Original Contribution | Published:

Inflammatory Bowel Disease

A Prospective Population-Based Study of Triggers of Symptomatic Flares in IBD

The American Journal of Gastroenterology volume 105, pages 19942002 (2010) | Download Citation

Abstract

OBJECTIVES:

We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs).

METHODS:

Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed.

RESULTS:

A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare.

CONCLUSIONS:

This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.

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References

  1. 1.

    , . Psychological factors. In: Bernstein C (ed). The Inflammatory Bowel Disease Yearbook, Vol 4. 2007. Remedica: London, UK.

  2. 2.

    , , . Utilization of health care resources by individuals with inflammatory bowel disease in the US: a profile of time since diagnosis. Am J Gastroenterol 2004;99:650–655.

  3. 3.

    , , . The 10 remaining mysteries of inflammatory bowel disease. Gut 2008;57:429–433.

  4. 4.

    , . Non-steroidal anti-inflammatory drugs, aspirin and newly diagnosed colitis: a case-control study. Aliment Pharmacol Ther 2003;17:817–825.

  5. 5.

    , , et al. Clostridium difficile and inflammatory bowel disease. Gut 1983;24:713–717.

  6. 6.

    , , et al. Acute viral enteritis and exacerbations of inflammatory bowel disease. Gastroenterology 1982;83:1207–1209.

  7. 7.

    , . Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut 2006;55:1053–1054.

  8. 8.

    , , . Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol 2009;104:1298–1313.

  9. 9.

    , , . A unifying hypothesis for the mechanism of NSAID related gastrointestinal toxicity. Ann Rheum Dis 1996;55:211–213.

  10. 10.

    , . Use of antibiotics in the treatment of inflammatory bowel disease. Inflamm Bowel Dis 2006;12:651–664.

  11. 11.

    , . Update on Clostridium difficile associated disease. Curr Opin Gastroenterol 2007;23:4–9.

  12. 12.

    , , et al. Prevalence of diarrhea at a university hospital and association with modifiable risk factors. Ann Pharmacother 2006;40:1030–1034.

  13. 13.

    , , . Excess hospitalization burden associated with Clostridium difficile in patients with Inflammatory Bowel disease. Gut 2008;57:205–210.

  14. 14.

    , , et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:345–351.

  15. 15.

    , , et al. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:339–344.

  16. 16.

    , , et al. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008;103:1443–1450.

  17. 17.

    . Inflammatory bowl disease. N Engl J Med 2002;347:417–429.

  18. 18.

    . Microbial influences in inflammatory bowel diseases. Gastroenterology 2008;134:577–594.

  19. 19.

    , , et al. Inflammatory bowel disease: patients’ beliefs bout the etiology of their disease—a controlled study. Psychosom Med 1993;55:131–139.

  20. 20.

    , , et al. Lag time between stress events and risk of recurrent episodes of inflammatory bowel disease. Epidemiology 1991;2:141–145.

  21. 21.

    , , et al. Stress and exacerbation in ulcerative colitis: A prospective study of patients enrolled in remission. Am J Gastroenterol 2000;95:1213–1220.

  22. 22.

    , , et al. Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study. Am J Gastroenterol 2003;98:2203–2208.

  23. 23.

    , , et al. Predicting relapse in Crohn's disease: a biopsychosocial model. Gut 2008;57:1386–1392.

  24. 24.

    . Stress and the Gastrointestinal Tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance. Am J Physiol Gastrointest Liver Physiol 2001;280:G315–G319.

  25. 25.

    , , . Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol 2002;21:531–541.

  26. 26.

    , , et al. Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? Psychosom Med 2004;66:215–223.

  27. 27.

    . The Pittsburgh common cold studies: psychosocial predictors of susceptibility to respiratory infectious illness. Internat J Behav Med 2005;12:123–131.

  28. 28.

    , , et al. Childhood socioeconomic status and host resistance to infectious illness in adulthood. Psychosom Med 2004;66:553–558.

  29. 29.

    , , et al. Do early-life events permanently alter behavioral and hormonal responses to stressors? Intern J Dev Neurosci 1998;16:149–164.

  30. 30.

    . Social relationships and health. Am Psychol 2004;59:676–684.

  31. 31.

    , , et al. Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza a virus. Psychosom Med 2006;68:809–815.

  32. 32.

    , , et al. Epidemiology of Crohn's disease and ulcerative colitis in a central Canadian province: a population-based study. Am J Epidemiol 1999;149:916–924.

  33. 33.

    , . Hearsay: Is patient self-report of health care utilization accurate? Gastroenterology 2008;134:A498.

  34. 34.

    , , et al. The Manitoba IBD Index: evidence for a new and simple indicator of IBD activity. Am J Gastroenterol 2009;104:1754–1763.

  35. 35.

    , , et al. A global measure of perceived stress. J Health Soc Behav 1983;24:385–396.

  36. 36.

    , , . Development and validation of brief measures of positive and negative affect: The PANAS scales. J Pers Soc Psychol 1988;54:1063–1070.

  37. 37.

    , . The Positive and Negative Affect Schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample. Br J Clin Psychol 2004;43:245–265.

  38. 38.

    , , et al. Social ties and susceptibility to the common cold. JAMA 1997;277:1940–1944.

  39. 39.

    , , et al. Why do patients with ulcerative colitis relapse? Gut 1990;31:179–183.

  40. 40.

    , , . Analgesic ingestion and other factors preceding relapse in ulcerative colitis. Gut 1983;24:187–189.

  41. 41.

    , , et al. Antibiotic use and the risk of flare of inflammatory bowel disease. Clin Gastroenterol Hepatol 2005;3:459–465.

  42. 42.

    , . Inflammatory bowel disease and smoking: a review of epidemiology, pathophysiology, and therapeutic implications. Inflamm Bowel Dis 2004;10:848–859.

  43. 43.

    , , et al. Effects of active and passive smoking on disease course of Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2009;15:1199–1207.

  44. 44.

    , , et al. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ 2004;328:731–735.

  45. 45.

    , , et al. Health behaviours explain part of the differences in self reported health associated with partner/marital status in The Netherlands. J Epidemiol Commun Health 1995;49:482–488.

  46. 46.

    , , . Is there something unique about marriage? The relative impact of marital status, relationship quality, and network social support on ambulatory blood pressure and mental health. Ann Behav Med 2008;35:239–244.

  47. 47.

    , . Marriage and health: his and hers. Psychol Bull 2001;127:472–503.

  48. 48.

    , , et al. Stress, immune reactivity and susceptibility to infectious disease. Physiology Behavior 2002;77:711–716.

  49. 49.

    , , et al. Mucosally-directed adrenergic nerves and sympathomimetic drugs enhance non-intimate adherence of Escherichia coli 0157:H7 to porcine cecum and colon. Eur J Pharamcol 2006;539:116–124.

  50. 50.

    , , et al. Adrenergic modulation of Escherichia coli 0157:H7 adherence to the colonic mucosa. Am J Physiol 2004;287:G1238–G1246.

  51. 51.

    , . Adrenocorticotrophic hormone modulates Escherichia coli 0157:H7 adherence to porcine colonic mucosa. Stress 2005;8:185–190.

  52. 52.

    , , et al. Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by α2-adrenoreceptors in the presence of experimental colitis. Br J Pharmacol 2003;139:309–320.

  53. 53.

    , , et al. Inverse regulation of alpha and beta adrenoreceptor during trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor function of non-inflamed rat gastric fundus. Neurogastroenterol Motil 2001;13:339–344.

  54. 54.

    , , . Inflammation and its discontent: the role of cytokines in the pathophysiology of major depression. Biol Psychiatr 2009;65:732–741.

  55. 55.

    , , et al. The role of the sympathetic nervous system in intestinal inflammation. Gut 2006;55:1640–1649.

  56. 56.

    , . Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment. Biol Psychiatry 2001;49:391–404.

  57. 57.

    , , et al. Impaired synthesis or cellular storage of norepinephrine, dopamine and 5-hydroxytryptamine in human inflammatory bowel disease. Dig Dis Sci 2002;47:216–224.

  58. 58.

    , , et al. Decreased availability of intestinal dopamine in transmural colitis may relate to inhibitory effects of interferon-gamma upon L-DOPA uptake. Acta Physiol Scand 2004;180:379–386.

  59. 59.

    . Enetric α2-adrenoreceptors: pathophysiological implications in functional and inflammatory bowel disorders. Neurochem International 2007;51:282–288.

  60. 60.

    , , et al. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol 2008;103:162–169.

  61. 61.

    , , et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. Clin Gastroenterol Hepatol 2008;6:1218–1224.

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Author information

Affiliations

  1. IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

    • Charles N Bernstein
    • , Sunny Singh
    • , Lesley A Graff
    • , John R Walker
    • , Norine Miller
    •  & Mary Cheang
  2. Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    • Charles N Bernstein
  3. Department of Clinical Health Psychology, University of Manitoba, Winnipeg, Manitoba, Canada

    • Lesley A Graff
    •  & John R Walker

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Competing interests

Guarantor of the article: Charles N. Bernstein, MD.

Specific author contributions: Study concept and design; analysis and interpretation of data; drafting of the paper; critical revision of the paper for important intellectual content; statistical analysis; obtained funding; technical or material support; study supervision: Charles N. Bernstein; acquisition of data; analysis and interpretation of data; critical revision of the paper for important intellectual content: Sunny Singh; study concept and design; analysis and interpretation of data; drafting of the paper; critical revision of the paper for important intellectual content; statistical analysis; study supervision: Lesley A. Graff; study concept and design; analysis and interpretation of data; drafting of the paper; critical revision of the paper for important intellectual content; statistical analysis: John R. Walker; acquisition of data; critical revision of the paper for important intellectual content; technical or material support: Norine Miller; analysis and interpretation of data; critical revision of the paper for important intellectual content; statistical analysis: Mary Cheang.

Financial support: Charles Bernstein is supported in part by a Research Scientist Award of the Crohn's and Colitis Foundation of Canada and holds the Bingham Chair in Gastroenterology. This study was sponsored in part by UCB Canada.

Potential competing interests: In the past year Dr Bernstein has served as a consultant to or on the advisory boards of Shire Canada and Abbott Canada and has received research funding from UCB Canada. The other authors declare no conflict of interest.

Corresponding author

Correspondence to Charles N Bernstein.

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DOI

https://doi.org/10.1038/ajg.2010.140

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