 2023; 15:1202. [PMID: 36904201 PMCID: PMC10005338 DOI: 10.3390/nu15051202] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 02/25/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
The question of whether variable risk factors and various nutrients are causally related to inflammatory bowel diseases (IBDs) has remained unanswered so far. Thus, this study investigated whether genetically predicted risk factors and nutrients play a function in the occurrence of inflammatory bowel diseases, including ulcerative colitis (UC), non-infective colitis (NIC), and Crohn's disease (CD), using Mendelian randomization (MR) analysis. Utilizing the data of genome-wide association studies (GWASs) with 37 exposure factors, we ran Mendelian randomization analyses based on up to 458,109 participants. Univariable and multivariable MR analyses were conducted to determine causal risk factors for IBD diseases. Genetic predisposition to smoking and appendectomy as well as vegetable and fruit intake, breastfeeding, n-3 PUFAs, n-6 PUFAs, vitamin D, total cholesterol, whole-body fat mass, and physical activity were related to the risk of UC (p < 0.05). The effect of lifestyle behaviors on UC was attenuated after correcting for appendectomy. Genetically driven smoking, alcohol consumption, appendectomy, tonsillectomy, blood calcium, tea intake, autoimmune diseases, type 2 diabetes, cesarean delivery, vitamin D deficiency, and antibiotic exposure increased the risk of CD (p < 0.05), while vegetable and fruit intake, breastfeeding, physical activity, blood zinc, and n-3 PUFAs decreased the risk of CD (p < 0.05). Appendectomy, antibiotics, physical activity, blood zinc, n-3 PUFAs, and vegetable fruit intake remained significant predictors in multivariable MR (p < 0.05). Besides smoking, breastfeeding, alcoholic drinks, vegetable and fruit intake, vitamin D, appendectomy, and n-3 PUFAs were associated with NIC (p < 0.05). Smoking, alcoholic drinks, vegetable and fruit intake, vitamin D, appendectomy, and n-3 PUFAs remained significant predictors in multivariable MR (p < 0.05). Our results provide new and comprehensive evidence demonstrating that there are approving causal effects of various risk factors on IBDs. These findings also supply some suggestions for the treatment and prevention of these diseases.
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Affiliation(s)
- Mohamed J. Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan;
- Applied Science Research Center, Applied Science Private University, Amman 11152, Jordan
| | - Rashmi Saxena Pal
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144001, Punjab, India;
| | - José Luis Arias-Gonzáles
- Department of Social Sciences, Faculty of Social Studies, Pontifical University of Peru, San Miguel 15088, Peru;
| | | | - Darshan JC
- Department of Pharmacy Practice, Yenepoya Pharmacy College & Research Centre, Yenepoya Deemed to Be University, Mangalore 575018, Karnataka, India;
| | - Mohamed Mohany
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 1145, Saudi Arabia; (M.M.); (S.S.A.-R.)
| | - Salim S. Al-Rejaie
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 1145, Saudi Arabia; (M.M.); (S.S.A.-R.)
| | - Abolfazl Bahrami
- Biomedical Center for Systems Biology Science Munich, Ludwig Maximilians University, 80333 Munich, Germany
| | | | - Ali H. Amin
- Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt;
| | - Hrosti Georgia
- Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
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19
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Abdallah B, Arif M, Al-Malki M, Hourani R, Al-Maadeed T, Khodr N, Al-Kuwari G, Al-Siddiqi M, Kane T, Chivese T. The Association Between Inflammatory Bowel Disease and Exposure to Tobacco Smoking: A Case-Control Study in Qatar. Int J Gen Med 2023; 16:233-242. [PMID: 36711427 PMCID: PMC9875733 DOI: 10.2147/ijgm.s393284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/06/2023] [Indexed: 01/21/2023] Open
Abstract
Objective This research investigated the association between childhood and adulthood tobacco smoking exposure with ulcerative colitis (UC) and Crohn's disease (CD) in Qatar. Study Design and Setting In this case-control study, CD and UC cases were matched to controls of the same age and sex. The associations between UC and CD and childhood passive smoking and adulthood active smoking were assessed using conditional multivariable logistic regression. Results A total of 89 CD cases, median age of 37 years (IQR 29-47), and 362 UC cases, median age of 35 years (IQR 28-44), and equal numbers of controls were included. After multivariable logistic regression, CD was associated with higher odds of being a current smoker (OR 2.51, 95% CI 0.85-7.37, p=0.095), with weak evidence against the null hypothesis. This association was more pronounced in women, where CD was associated with both adulthood current smoking (OR 42.71, 95% CI, 1.17-1559.57, p=0.041), and childhood smoking exposure (OR 8.23, 95% CI, 1.36-49.66, p=0.021). In males, no associations were observed between CD and the smoking exposures. No associations were observed between UC and both smoking variables. Conclusion In Qatar, adulthood tobacco smoking appears to increase the odds of CD. Further, our findings suggest that both childhood and adulthood cigarette smoke exposure may possibly have a detrimental effect on the odds of CD in females but not in males, although further research is needed.
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Affiliation(s)
- Bushra Abdallah
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Mariah Arif
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Maryam Al-Malki
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Razan Hourani
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Tamader Al-Maadeed
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Nidal Khodr
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Ghaith Al-Kuwari
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Mashael Al-Siddiqi
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Tanya Kane
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Tawanda Chivese
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar,Correspondence: Tawanda Chivese, Department of Population Medicine, College of Medicine, QU Health, Qatar University, P O BOX 2713, Doha, Qatar, Tel +974 4403 7831, Email
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20
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KIRAÇ Y, YALÇIN B, USTAOĞLU M. The Relationship Between Smoking Status, Carbon Monoxide Levels, Quality of Life, and Disease Features in Inflammatory Bowel Diseases. KONURALP TIP DERGISI 2023. [DOI: 10.18521/ktd.1186958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Objective: The aim of the study was to analyze the relationship between smoking status and exhaled carbon monoxide (E-CO) levels, quality of life, and disease characteristics in patients with inflammatory bowel disease.
Methods: The demographic and disease characteristics and smoking status of 121 patients with inflammatory bowel disease who presented our hospital between 01.12.2020 and 01.03.2021 were investigated. After the first follow-up, the E-CO levels of these participants were measured every four consecutive weeks. The mean of these E-CO readings was accepted as the main E-CO value. After one month after their first application SF-36 Quality of Life Scale was applied. The relationship between these variables was investigated.
Results: The mean age of the participants was 42.06±14.9 years, and 36.3% were active smokers. While patients with Crohn’s disease (CD) exhibited a higher smoking rate, smokers with ulcerative colitis (UC) registered significantly higher mean CO ppm readings (p
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21
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Sheehan GT, Twardus SW, Cagan A, Ananthakrishnan AN. E-cigarette Use and Disease Outcomes in Inflammatory Bowel Diseases: A Case-Control Study. Dig Dis Sci 2023; 68:208-213. [PMID: 35579793 DOI: 10.1007/s10620-022-07539-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/20/2022] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Traditional cigarette use adversely impacts disease outcomes in Crohn's disease (CD). There has been a worldwide increase in the use of e-cigarettes over the past decade. The impact of use of nicotine containing e-cigarettes on disease outcomes in CD or ulcerative colitis (UC) has not been well defined. METHODS This was a retrospective case-control study of patients with CD or UC who were current users of nicotine containing e-cigarettes (cases). Each case was matched to two non-vaping controls. Our primary study outcome was a composite of new biologic initiation, switch of existing biologic therapy, or IBD-related hospitalization or surgery over 2 years. Multivariable models adjusting for relevant covariates were construction. RESULTS The study consisted of 127 patients with IBD who were current e-cigarette users compared to 251 controls. Current e-cigarette users were younger than non-users and were more likely to have had an IBD-related surgery previously. On multivariable analysis among those with CD, current e-cigarette use was not associated with higher risk of study outcome (OR 0.82, 95% CI 0.36-1.87). No difference was observed separately among those who were current or former smokers. Similarly, in those with UC, current e-cigarette use was not associated with the primary outcome (OR 1.05, 95% CI 0.33-3.39). CONCLUSION Current e-cigarette use was not associated with worse outcomes among patients with IBD. However, larger studies particularly of patients de novo initiating vaping are needed to draw robust conclusions. Patients should be discouraged from initiating vaping recognizing overall adverse health effects.
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Affiliation(s)
- Gabriel T Sheehan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 165 Cambridge Street, 9th Floor, Boston, MA, 02114, USA
| | - Shaina W Twardus
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 165 Cambridge Street, 9th Floor, Boston, MA, 02114, USA
| | - Andrew Cagan
- Research Information Science and Computing, Mass General Brigham, Somerville, MA, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 165 Cambridge Street, 9th Floor, Boston, MA, 02114, USA.
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22
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BARTOŠKA P, PALUCH Z. Treatment of Crohn's disease. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2022. [DOI: 10.23736/s0393-3660.22.04819-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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23
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Pravda J. Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide. World J Gastroenterol 2022; 28:4263-4298. [PMID: 36159014 PMCID: PMC9453768 DOI: 10.3748/wjg.v28.i31.4263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 04/19/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H2O2) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H2O2 production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H2O2 is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H2O2 mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H2O2 mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H2O2 produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H2O2, its rationale, components, and formulation is also provided.
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Affiliation(s)
- Jay Pravda
- Disease Pathogenesis, Inflammatory Disease Research Centre, Palm Beach Gardens, FL 33410, United States
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24
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Ananthakrishnan AN, Kaplan GG, Bernstein CN, Burke KE, Lochhead PJ, Sasson AN, Agrawal M, Tiong JHT, Steinberg J, Kruis W, Steinwurz F, Ahuja V, Ng SC, Rubin DT, Colombel JF, Gearry R. Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus. Lancet Gastroenterol Hepatol 2022; 7:666-678. [PMID: 35487235 DOI: 10.1016/s2468-1253(22)00021-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 06/14/2023]
Abstract
Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
| | - Gilaad G Kaplan
- Division of Gastroenterology & Hepatology, University of Calgary, Calgary, AB, Canada
| | - Charles N Bernstein
- Section of Gastroenterology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Kristin E Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Paul J Lochhead
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Alexa N Sasson
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Manasi Agrawal
- Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Aalborg University, Copenhagen, Denmark
| | - Jimmy Ho Tuan Tiong
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Joshua Steinberg
- Department of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Wolfgang Kruis
- Department of Internal Medicine, University of Cologne, Cologne, Germany
| | - Flavio Steinwurz
- Department of Gastroenterology, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Vineet Ahuja
- Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Siew C Ng
- Department of Medicine and Therapeutics, LKS Institute of Health Science and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - David T Rubin
- Department of Gastroenterology, Hepatology, and Nutrition, Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Jean-Frederic Colombel
- Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Richard Gearry
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
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25
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Krela-Kaźmierczak I, Zakerska-Banaszak O, Skrzypczak-Zielińska M, Łykowska-Szuber L, Szymczak-Tomczak A, Zawada A, Rychter AM, Ratajczak AE, Skoracka K, Skrzypczak D, Marcinkowska E, Słomski R, Dobrowolska A. Where Do We Stand in the Behavioral Pathogenesis of Inflammatory Bowel Disease? The Western Dietary Pattern and Microbiota-A Narrative Review. Nutrients 2022; 14:nu14122520. [PMID: 35745251 PMCID: PMC9230670 DOI: 10.3390/nu14122520] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the increasing knowledge with regard to IBD (inflammatory bowel disease), including ulcerative colitis (UC) and Crohn’s disease (CD), the etiology of these conditions is still not fully understood. Apart from immunological, environmental and nutritional factors, which have already been well documented, it is worthwhile to look at the possible impact of genetic factors, as well as the composition of the microbiota in patients suffering from IBD. New technologies in biochemistry allow to obtain information that can add to the current state of knowledge in IBD etiology.
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Affiliation(s)
- Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Oliwia Zakerska-Banaszak
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | | | - Liliana Łykowska-Szuber
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Alicja Ewa Ratajczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznań, Poland
| | - Dorota Skrzypczak
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
- Correspondence: (I.K.-K.); (O.Z.-B.); (D.S.)
| | - Emilia Marcinkowska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań, Poland; (M.S.-Z.); (R.S.)
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznań, Poland; (L.Ł.-S.); (A.S.-T.); (A.Z.); (A.M.R.); (A.E.R.); (K.S.); (E.M.); (A.D.)
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Edstorp J, Lampousi A, Carlsson S. Parental smoking, type 1 diabetes, and islet autoantibody positivity in the offspring: A systematic review and meta-analysis. Diabet Med 2022; 39:e14830. [PMID: 35290684 PMCID: PMC9311676 DOI: 10.1111/dme.14830] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/26/2022] [Accepted: 03/12/2022] [Indexed: 12/01/2022]
Abstract
AIMS Our aim was to synthesize current evidence on the association between parental smoking and incidence of type 1 diabetes and islet autoantibody positivity (IA) in the offspring by conducting a systematic review and meta-analysis. METHODS We searched Medline, Embase, and Cochrane Library until January 21, 2021, for human studies with parental tobacco use as exposure, type 1 diabetes or IA as outcome, and hazard, risk, or odds ratios as effect estimates. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Heterogeneity was quantified with the I2 statistic, bias with the ROBINS-I tool, and the certainty of evidence with the GRADE tool. RESULTS We identified 535 records of which 23 were eligible including 25 927 cases of type 1 diabetes. Maternal smoking during pregnancy was associated with a reduced risk of type 1 diabetes (n = 22, RR 0.78, CI 0.71-0.86, I2 =69%). Including only studies with low to moderate risk of bias indicated similar results with less heterogeneity (n = 14, RR 0.73, CI 0.68-0.79, I2 = 44%). The certainty of evidence was graded as high. There was no clear association between type 1 diabetes and neither maternal (n = 6, RR 0.95, CI 0.78-1.14, I2 = 0%) nor paternal (n = 6, RR 0.90, 0.70-1.17, I2 = 68%) smoking during childhood. Furthermore, the association between maternal smoking during pregnancy and IA was weak (n = 4, RR 0.86, CI 0.44-1.65, I2 = 71%). CONCLUSIONS Maternal smoking during pregnancy may reduce the risk of type 1 diabetes in the offspring. Further studies are needed to elucidate potential mechanisms underlying this association. REGISTRATION Prospero CRD42021236717.
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Affiliation(s)
- Jessica Edstorp
- Institute of Environmental MedicineKarolinska InstituteStockholmSweden
| | | | - Sofia Carlsson
- Institute of Environmental MedicineKarolinska InstituteStockholmSweden
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Sommer AJ, Peters A, Rommel M, Cyrys J, Grallert H, Haller D, Müller CL, Bind MAC. A randomization-based causal inference framework for uncovering environmental exposure effects on human gut microbiota. PLoS Comput Biol 2022; 18:e1010044. [PMID: 35533202 PMCID: PMC9129050 DOI: 10.1371/journal.pcbi.1010044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 05/24/2022] [Accepted: 03/21/2022] [Indexed: 12/03/2022] Open
Abstract
Statistical analysis of microbial genomic data within epidemiological cohort studies holds the promise to assess the influence of environmental exposures on both the host and the host-associated microbiome. However, the observational character of prospective cohort data and the intricate characteristics of microbiome data make it challenging to discover causal associations between environment and microbiome. Here, we introduce a causal inference framework based on the Rubin Causal Model that can help scientists to investigate such environment-host microbiome relationships, to capitalize on existing, possibly powerful, test statistics, and test plausible sharp null hypotheses. Using data from the German KORA cohort study, we illustrate our framework by designing two hypothetical randomized experiments with interventions of (i) air pollution reduction and (ii) smoking prevention. We study the effects of these interventions on the human gut microbiome by testing shifts in microbial diversity, changes in individual microbial abundances, and microbial network wiring between groups of matched subjects via randomization-based inference. In the smoking prevention scenario, we identify a small interconnected group of taxa worth further scrutiny, including Christensenellaceae and Ruminococcaceae genera, that have been previously associated with blood metabolite changes. These findings demonstrate that our framework may uncover potentially causal links between environmental exposure and the gut microbiome from observational data. We anticipate the present statistical framework to be a good starting point for further discoveries on the role of the gut microbiome in environmental health.
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Affiliation(s)
- Alice J. Sommer
- Department of Statistics, Harvard University, Cambridge, Massachusetts, United States of America
- Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-University München, Munich, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Annette Peters
- Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-University München, Munich, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
- Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - Martina Rommel
- Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Josef Cyrys
- Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Harald Grallert
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Dirk Haller
- ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany
- Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany
| | - Christian L. Müller
- Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany
- Department of Statistics, Ludwig-Maximilians-University München, Munich, Germany
- Center for Computational Mathematics, Flatiron Institute, New York City, New York, United States of America
| | - Marie-Abèle C. Bind
- Department of Statistics, Harvard University, Cambridge, Massachusetts, United States of America
- Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
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28
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Hua X, Lopes EW, Burke KE, Ananthakrishnan AN, Richter JM, Lo CH, Lochhead P, Chan AT, Khalili H. Smoking Behaviour Changes After Diagnosis of Inflammatory Bowel Disease and Risk of All-cause Mortality. J Crohns Colitis 2022; 16:1030-1038. [PMID: 35102373 PMCID: PMC9351977 DOI: 10.1093/ecco-jcc/jjac015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/30/2021] [Accepted: 01/25/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND AIMS We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality. METHODS Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed. Smoking behaviour changes were categorised as never, former [i.e., quit smoking before diagnosis], quitters [i.e., quit smoking after diagnosis], and current [i.e., continue smoking after diagnosis]. Follow-up for date and cause of death was completed through linkage to the National Death Index. Cox proportional hazard regression was used to estimate hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS Among 909 eligible CD and UC cases, 45% were never smokers, 38% were past smokers, and 16% were active smokers at the time of diagnosis. Among active smokers, 70% of patients with CD and 44% of patients with UC continued to smoke after diagnosis. In patients with CD, compared with current smokers, the multivariable-adjusted HRs [95% CI] of death were 0.19 [0.10 to 0.38] for never smokers, 0.31 [0.16 to 0.57] for former smokers, and 0.41 [0.18 to 0.93] for quitters. Similarly for UC, compared with current smokers, we observed a reduced risk of mortality for never smokers [HR = 0.23, 95% CI 0.10 to 0.51], former smokers [HR = 0.23, 95% CI 0.11 to 0.48], and quitters [HR = 0.28, 95% CI 0.11 to 0.72]. CONCLUSIONS In three cohorts of health professionals, a substantial proportion of patients with new diagnosis of CD and UC and history of smoking continued to smoke after diagnosis. Smoking cessation around the time of diagnosis was associated with a significant reduction in mortality.
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Affiliation(s)
- Xinwei Hua
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Emily W Lopes
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kristin E Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Han Lo
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Paul Lochhead
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Corresponding author: Hamed Khalili, MD, MPH, Digestive Healthcare Center, Crohn’s and Colitis Center, Massachusetts General Hospital, 165 Cambridge Street, 9th Floor, Boston, MA 02114, USA. Tel.: 617 726 7933; fax: 617 726 3080;
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29
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Barbara G, Barbaro MR, Fuschi D, Palombo M, Falangone F, Cremon C, Marasco G, Stanghellini V. Corrigendum: Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier. Front Nutr 2021; 8:790387. [PMID: 34790692 PMCID: PMC8591313 DOI: 10.3389/fnut.2021.790387] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/18/2022] Open
Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Maria Raffaella Barbaro
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Daniele Fuschi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Marta Palombo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesca Falangone
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Sapienza, Rome, Italy
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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30
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Syal G, Serrano M, Jain A, Cohen BL, Rieder F, Stone C, Abraham B, Hudesman D, Malter L, McCabe R, Holubar S, Afzali A, Cheifetz AS, Gaidos JKJ, Moss AC. Health Maintenance Consensus for Adults With Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1552-1563. [PMID: 34279600 PMCID: PMC8861367 DOI: 10.1093/ibd/izab155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. RESULTS The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.
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Affiliation(s)
- Gaurav Syal
- Cedars-Sinai Medical Center, Los Angeles, California, USA
| | | | - Animesh Jain
- University of North Carolina, Chapel Hill, North Carolina, USA
| | | | | | - Christian Stone
- Comprehensive Digestive Institute of Nevada, Las Vegas, Nevada, USA
| | | | - David Hudesman
- New York University Langone Medical Center, New York, New York, USA
| | - Lisa Malter
- NYU Grossman School of Medicine, Bellevue Hospital Center, New York, New York, USA
| | | | | | - Anita Afzali
- Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Adam S Cheifetz
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Alan C Moss
- Boston University School of Medicine, Boston, Massachusetts, USA
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31
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Piovani D, Pansieri C, Kotha SRR, Piazza AC, Comberg CL, Peyrin-Biroulet L, Danese S, Bonovas S. Ethnic Differences in the Smoking-related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2021; 15:1658-1678. [PMID: 33721889 DOI: 10.1093/ecco-jcc/jjab047] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The association between smoking and inflammatory bowel disease [IBD] relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. METHODS We systematically searched Medline/PubMed, Embase, and Scopus for studies examining tobacco smoking and the risk of developing IBD, ie, Crohn's disease [CD] or ulcerative colitis [UC]. Two authors independently extracted study data and assessed each study's risk of bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. RESULTS We synthesised 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; relative risk [RR]: 1.95, 95% confidence interval [CI]: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish. and Latin-American populations [11 studies; RR: 0.97; 95% CI: 0.83-1.13], with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC [51 studies; RR: 0.55, 95% CI: 0.48-0.64; weak evidence] irrespectively of ethnicity; however, cohort studies, large studies, and those recently published showed attenuated associations. CONCLUSIONS This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterise the genetic background of CD patients across different ethnicities to improve our understanding of the role of smoking in CD pathogenesis.
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Affiliation(s)
- Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IRCCS Humanitas Research Hospital, Milan, Italy
| | - Claudia Pansieri
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IRCCS Humanitas Research Hospital, Milan, Italy
| | - Soumya R R Kotha
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Amanda C Piazza
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IRCCS Humanitas Research Hospital, Milan, Italy
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IRCCS Humanitas Research Hospital, Milan, Italy
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32
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Barbara G, Barbaro MR, Fuschi D, Palombo M, Falangone F, Cremon C, Marasco G, Stanghellini V. Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier. Front Nutr 2021; 8:718356. [PMID: 34589512 PMCID: PMC8475765 DOI: 10.3389/fnut.2021.718356] [Citation(s) in RCA: 159] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/12/2021] [Indexed: 12/19/2022] Open
Abstract
The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Maria Raffaella Barbaro
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Daniele Fuschi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Marta Palombo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesca Falangone
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Sapienza, Rome, Italy
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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33
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Hedin CRH, Sonkoly E, Eberhardson M, Ståhle M. Inflammatory bowel disease and psoriasis: modernizing the multidisciplinary approach. J Intern Med 2021; 290:257-278. [PMID: 33942408 DOI: 10.1111/joim.13282] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 12/11/2022]
Abstract
Psoriasis and inflammatory bowel disease (IBD) are immune-mediated diseases occurring in barrier organs whose main task is to protect the organism from attack. These disorders are highly prevalent especially in northern Europe where psoriasis has a prevalence of around 3-4% and IBD around 0.3%. The prevalence of IBD in North America has been estimated at around 0.4%. The total incidence rates in northern Europe have been estimated at around 6 for Crohn's disease and 11 for ulcerative colitis per 100 000 person-years, compared with an incidence rate of around 280 per 100 000 person-years for psoriasis. Both diseases are less common in countries with a lower index of development. The rise in IBD appears to occur as populations adopt a westernized lifestyle, whereas psoriasis seems more stable and prevalence differences may derive more from variation in genetic susceptibility. The gut microbiota is clearly an important driver of IBD pathogenesis; in psoriasis, changes in gut and skin microbiota have been reported, but it is less clear whether and how these changes contribute to the pathogenesis. Large studies show that most identified genes are involved in the immune system. However, psoriasis and IBD are highly heterogeneous diseases and there is a need for more precise and deeper phenotyping to identify specific subgroups and their genetic, epigenetic and molecular signatures. Epigenetic modifications of DNA such as histone modifications, noncoding RNA effects on transcription and translation and DNA methylation are increasingly recognized as the mechanism underpinning much of the gene-environment interaction in the pathogenesis of both IBD and psoriasis. Our understanding of underlying pathogenetic mechanisms has deepened fundamentally over the past decades developing hand in hand with novel therapies targeting pathways and proinflammatory cytokines incriminated in disease. There is not only substantial overlap between psoriasis and IBD, but also there are differences with implication for therapy. In psoriasis, drugs targeting interleukin-23 and interleukin-17 have shown superior efficacy compared with anti-TNFs, whilst in IBD, drugs targeting interleukin-17 may be less beneficial. The therapeutic toolbox for psoriasis is impressive and is enlarging also for IBD. Still, there are unmet needs reflecting the heterogeneity of both diseases and there is a need for closer molecular diagnostics to allow for the development of precise therapeutics.
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Affiliation(s)
- C R H Hedin
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - E Sonkoly
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - M Eberhardson
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Department of Gastroenterology, University Hospital in Linkoping, Linkoping, Sweden
| | - M Ståhle
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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34
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Pedersen KM, Çolak Y, Vedel-Krogh S, Kobylecki CJ, Bojesen SE, Nordestgaard BG. Risk of ulcerative colitis and Crohn's disease in smokers lacks causal evidence. Eur J Epidemiol 2021; 37:735-745. [PMID: 34091767 DOI: 10.1007/s10654-021-00763-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/13/2021] [Indexed: 11/24/2022]
Abstract
Smoking has been associated with opposing risks of ulcerative colitis and Crohn's disease. Whether these observational associations reflect actual causal associations, confounding, or reverse causation is unclear. Using a Mendelian randomization approach, we tested the hypothesis that smoking protects against ulcerative colitis and is a cause of Crohn's disease. We included 118,683 white Danes aged ≥ 20 from the Copenhagen General Population Study (2003-2015) and the Copenhagen City Heart Study (1991-94 and 2001-03). During follow-up until 2018, we investigated the association of smoking and CHRNA3 rs1051730, where the T-allele is strongly associated with nicotine dependence, with risk of ulcerative colitis and Crohn's disease. We identified 1312 cases of ulcerative colitis and 671 cases of Crohn's disease. Compared to never-smokers, multivariable adjusted hazard ratios (HRs) for ulcerative colitis were 1.69(95% confidence interval [CI] 1.32-2.15) in former smokers and 2.27(1.74-2.96) in current smokers. Corresponding HRs for Crohn's disease were 1.31(0.93-1.84) and 1.93(1.34-2.78), respectively. Among ever-smokers when compared to non-carriers of the CHRNA3 rs1051730 T-allele, age and sex adjusted HRs for risk of ulcerative colitis were 1.03(95%CI 0.89-1.18) in heterozygotes and 0.91(0.72-1.16) in homozygotes. Corresponding HRs for Crohn's disease were 1.05(0.87-1.28) and 1.02(0.74-1.41), respectively. In a meta-analysis combined with UK Biobank, there was no evidence that CHRNA3 rs1051730 was associated with risk of ulcerative colitis or Crohn's disease. In conclusion, current versus never-smoking was associated with unexpected 2.3-fold risk of ulcerative colitis and expected 1.9-fold risk of Crohn's disease in prospective analyses; however, genetic evidence of lifelong increased smoking intensity did not support causal relationships.
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Affiliation(s)
- Kasper Mønsted Pedersen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Yunus Çolak
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Camilla Jannie Kobylecki
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Stig Egil Bojesen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark
| | - Børge Grønne Nordestgaard
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark. .,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. .,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. .,The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark.
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35
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Zhornitskiy A, Shen S, Le LB, Fung BM, Zhornitsky F, Liang T, Limketkai BN, Sauk JS, Tabibian JH. Rates of inflammatory bowel disease in Hispanics comparable to non-Hispanic Whites: results of a cohort study. Int J Colorectal Dis 2021; 36:1043-1051. [PMID: 33410997 DOI: 10.1007/s00384-020-03819-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/11/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Previous studies have suggested that inflammatory bowel disease (IBD) occurs at higher rates among non-Hispanic Whites (NHWs) compared to other ethnicities; however, Hispanics as the largest minority in the United States remain underrepresented in IBD research and we hypothesize that they have similar rates of IBD. We examined the epidemiology, demographics, clinical presentation, and treatment of IBD in a predominantly Hispanic cohort in Los Angeles (LA) County. METHODS This was a retrospective cohort study based at Olive View-UCLA Medical Center, one of the three major safety-net hospitals in LA County. Electronic medical records from 2015 to 2018 were queried, and biopsy-proven cases of IBD (n = 170) were identified. Outcomes included the incidence and prevalence of IBD, disease distribution, treatment, and IBD-related surgery. RESULTS The incidence of IBD among Hispanics was 175 (95% confidence interval [CI] 127-240) and 113 (95% CI 62-200) for NHWs per 100,000 person-years. Prevalence of IBD per 100,000 people was 418 (95% CI 341-512) for Hispanics and 557 (95% CI 431-739) for NHWs. Notably, the proportion of Hispanic IBD patients with a history of smoking was 21.5% vs 50.8% in NHWs (p = 0.011). There were no significant differences between the two groups with regard to Montreal classification, pharmacotherapy, or IBD-related surgery. CONCLUSIONS In one of the largest US studies of Hispanics with IBD, and the only one to have both clinical and histopathologic confirmation as inclusion criteria, we found the incidence and prevalence of IBD among Hispanics to be higher than previously recognized and comparable to NHWs. Additionally, Hispanic IBD patients had lower rates of smoking compared to NHWs.
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Affiliation(s)
- Alex Zhornitskiy
- Department of Internal Medicine, Santa Monica UCLA Medical Center, Santa Monica, CA, 90404, USA.
| | - Stacy Shen
- Department of Gastroenterology and Hepatology, University of Vermont Medical Center, Burlington, VT, USA
| | - Long B Le
- Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Brian M Fung
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
| | - Felicia Zhornitsky
- Department of Public Health, University of California, Berkeley, Berkeley, CA, USA
| | - Tom Liang
- Department of Pathology, LAC-USC Medical Center, Los Angeles, CA, USA
| | - Berkeley N Limketkai
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Jenny S Sauk
- Department of Pathology, LAC-USC Medical Center, Los Angeles, CA, USA
| | - James H Tabibian
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
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36
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Moroi R, Shiga H, Tarasawa K, Yano K, Shimoyama Y, Kuroha M, Kakuta Y, Fushimi K, Fujimori K, Kinouchi Y, Masamune A. The clinical practice of ulcerative colitis in elderly patients: An investigation using a nationwide database in Japan. JGH OPEN 2021; 5:842-848. [PMID: 34386590 PMCID: PMC8341191 DOI: 10.1002/jgh3.12541] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/12/2021] [Accepted: 03/25/2021] [Indexed: 12/16/2022]
Abstract
Background and Aim The number of elderly patients with ulcerative colitis (UC) is increasing worldwide. The clinical practice of associated treatment is still unclear. Therefore, we aimed to analyze clinical treatment realities and mortality in elderly and non‐elderly patients with UC. Methods We collected UC patients' data using the diagnosis procedure combination (DPC) database system and divided eligible patients into elderly (≥65 years) and non‐elderly (≤64 years) groups. We investigated and compared their therapeutic histories (medical treatments vs. surgery). Logistic regression analysis was conducted to identify clinical factors affecting surgery and in‐hospital death in each group. Results The rates of systemic steroid injection, molecular targeting drug usage, and surgery were not different between the two age groups. Meanwhile, the rate of in‐hospital death in elderly patients was higher than that in non‐elderly patients (2.7% vs. 0.19%, P < 0.0001). Multivariate analysis revealed that lower body mass index, treatment at an academic hospital, smoking history, molecular targeting drug use, and treatment with systemic steroid injection affected the rate of surgery in the elderly group. Multivariate analysis also revealed that male and older age affected the rate of in‐hospital death in the elderly group. Similar tendencies were also recognized in the non‐elderly group. Conclusions The clinical practice of treating elderly patients with UC is overall not different from treating non‐elderly patients with UC. Although the form of medical treatment and surgery rate for elderly patients with UC may not be significantly different from non‐elderly patients, the rate of in‐hospital death for elderly patients is higher.
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Affiliation(s)
- Rintaro Moroi
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Hisashi Shiga
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Kunio Tarasawa
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | - Kota Yano
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Yusuke Shimoyama
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Masatake Kuroha
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Yoichi Kakuta
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics Tokyo Medical and Dental University Graduate School of Medicine Bunkyo Japan
| | - Kenji Fujimori
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | | | - Atsushi Masamune
- Division of Gastroenterology Tohoku University Hospital Sendai Japan
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Sollai G, Melis M, Mastinu M, Paduano D, Chicco F, Magri S, Usai P, Hummel T, Barbarossa IT, Crnjar R. Olfactory Function in Patients with Inflammatory Bowel Disease (IBD) Is Associated with Their Body Mass Index and Polymorphism in the Odor Binding-Protein (OBPIIa) Gene. Nutrients 2021; 13:nu13020703. [PMID: 33671721 PMCID: PMC7926749 DOI: 10.3390/nu13020703] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/09/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023] Open
Abstract
Smell strongly contributes to food choice and intake, influencing energy balance and body weight; its reduction or loss has been related to malnutrition problems. Some patients with inflammatory bowel disease (IBD), mainly Crohn’s disease (CD) and ulcerative colitis (UC), are underweight, while others are overweight. Some studies suggest that changes in eating habits could be linked to specific disorders of the olfactory functions. We assessed the olfactory performance in 199 subjects (healthy control (HC) n = 99, IBD n = 100), based on the olfactory Threshold, Discrimination and Identification score (TDI score), measured with the “Sniffin’ Sticks” test. Subjects were genotyped for the rs2590498 polymorphism of the OBPIIa gene. IBD patients showed both a slightly, but significantly, lower olfactory function and a higher BMI compared to HC subjects. Threshold (in both population) and Discrimination (in IBD patients) olfactory score were affected by the OBPIIa genotype. BMI was influenced by both health status and OBPIIa genotype. A lower olfactory function may delay the satiety sensation and thus increase meal duration and body weight in IBD patients. However, the AA genotype of the OBPIIa seems to “protect” IBD patients from more severe olfactory dysfunction.
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Affiliation(s)
- Giorgia Sollai
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy; (M.M.); (M.M.); (I.T.B.); (R.C.)
- Correspondence: ; Tel.: +39-070-6754160
| | - Melania Melis
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy; (M.M.); (M.M.); (I.T.B.); (R.C.)
| | - Mariano Mastinu
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy; (M.M.); (M.M.); (I.T.B.); (R.C.)
| | - Danilo Paduano
- Department of Medical Sciences and Public Health, University of Cagliari, Presidio Policlinico of Monserrato, 09042 Cagliari, Italy; (D.P.); (F.C.); (S.M.); (P.U.)
| | - Fabio Chicco
- Department of Medical Sciences and Public Health, University of Cagliari, Presidio Policlinico of Monserrato, 09042 Cagliari, Italy; (D.P.); (F.C.); (S.M.); (P.U.)
| | - Salvatore Magri
- Department of Medical Sciences and Public Health, University of Cagliari, Presidio Policlinico of Monserrato, 09042 Cagliari, Italy; (D.P.); (F.C.); (S.M.); (P.U.)
| | - Paolo Usai
- Department of Medical Sciences and Public Health, University of Cagliari, Presidio Policlinico of Monserrato, 09042 Cagliari, Italy; (D.P.); (F.C.); (S.M.); (P.U.)
| | - Thomas Hummel
- Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, 01067 Dresden, Germany;
| | - Iole Tomassini Barbarossa
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy; (M.M.); (M.M.); (I.T.B.); (R.C.)
| | - Roberto Crnjar
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy; (M.M.); (M.M.); (I.T.B.); (R.C.)
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Georgiou AN, Ntritsos G, Papadimitriou N, Dimou N, Evangelou E. Cigarette Smoking, Coffee Consumption, Alcohol Intake, and Risk of Crohn's Disease and Ulcerative Colitis: A Mendelian Randomization Study. Inflamm Bowel Dis 2021; 27:162-168. [PMID: 32628751 DOI: 10.1093/ibd/izaa152] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Crohn's disease (CD) and ulcerative colitis (UC) are widely associated with smoking in epidemiological studies, whereas there are conflicting results for the association between CD and UC for both coffee and alcohol consumption. Herein, we aimed to investigate whether cigarette smoking and alcohol and coffee consumption are causally associated with either CD or UC. METHODS We utilized 540 genome-wide significant single-nucleotide polymorphisms for 3 potentially addictive substances-nicotine, alcohol, and caffeine-to assess the association of smoking, coffee, and alcohol consumption with CD and UC (12,194 CD cases, 12,366 UC cases, and 25,042 controls of European ancestry), using Mendelian randomization analysis. Mendelian randomization estimates were used to evaluate the effect of the exposure factors on CD and UC risk. Sensitivity analysis was employed to test for any directional pleiotropy. RESULTS We found evidence for a positive causal association between the age of smoking initiation and UC risk and between alcohol consumption and CD risk, which disappeared after sensitivity analysis for both associations (P > 0.05). No evidence for a causal association between cigarettes per day, smoking initiation, smoking cessation, and coffee consumption variables and UC or CD was found. CONCLUSIONS We found no clear evidence that either genetically predicted smoking, coffee consumption, or alcohol consumption are causally associated with the risk for CD or UC, although our findings indicate a potential positive association between the age of smoking and UC and between alcohol consumption and CD.
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Affiliation(s)
- Andrea N Georgiou
- Medical School, University of Cyprus, Nicosia, Cyprus
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Georgios Ntritsos
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
- Department of Informatics and Telecommunications, School of Informatics and Telecommunications, University of Ioannina, Arta, Greece
| | - Nikos Papadimitriou
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Niki Dimou
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Evangelos Evangelou
- Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
- Department of Epidemiology and Biostatistics, Imperial College London, London, UK
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Christensen B, Hanauer SB, Gibson PR, Turner JR, Hart J, Rubin DT. Segmental Histological Normalisation Occurs in Ulcerative Colitis but Does Not Improve Clinical Outcomes. J Crohns Colitis 2020; 14:1345-1353. [PMID: 32267926 PMCID: PMC7533894 DOI: 10.1093/ecco-jcc/jjaa068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Complete histological normalisation and reduction of inflammation severity in patients with ulcerative colitis are associated with improved clinical outcomes, but the clinical significance of normalisation of only segments of previously affected bowel is not known. We examined the prevalence, pattern, predictors, and clinical outcomes associated with segmental histological normalisation in in patients with ulcerative colitis. METHODS Medical records of patients with confirmed ulcerative colitis and more than one colonoscopy were sought. Segmental histological normalisation was defined as histological normalisation of a bowel segment [rectum, left-sided or right-sided colon] that had previous evidence of chronic histological injury. We assessed the variables influencing these findings and whether segmental normalisation was associated with improved clinical outcomes. RESULTS Of 646 patients, 32% had segmental and 10% complete histological normalisaton when compared with their maximal disease extent. Most [88%] had segmental normalisation in a proximal-to-distal direction. Others had distal-to-proximal or patchy normalisation. On multivariate analysis, only current smoking [p = 0.040] and age of diagnosis ≤16 years [p = 0.028] predicted segmental histological normalisation. Of 310 who were in clinical remission at initial colonoscopy, 77 [25%] experienced clinical relapse after median 1.3 [range 0.06-7.52] years. Only complete histological normalisation of the bowel was associated with improved relapse-free survival (hazard ratio [HR] 0.23; 95% confidence interval [CI] 0.08-0.68; p = 0.008]. CONCLUSIONS Segmental histological normalisation occurs in 32% of patients with ulcerative colitis and is increased in those who smoke or were diagnosed at younger age. Unlike complete histological normalisation, segmental normalisation does not signal improved clinical outcomes.
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Affiliation(s)
- Britt Christensen
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, VIC, Australia
- Department of Gastroenterology, Alfred Hospital and Monash University, Melbourne, VIC, Australia
| | - Stephen B Hanauer
- Digestive Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Hospital and Monash University, Melbourne, VIC, Australia
| | - Jerrold R Turner
- Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - John Hart
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
- Department of Pathology, University of Chicago Medicine, Chicago, IL, USA
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
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Kani HT, Ramai D, Caniglia E, Hudesman D, Axelrad J, Nicholson J, Hong S, Chang S. Systematic review with meta-analysis: a history of smoking is not associated with a higher risk of pouchitis. Aliment Pharmacol Ther 2020; 52:1117-1124. [PMID: 32780484 DOI: 10.1111/apt.15997] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 05/22/2020] [Accepted: 07/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ileal pouch-anal anastomosis is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis or indeterminate colitis. Tobacco smoking has been associated with protection from onset of ulcerative colitis. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. AIM To examine the influence of smoking on the risk of pouchitis. METHODS We identified 15 studies evaluating smoking as a risk factor for developing pouchitis in ulcerative colitis or indeterminate colitis patients with a history of ileal pouch-anal anastomosis in a systematic search performed from inception through May 4, 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios (RR) and 95% confidence intervals (CI). RESULTS A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.94, 95% CI 0.76-1.18, I2 = 73.7%). There was also no significant risk of pouchitis when comparing current smokers vs nonsmokers (RR = 0.93, 95% CI 0.70-1.24, I2 = 78.5%) and former smokers vs nonsmokers (RR = 0.96, 95% CI 0.74-1.23, I2 = 78.5%). CONCLUSIONS Smoking, past or present, is not associated with an increased risk for the development of pouchitis in patients with ulcerative colitis or indeterminate colitis.
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Affiliation(s)
- H Tarik Kani
- Division of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey.,Division of Gastroenterology, New York University Langone Health, New York, NY, USA
| | - Daryl Ramai
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Ellen Caniglia
- Department of Population Health, New York University Langone Health, New York, NY, USA
| | - David Hudesman
- Division of Gastroenterology, New York University Langone Health, New York, NY, USA
| | - Jordan Axelrad
- Division of Gastroenterology, New York University Langone Health, New York, NY, USA
| | - Joseph Nicholson
- NYU Health Sciences Library, New York University Langone Health, New York, NY, USA
| | - Simon Hong
- Division of Gastroenterology, New York University Langone Health, New York, NY, USA
| | - Shannon Chang
- Division of Gastroenterology, New York University Langone Health, New York, NY, USA
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Lautenschlager SA, Fournier N, Biedermann L, Pittet V, Schreiner P, Misselwitz B, Scharl M, Rogler G, Siebenhüner AR. The Influence of Breastfeeding, Cesarean Section, Pet Animals, and Urbanization on the Development of Inflammatory Bowel Disease: Data from the Swiss IBD Cohort Study. Inflamm Intest Dis 2020; 5:170-179. [PMID: 33313069 DOI: 10.1159/000509058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 05/07/2020] [Indexed: 01/14/2023] Open
Abstract
Introduction The pathophysiology of inflammatory bowel disease (IBD) is incompletely understood. Current concepts imply that environmental factors (EFs) trigger disease onset as well as flares in genetically susceptible individuals. Objective The objective of this study is to analyze the association between IBD and various EFs, which may influence the pathogenesis of the disease. Methods 2,294 patients from the Swiss IBD Cohort Study (SIBDCS) received a questionnaire regarding EF including mode of delivery, breastfeeding, animals in household, and place of residence. The control group comprised patients' childhood friends, who grew up in a similar environment ("friends cohort"). Results A total of 1,111 questionnaires were returned from SIBDCS patients (response rate: 48.4%). Breastfeeding for <6 months was associated with a decreased risk for ulcerative colitis/indeterminate colitis (UC/IC) (OR: 0.473, p = 0.006). IBD patients reported less pet animals in the household than the control group (p = 0.004). The presence of cats or dogs (OR: 0.688, p = 0.015) and pet rodents (OR: 0.598, p = 0.001) in the household before the age of 20 was inversely associated with the risk for UC/IC. Conclusion The present study underlines the importance of EFs in the pathogenesis of IBD. Overall, the development of UC/IC seems to be more affected from environmental influences than from Crohn's disease. Our results imply a protective effect of possessing pet animals in household and short breastfeeding regarding the onset of UC/IC.
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Affiliation(s)
- Severin A Lautenschlager
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine, Université de Lausanne, Lausanne, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Valerie Pittet
- Institute of Social and Preventive Medicine, Université de Lausanne, Lausanne, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Benjamin Misselwitz
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.,Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Alexander R Siebenhüner
- Clinic for Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Ramos PM, Anzai A, Duque-Estrada B, Farias DC, Melo DF, Mulinari-Brenner F, Pinto GM, Abraham LS, Santos LDN, Pirmez R, Miot HA. Risk factors for frontal fibrosing alopecia: A case-control study in a multiracial population. J Am Acad Dermatol 2020; 84:712-718. [PMID: 32835739 DOI: 10.1016/j.jaad.2020.08.076] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 08/11/2020] [Accepted: 08/14/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with unknown etiology and a worldwide rising incidence. OBJECTIVE The objective of this study was to evaluate the association of FFA with demographic and exposure factors in a Brazilian multiracial population. METHODS A multicenter case-control study was conducted in 11 referral centers throughout Brazil. The study was a case-control study that prospectively recruited 902 participants (451 patients with FFA and 451 sex-matched control individuals). Study participants completed a thorough questionnaire comprising variables grouped as baseline demographics, environmental exposure, diet, hormonal factors, allergies, and hair and skin care. RESULTS When adjusted by sex, age, menopause, and skin color, FFA was associated with hair straightening with formalin (odds ratio [OR], 3.18), use of ordinary (nondermatologic) facial soap (OR, 2.09) and facial moisturizer (OR, 1.99), thyroid disorders (OR, 1.69), and rosacea (OR, 2.08). Smokers (OR, 0.33) and users of antiresidue/clarifying shampoo (OR, 0.35) presented a negative association with FFA. There was no association with the use of sunscreen. LIMITATIONS Recall bias. CONCLUSIONS The association with moisturizers, ordinary facial soap, and hair straightening with formalin and the negative association with antiresidue/clarifying shampoo reinforce the possibility of an exogenous particle triggering FFA.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Rodrigo Pirmez
- Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil
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Salgado VCL, Luiz RR, Boéchat NLF, Leão IS, Schorr BDC, Parente JML, Lima DC, Silveira Júnior ES, Silva GOS, Almeida NP, Vieira A, de Bueno MLQ, Chebli JM, Bertges ÉR, Brugnara LMDC, Junqueira Neto C, Campbell SBG, Discacciati LL, Cézar JPS, Nunes T, Kaplan GG, Zaltman C. Risk factors associated with inflammatory bowel disease: A multicenter case-control study in Brazil. World J Gastroenterol 2020; 26:3611-3624. [PMID: 32742130 PMCID: PMC7366056 DOI: 10.3748/wjg.v26.i25.3611] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The etiology of inflammatory bowel disease (IBD) is unknown, but it is believed to be multifactorial. The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases. AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices. METHODS A multicenter case-control study was carried out with 548 Crohn's disease (CD) and 492 ulcerative colitis (UC) outpatients and 416 healthy controls, from six IBD centers within different Brazilian states at diverse socioeconomic development stages. A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied. Logistic regression model was created to assess the odds ratio (OR) with P value and 95% confidence intervals (CI). RESULTS Predictive variables for both diseases (CD and UC) were women [odd ratios (OR) = 1.31; OR = 1.69], low monthly family income (OR = 1.78; OR = 1.57), lower number of cohabitants (OR = 1.70; OR = 1.60), absence of vaccination (OR = 3.11; OR = 2.51), previous history of bowel infections (OR = 1.78; OR = 1.49), and family history of IBD (OR = 5.26; OR = 3.33). Associated risk factors for CD were age (18-39 years) (OR = 1.73), higher educational level (OR = 2.22), absence of infectious childhood diseases (OR = 1.99). The UC predictive variables were living in an urban area (OR = 1.62), inadequate living conditions (OR = 1.48) and former smokers (OR = 3.36). Appendectomy was a risk factor for CD (OR = 1.58) with inverse association with UC (OR = 4.79). Consumption of treated and untreated water was associated with risk of CD (OR = 1.38) and UC (OR = 1.53), respectively. CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil. Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.
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Affiliation(s)
- Valéria Cristina Loureiro Salgado
- Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
| | - Ronir Raggio Luiz
- Institute for Studies in Public Health, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
| | - Neio Lucio Fernandes Boéchat
- Multidisciplinary Research Laboratory, Clementino Fraga Filho Hospital, Institute of Thoracic Diseases, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
| | - Isabella Sued Leão
- Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
| | - Bianca do Carmo Schorr
- Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
| | - José Miguel Luz Parente
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Piauí, Piauí 64049-550, Brazil
| | - Daniela Calado Lima
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Piauí, Piauí 64049-550, Brazil
| | - Eduardo Santos Silveira Júnior
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Piauí, Piauí 64049-550, Brazil
| | - Genoile Oliveira Santana Silva
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Roberto Santos General Hospital (HGRS) of the Bahia State Department of Health, Bahia 40110-060, Brazil
| | - Neogélia Pereira Almeida
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Roberto Santos General Hospital (HGRS) of the Bahia State Department of Health, Bahia 40110-060, Brazil
| | - Andrea Vieira
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Irmandade Santa Casa da Misericórdia of São Paulo, São Paulo 01221020, Brazil
| | - Maria Luiza Queiroz de Bueno
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Irmandade Santa Casa da Misericórdia of São Paulo, São Paulo 01221020, Brazil
| | - Júlio Maria Chebli
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Juiz de Fora, Minas Gerais 36036-247, Brazil
| | - Érika Ruback Bertges
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Juiz de Fora, Minas Gerais 36036-247, Brazil
| | - Luísa Martins da Costa Brugnara
- Division of Gastroenterology, Department of Internal Medicine, Hospital University, Faculty of Medicine, Federal University of Juiz de Fora, Minas Gerais 36036-247, Brazil
| | - Columbano Junqueira Neto
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Federal District Base Hospital, Brasília 70330-150, Brazil
| | - Stefania Burjack Gabriel Campbell
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Federal District Base Hospital, Brasília 70330-150, Brazil
| | - Luana Letiza Discacciati
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Federal District Base Hospital, Brasília 70330-150, Brazil
| | - João Paulo Silva Cézar
- Division of Gastroenterology, Inflammatory Bowel Disease Outpatient Clinic, Federal District Base Hospital, Brasília 70330-150, Brazil
| | - Tiago Nunes
- Gastrointestinal Physiology, Institute of Nutritional Science, Nestle Research Center, Lausanne 1000, Switzerland
| | - Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary T2N4Z6, Canada
| | - Cyrla Zaltman
- Division of Gastroenterology, Department of Internal Medicine, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21940-230, Brazil
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Penhasi A, Gomberg M, Shalev DE. A novel nicotine pectinate salt formulated in a specific time-controlled delivery system: A new approach for colon-targeted nicotine release. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Jones DP, Richardson TG, Davey Smith G, Gunnell D, Munafò MR, Wootton RE. Exploring the Effects of Cigarette Smoking on Inflammatory Bowel Disease Using Mendelian Randomization. CROHN'S & COLITIS 360 2020; 2:otaa018. [PMID: 33506196 PMCID: PMC7809707 DOI: 10.1093/crocol/otaa018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Previous observational evidence has suggested an association between smoking and inflammatory bowel disease (IBD). METHODS We used observational techniques followed by Mendelian randomization to explore whether smoking is a causal factor in the development of IBD and its subtypes. RESULTS In those who have ever smoked, we observed increased risk of IBD and, in current smokers, we observed increased risk of Crohn disease and decreased risk of ulcerative colitis. However, our Mendelian randomization analyses found little evidence that smoking affects the development of IBD. CONCLUSION Overall, our results suggest that smoking does not causally influence the risk of IBD.
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Affiliation(s)
- Daniel P Jones
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Southmead Hospital, Westbury-on-Trym, Bristol, UK
| | - Tom G Richardson
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit, Bristol, UK
| | - George Davey Smith
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
| | - David Gunnell
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
| | - Marcus R Munafò
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
- UK Centre for Tobacco and Alcohol Studies, University of Bristol, Bristol, UK
- School of Psychological Science, University of Bristol, Bristol, UK
| | - Robyn E Wootton
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
- School of Psychological Science, University of Bristol, Bristol, UK
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Rivera NV, Patasova K, Kullberg S, Diaz-Gallo LM, Iseda T, Bengtsson C, Alfredsson L, Eklund A, Kockum I, Grunewald J, Padyukov L. A Gene-Environment Interaction Between Smoking and Gene polymorphisms Provides a High Risk of Two Subgroups of Sarcoidosis. Sci Rep 2019; 9:18633. [PMID: 31819081 PMCID: PMC6901455 DOI: 10.1038/s41598-019-54612-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 11/13/2019] [Indexed: 12/13/2022] Open
Abstract
The influence and effect of cigarette smoking in sarcoidosis is unclear. Here, we evaluated gene-environment interaction between multiple genetic variants including HLA genes and smoking in sarcoidosis defined by two clinical phenotypes, Löfgren's syndrome (LS) and patients without Löfgren's syndrome (non-LS). To quantify smoking effects in sarcoidosis, we performed a gene-environment interaction study in a Swedish population-based case-control study consisting of 3,713 individuals. Cases and controls were classified according to their cigarette smoking status and genotypes by Immunochip platform. Gene-smoking interactions were quantified by an additive interaction model using a logistic regression adjusted by sex, age and first two principal components. The estimated attributable proportion (AP) was used to quantify the interaction effect. Assessment of smoking effects with inclusion of genetic information revealed 53 (in LS) and 34 (in non-LS) SNP-smoking additive interactions at false discovery rate (FDR) below 5%. The lead signals interacting with smoking were rs12132140 (AP = 0.56, 95% CI = 0.22-0.90), p = 1.28e-03) in FCRL1 for LS and rs61780312 (AP = 0.62, 95% CI = 0.28-0.90), p = 3e-04) in IL23R for non-LS. We further identified 16 genomic loci (in LS) and 13 (in non-LS) that interact with cigarette smoking. These findings suggest that sarcoidosis risk is modulated by smoking due to genetic susceptibility. Therefore, patients having certain gene variants, are at a higher risk for the disease. Consideration of individual's genetic predisposition is crucial to quantify effects of smoking in sarcoidosis.
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Affiliation(s)
- Natalia V Rivera
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
| | - Karina Patasova
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Susanna Kullberg
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Lina Marcela Diaz-Gallo
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Tomoko Iseda
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Camilla Bengtsson
- Institute of Environmental Medicine (IMM), Karolinska Institutet, SE-171 77, Stockholm, Sweden
| | - Lars Alfredsson
- Institute of Environmental Medicine (IMM), Karolinska Institutet, SE-171 77, Stockholm, Sweden
| | - Anders Eklund
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Ingrid Kockum
- Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, SE-171 76, Stockholm, Sweden
| | - Johan Grunewald
- Division of Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
| | - Leonid Padyukov
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden
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Chen D, Xiao C, Jin H, Yang B, Niu J, Yan S, Sun Y, Zhou Y, Wang X. Exposure to atmospheric pollutants is associated with alterations of gut microbiota in spontaneously hypertensive rats. Exp Ther Med 2019; 18:3484-3492. [PMID: 31602224 PMCID: PMC6777218 DOI: 10.3892/etm.2019.7934] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 05/28/2019] [Indexed: 12/12/2022] Open
Abstract
Atmospheric particulate matter with a diameter <2.5 µm (PM2.5) and pollution are worldwide environmental problems and may have negative effects on cardiovascular disease through the lung and gut. The dynamics of intestinal microflora in response to particulate pollutants is unclear. The present study investigated changes in the gut microbiota related to pollutant exposure using spontaneously hypertensive rats (SHR). DNA was extracted from fecal samples. Amplicon Generation and the quality control of PCR products were performed. PCR products was sequenced on an Illumina HiSeq 2500 platform. Data analysis included: operational taxonomic unit (OTU) clustering and species annotation, alpha diversity, beta diversity, principal coordinates analysis (PCoA), and the use of PICRUSt bioinformatics software. The microbial diversity of the SHR rats was inversely associated with exposure to pollutants. In terms of relative abundance, 24 bacterial genera and 2 genera in particular (Actinobacillus and Fusobacterium) significantly declined, and one genus (Treponema) increased. Moreover, pollutant exposure was associated with the accumulation of genes from the gut microbiota that are implicated in cardiovascular diseases. From the long-term exposure experiment, rats appeared to respond to pollutant injury. In conclusion, these results suggest that the effects of atmospheric pollutants on organisms are not limited to the respiratory tract, but also include the gastrointestinal tract. Pollutants are likely to influence the intestinal microbiota and promote the progression of cardiovascular disease.
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Affiliation(s)
- Dongmei Chen
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Chunling Xiao
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Huanrong Jin
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Biao Yang
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jiayu Niu
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Siyuan Yan
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Ye Sun
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yuan Zhou
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xiangming Wang
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
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48
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Lee HS, Kim K, Jung S, Hong M, Kim BM, Yoo DS, Moon JW, Baek J, Hwang SW, Park SH, Yang SK, Han B, Song K, Ye BD. Effects of smoking on the association of human leukocyte antigen with ulcerative colitis. J Gastroenterol Hepatol 2019; 34:1777-1783. [PMID: 31038770 DOI: 10.1111/jgh.14695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 04/16/2019] [Accepted: 04/17/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Tobacco smoking is a risk factor for gastrointestinal disorders, causing mucosal damage and impairing immune responses. However, smoking has been found to be protective against ulcerative colitis (UC). Human leukocyte antigen (HLA) is a major susceptibility locus for UC, and HLA-DRB1*15:02 has the strongest effect in Asians. This study investigated the effects of smoking on the association between HLA and UC. METHODS The study enrolled 882 patients with UC, including 526 never, 151 current, and 205 former smokers, and 3091 healthy controls, including 2124 never, 502 current, and 465 former smokers. Smoking-stratified analyses of HLA data were performed using a case-control approach. RESULTS In a case-control approach, HLA-DRB1*15:02 was associated with UC in never smokers (ORnever smokers = 3.20, Pnever smokers = 7.88 × 10-23 ) but not in current or former smokers (Pcurrent smokers = 0.72 and Pformer smokers = 0.33, respectively). In current smokers, HLA-DQB1*06 was associated with UC (ORcurrent smokers = 2.59, Pcurrent smokers = 6.39 × 10-12 ). No variants reached genome-wide significance in former smokers. CONCLUSIONS An association between UC and HLA-DRB1*15:02 was limited to never smokers. Our findings highlight that tobacco smoking modifies the effects of HLA on the risk of UC.
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Affiliation(s)
- Ho-Su Lee
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kihyun Kim
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seulgi Jung
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Myunghee Hong
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byoung Mok Kim
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae-Sung Yoo
- Division of Veterinary Epidemiology, Animal and Plant Quarantine Agency, Ministry of Agriculture Food and Rural Affair, Gimcheon, Republic of Korea
| | - Jung Won Moon
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jiwon Baek
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung Wook Hwang
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Buhm Han
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyuyoung Song
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Park S, Chun J, Han KD, Soh H, Kang EA, Lee HJ, Im JP, Kim JS. Dose-response relationship between cigarette smoking and risk of ulcerative colitis: a nationwide population-based study. J Gastroenterol 2019; 54:881-890. [PMID: 31093771 DOI: 10.1007/s00535-019-01589-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Former cigarette smokers are at risk of developing ulcerative colitis (UC). However, the impact of smoking behavior on the occurrence of UC according to the amount smoked remains elusive. We aimed to determine the relationship between smoking behavior and the risk of UC development. METHODS We conducted a retrospective population-based cohort study using the National Health Insurance Service database in South Korea. From January 2009 to December 2012, 23,235,771 individuals over 18 years of age who underwent a national health examination were enrolled and followed until 2016. All study participants were divided into the following 3 groups: nonsmokers, former smokers, and current smokers. The primary endpoint was newly developed UC. RESULTS Compared with nonsmokers, the risk of UC development was significantly higher in former smokers [adjusted hazard ratio (aHR) 1.83; 95% confidence interval (CI) 1.73-1.95] but significantly lower in current smokers (aHR 0.92; 95% CI 0.87-0.98). Among current smokers, individuals who stopped smoking after the baseline evaluation had a significantly higher risk of UC development than those who continued to smoke (aHR 2.42; 95% CI 2.10-2.80). The risk of UC development among former smokers was significantly associated with smoking amount and duration. Among current smokers, however, the risk of UC development was not correlated with the cumulative lifetime smoking exposure. The preventive effect of current smoking on UC development was observed only in men (aHR 0.90; 95% CI 0.84-0.96). CONCLUSIONS Compared with nonsmokers, former smokers have a significantly higher risk of UC development that may be proportional to the cumulative smoking exposure.
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Affiliation(s)
- Seona Park
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea.
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 20, Eonju-ro 63-gil, Gangnam-gu, Seoul, 06229, South Korea.
| | - Kyung-Do Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Hosim Soh
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
| | - Eun Ae Kang
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
| | - Hyun Jung Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
| | - Jong Pil Im
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul, 03080, South Korea
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50
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Mogilevski T, Burgell R, Aziz Q, Gibson PR. Review article: the role of the autonomic nervous system in the pathogenesis and therapy of IBD. Aliment Pharmacol Ther 2019; 50:720-737. [PMID: 31418887 DOI: 10.1111/apt.15433] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 04/25/2019] [Accepted: 07/01/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is a growing body of evidence implicating a role for the brain-gut axis in the pathogenesis of inflammation in patients with IBD. AIMS To perform a narrative review of published literature regarding the association of the autonomic nervous system and intestinal inflammation and to describe the rationale for and emerging use of autonomic manipulation as a therapeutic agent METHODS: Current relevant literature was summarised and critically examined. RESULTS There is substantial pre-clinical and clinical evidence for a multifaceted anti-inflammatory effect of the vagus at both systemic and local intestinal levels. It acts via acetylcholine-mediated activation of α-7-acetylcholine receptors involving multiple cell types in innate and adaptive immunity and the enteric nervous system with subsequent protective influences on the intestinal barrier, inflammatory mechanisms and the microbiome. In patients with IBD, there is evidence for a sympatho-vagal imbalance, functional enteric neuronal depletion and hyporeactivity of the hypothalamic-pituitary-adrenal axis. Direct or transcutaneous vagal neuromodulation up-regulates the cholinergic anti-inflammatory pathway in pre-clinical and clinical models with down-regulation of systemic and local intestinal inflammation. This is supported by two small studies in Crohn's disease although remains to be investigated in ulcerative colitis. CONCLUSIONS Modulating the cholinergic anti-inflammatory pathway influences inflammation both systemically and at a local intestinal level. It represents a potentially underutilised anti-inflammatory therapeutic strategy. Given the likely pathogenic role of the autonomic nervous system in patients with IBD, vagal neuromodulation, an apparently safe and successful means of increasing vagal tone, warrants further clinical exploration.
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Affiliation(s)
- Tamara Mogilevski
- Centre for Neuroscience, Surgery and Trauma, Barts and the London School of Medicine and Dentistry, Blizard Institute, Wingate Institute of Neurogastroenterology, London, UK.,Barts Health NHS Trust, London, UK.,Department of Gastroenterology, Monash University and Alfred Health, Melbourne, Australia
| | - Rebecca Burgell
- Department of Gastroenterology, Monash University and Alfred Health, Melbourne, Australia
| | - Qasim Aziz
- Centre for Neuroscience, Surgery and Trauma, Barts and the London School of Medicine and Dentistry, Blizard Institute, Wingate Institute of Neurogastroenterology, London, UK.,Barts Health NHS Trust, London, UK
| | - Peter R Gibson
- Department of Gastroenterology, Monash University and Alfred Health, Melbourne, Australia
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