IBD Study Archives

Below are a series of previous IBD studies from the past years. Please scroll down to see a sample of them.

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The Manitoba IBD Cohort Study

 

Psychological functioning and quality of life

Graff LA, Walker JR, Bernstein CN Depression and anxiety in inflammatory bowel disease: a review of comorbidity and managementInflammatory Bowel Disease 2009; 15:1105-18.

This report reviews in depth the most recent clinical knowledge regarding mood and anxiety disorders in IBD including how commonly they occur,  other psychological factors in IBD, and treatment of psychological disorders in patients with IBD, considering both medication and psychotherapy options.

Tache Y, Bernstein CN. The role for the brain-gut axis in inflammatory bowel disease: Is  depression cause and effect? Gastroenterology 2009; 136: 2058-61.

This editorial was written to accompany an important research paper from McMaster University where investigators used a mouse model to show that depression could exacerbate colitis and that treatment of depression could improve both depression and colitis. Dr Tache, who coauthored the editorial, is a world renowned expert in animal models of inflammation and I drew on some of our findings from the Cohort Study that draw attention to the importance of patients psychological well being in terms of their quality of life and physical health

Graff LA, Walker JR, Clara I, Miller N, Rogala L, Rawsthorne P, Bernstein CN. Stress coping, distress, and health perceptions in inflammatory bowel disease and community controlsAmerican Journal of Gastroenterology 2009; 104: 2959-69.

We looked at distress levels and coping approaches to stress, comparing those with IBD to people in the general community who don’t have IBD.  People with active IBD were more likely to experience psychological challenges, including higher distress, a lower sense of well-being, and less of a sense of life control (often called mastery), compared to those without IBD.  They were also more likely to use strategies for coping with stress that are not as helpful such as avoiding others and self-blame.  When the IBD was not active for an extended period of time (we measured 6 months), then those individuals managed very similarly to people without IBD  However, those with  IBD had a more pessimistic view of their health compared to people in the community even though the individuals in the community often had other health problems.

Disease activity 

Clara I, Lix LM, Walker JR, Graff LA, Miller N, Rogala L, Rawsthorne P, Bernstein CN. The Manitoba IBD Index: Evidence for a New and Simple Indicator of  IBD ActivityAmerican Journal of Gastroenterology 2009; 104: 1754-63.

In this study we developed a single question scale asking people how active their symptoms were over the prior 6 months, and then validated this measure against other longer, more widely-used scales of disease activity. This single question is a straightforward way to get a good picture of their experience with IBD over a longer period than is usually considered, and can be used to categorize active disease or inactive disease over the previous 6 months. This type of activity index is important in the conduct of studies such as our Manitoba IBD Cohort Study that follow people over a long period of time. We expect that others will also be using this index in other cohort studies around the world.

 

Irritable bowel syndrome in IBD

Our goal was to determine how common the diagnosis of irritable bowel syndrome is a sample of IBD patients.

Burgmann T, Clara I, Graff L, Walker J, Lix L, Rawsthorne P, McPhail C, Rogala L, Miller N, Bernstein CN.The Manitoba IBD Cohort study: Prolonged symptoms before diagnosis-How much is IBS? Clinical Gastroenterology and Hepatology 2006; 4: 614-20.

Irritable bowel syndrome is a disorder affecting up to 15% of the general population. It is manifested by abdominal pain with diarrhea or constipation. It is not associated with any inflammation and there are no specific diagnostic tests that can clinch a diagnosis of irritable bowel syndrome. Because it is so common (at least 15x more common that IBD) it stands to reason that some patients with IBD may also have irritable bowel syndrome. Clinicians often are faced with the decision as to whether patients with IBD may at times have complaints that are not secondary to their IBD but rather to irritable bowel. In a study conducted using data from our Manitoba IBD Cohort Study we were able to estimate (on a population-basis) that approximately 14% of Manitobans with IBD may have irritable bowel syndrome that precedes their diagnosis of IBD. Hence irritable bowel syndrome is no more common in IBD than the general population, but on the other hand, at times some patients whose IBD is not active may have symptoms that are secondary to an irritable bowel rather than an inflamed one.


Our goal was to determine if patients with IBD are any more or less likely to have impaired psychological function, quality of life or actual psychiatric illness compared to persons in the general population without IBD and whether there are predictors within the IBD population of adverse outcomes in regards to these issues.

Graff LA, Walker JR, Lix L, Clara I, Rawsthorne P, Rogala L, Miller N, Jakul L, McPhail C, Ediger J, Bernstein CN. The relationship of inflammatory bowel disease type and activity to psychological functioning and quality of life. Clinical Gastroenterology and Hepatology 2006; 4:1491-1501.

There has long been an assumption that patients with Crohn’s disease and ulcerative colitis can be differentiated not only by disease presentation and markers, but also by their psychological functioning. We aimed to assess the relationship of both disease type and activity to clarify the relationship with psychological functioning and quality of life. We found that those with active disease had higher levels of distress, health anxiety, and perceived stress, lower social support, well-being and mastery, and poorer disease-specific quality of life, relative to those with inactive disease. Disease type (Crohn’s disease versus ulcerative colitis) did not contribute to psychological functioning or quality of life. Those with either active or inactive disease (and hence any subject with either form of IBD) had suboptimal general quality of life. However, Crohn’s disease and ulcerative colitis were not differentiated in their psychological profiles. Disease activity rather than disease subtype is a key factor, highlighting the need for clinicians to assess their patients’ functioning beyond the usual IBD symptom focus to include psychological health.

FINDINGS FROM THE MANITOBA IBD RISK FACTOR STUDY

Bernstein CN, Rawsthorne, P, Cheang M, Blanchard JF. A population-based case control study of potential risk factors for IBD. American Journal of Gastroenterology 2006; 101(5):993-1002.

In this report we identified the personal and lifestyle factors most strongly associated with IBD. In Crohn’s disease they were: 1) being Jewish, 2) having a relative with a diagnosis of IBD, 3) being a smoker. In ulcerative colitis they were: 1) being Jewish, 2) having a relative with a diagnosis of IBD and 3) being an ex-smoker. Smoking is bad for either Crohn’s disease or ulcerative colitis in that both groups of patients are more likely to have ever smoked compared to the general population. However, ulcerative colitis patients are more likely to be ex-smokers. So DO NOT START SMOKING; it could help reduce your risk of getting IBD. You can’t change your circumstance as to where you were born, what diseases your family members have or what your ethnicity is, but you can change this lifestyle factor. No one understands what component of smoke would contribute to developing IBD, or if in the case of Crohn’s disease it is that smoking modifies the disease once it is initiated. It is known that SMOKERS HAVE WORSE OUTCOMES OF CROHN’S DISEASE THAN NON-SMOKERS. In this same study we also found several factors that seemed protective against getting Crohn’s disease. These included: 1) having pet cats before age 5, 2) being born to new immigrants to Canada-that is being a first generation Canadian, and 3) having a large family with increased number of siblings.

Genetics of IBD

Brant S, Wang M-H, Rawsthorne P, Sargent M, Datta LW, Nouvet F, Shugart YY, Bernstein CN. A population-based case control study of CARD15 and other risk factors in Crohn’s disease and ulcerative colitis. American Journal of Gastroenterology 2007; 102: 313-23.

A number of studies since 2001 have reported that mutations in the NOD-2 gene on chromosome 16 is associated with an increased risk of Crohn’s disease. This study was the first population-based report on the risk posed by having a mutation in the NOD-2 gene. Being population-based means we have drawn our data from subjects representing the whole population and not just from a specialty referral clinic. Together with researchers from Johns Hopkins University, we reported that having a NOD-2 mutation accounted for approximately 25% of subjects with Crohn’s disease. Further, having a mutation increased the risk of getting Crohn’s disease 3-fold and having two mutations in the gene (humans have 2 copies of every gene in the body) increased the risk 40-fold. However, there are lots of people in the general population who have mutations in the NOD-2 gene and will never get Crohn’s disease; so having this mutation does not guarantee that the person will get Crohn’s disease. Also, there are lots of people (in fact about 70%) who have Crohn’s disease and don’t have the mutation. Hence, testing for this mutation is not currently offered as a means to determine risk for Crohn’s disease. Having a mutation in NOD-2 does not guarantee that you will get Crohn’s disease and not having a mutation in NOD-2 gene does not guarantee that you won’t get Crohn’s disease.

Kotlowski R, Bernstein CN, Silverberg MS, Krause DO. Population-based case-control study of alpha 1-antitrypsin and SLC11A1 in Crohn’s disease and ulcerative colitis. Inflammatory Bowel Disease 2008; 14:1112-7.

We aimed to determine if there are gene abnormalities for proteins that help in defense against bacteria in IBD. Our findings suggest that some patients with IBD may have an impairment in ability of their white blood cells to fend off certain bugs.

Is there an infectious cause of IBD?

For many years it has been suspected that a bug that causes a Crohn’s-like disease in cattle (Johne’s disease) may cause Crohn’s disease. This bug Mycobacterium paratuberculosis is difficult to find in humans. There have been a number of studies conducted in search of a possible association of Mycobacterium paratuberculosis with Crohn’s disease; some have been positive and some have been negative. This has become increasingly debated, but it is agreed by most involved in this research, that a major aspect lacking to advance our understanding in this area is a single, reproducible diagnostic test that can clinch the presence of Mycobacterium paratuberculosis with a high degree of certainty. Guessing that Mycobacterium paratuberculosis might be linked with Crohn’s disease has enormous implications for the beef and dairy industry of the entire world. So we should not guess. We should keep working towards understanding with certainty whether or not this infection is associated with Crohn’s disease.

Bernstein CN, Blanchard JF, Rawsthorne P, Collins MT. A population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn’s disease and ulcerative colitis. Journal of Clinical Microbiology 2004; 42:1129-1135.

In this study conducted with researchers at the University of Wisconsin we aimed to determine if people with Crohn’s disease were more likely to have an antibody response in their blood to Mycobacterium paratuberculosis. Such a response might indicate that the infection has been present at some time. Nearly 1000 blood samples were studied for these antibodies and approximately 35% of Manitobans were positive for these antibodies. However, there was no difference in rate of antibody positivity among persons with any of Crohn’s disease, ulcerative colitis or healthy controls. We are still uncertain if having an antibody response to this bug even proves that the infection has been present.


Bernstein CN, Nayar G, Hamel A, Blanchard JF. A pursuit of animal borne infections in the mucosa of subjects with inflammatory bowel disease and population-based controls. Journal of Clinical Microbiology 2003; 41:4986-90.

In this study the colon tissues of 25-30 subjects with each of Crohn’s disease, ulcerative colitis and healthy control volunteers were studied by the veterinarians of Manitoba (Agriculture Manitoba) to determine if the DNA of Mycobacterium paratuberculosis or other animal-borne infections was present in the colon. This study could not find any Mycobacterium paratuberculosis DNA in Crohn’s tissue, rarely in ulcerative colitis tissue and in about 25% of control tissue. This study concluded that there was no association between Mycobacterium paratuberculosis and Crohn’s disease.


FINDINGS FROM THE IBD EPIDEMIOLOGY DATABASE

Bernstein CN, Metge C, Blanchard JF, Yogendran M. Does the use of 5-aminosalicylates in inflammatory bowel disease prevent the development of colorectal cancer? American Journal of Gastroenterology 2003; 98: 2784-2788.

There has been much debate and discussion as to whether 5-ASA drugs (Asacol, Pentasa, Salofalk, Dipentum, and more recently Mezavant) if taken regularly could reduce the risk of developing colorectal cancer in patients with colitis. In this study we used our Database to extract all subjects who developed colorectal cancer between 1997-2000. We created a control group of IBD patients who did not develop colorectal cancer. We then linked these groups (IBD patients with and without colorectal cancer) to the provincial prescription drug program, DPIN which was initiated in 1995. We determined use of 5-ASA for at least 2 years prior to cancer diagnosis. We found no difference among those with cancer versus those without in terms of 5-ASA use. There have been about 6 other studies from other groups since then, assessing the possibility that 5-ASA may prevent against developing colorectal cancer and most have been negative. It is possible that 5-ASA may help to prevent colorectal cancer by keeping inflammation reduced, however, this remains unproven to date.


FINDINGS FROM THE IBD RESEARCH REGISTRY

The following are some of the other projects we have done through our Research Registry

Studies published in 2008-09

Moffatt D, Ilnyckyj A, Bernstein CN. A Population based study of breastfeeding iinflammatory bowel disease: Initiation, duration and effect on disease in the post partum periodAmerican Journal of Gastroenterology2009;  104: 2517-23.

We aimed to assess breastfeeding practices and the impact of breastfeeding on disease flare during the postpartum year in IBD. Women of childbearing age from 1985 to 2005 were identified from the University of Manitoba IBD Research Registry. Questionnaires were completed regarding pregnancy and the postpartum period. Data for initiation and duration of breastfeeding were compared with regional data from Manitobans. 132 women responded to the survey, yielding information on 156 births. Breastfeeding was initiated in 83.3% of women with IBD, 81.9% of Crohn’s disease patients, and 84.2% of ulcerative colitis patients vs. 77.1 % in the general population. 56.1% of women with IBD, breastfed for >24 weeks vs. 44.4% of non-IBD controls. The rate of disease flare in the postpartum year was not different in Crohn’s disease or UC among breastfeeders vs non breastfeeders. Risk of disease flare was not related to age at pregnancy, duration of disease, or socioeconomic status. We concluded that women with IBD are as likely as the general population to breastfeed their infants. Further, breastfeeding was not associated with an increased risk of disease flare and may even provide a protective effect against disease flare in the postpartum year. Women should be encouraged to breastfeed but must review whether it is safe to do so with their doctors, in terms of whether the medications they use cross into breast milk.

Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections or stress trigger flares in IBD?American Journal of Gastroenterology 2009; 104: 1298-1313

It is critical that we understand what might trigger flares of IBD and therefore what might patients be able to do or avoid, to avoid triggering flares. Non-steroidal anti-inflammatory drugs (NSAIDs which are drugs like Advil, Motrin, Naproxen), antibiotics, bowel or other infections, and stress have all been reported to be potential triggers of flares of IBD. In this review, we analyzed the medical literature that explores these associations. There is some evidence to support an association between NSAID use and flares but little data to associate antibiotic use directly with flares. An important connection between antibiotic use and an exacerbation of symptoms is through the development of Clostridium difficile infections (this infection causes colitis). There is little evidence that other non bowel infections trigger flares of IBD. Although there is strong evidence for an association between perceived stress levels and flares, there is a weaker association between a simple accounting of stressful life events and flares. Much of the literature is limited by a lack of adequate control groups and failure to report on base rates in the population under study (i.e., NSAIDs and antibiotic use, occurrence of infections, and stress levels). More large population-based matched cohort or case crossover studies and a continued emphasis on prospective designs are needed to better explore these potential associations.


Older Studies

Tang L, Rawsthorne P, Bernstein CN. Are perineal and luminal fistulas associated in Crohn’s disease? A population-based study. Clinical Gastroenterology and Hepatology 2006; 4: 1130-4.

In this study we reviewed the manifestations of Crohn’s disease of the 1595 persons with Crohn’s disease in our Registry. We found that 398 reported having fistulas (tracks between the bowel and some other organ or the anus) or strictures. Of all those with fistulas 54% were anal only, 17% were anal and luminal (luminal fistula is between the bowel and some other bowel site or organ other than the anus), 28% were luminal only. There was a strong correlation between having an anal fistula and another type of fistula. Fistula patients were more likely to be diagnosed in younger ages, particularly in those presenting between 20-29 years. Compared with luminal fistulas, perianal fistulas had a higher likelihood to have colonic rather than isolated ileal involvement. The comparison of fistulizing Crohn’s disease to non-fistulizing disease revealed a predisposition to colonic, ileocolonic, and upper gastrointestinal disease versus isolated ileal involvement. This study reported a lower rate of fistulas in Crohn’s disease (up to 22%) than other studies that referral centres had previously reported.

Bernstein CN, Leslie WD, Taback S. Bone density in a population based cohort of premenopausal adult women with early-onset inflammatory bowel disease. American Journal of Gastroenterology 2003; 98:1094-100.

In this study we identified all women in our Registry who were diagnosed with IBD prior to age 20 and who were premenopausal at the time of the study. 70 women enrolled in the study and underwent nutritional survey and bone density testing. We found that the average bone density of these women was normal, and hence a being diagnosed with IBD as a child or teenager did not lead to increased rate of osteoporosis as adults. This, despite a high rate of steroid use as children in their IBD treatment.

Ilnyckyj A, Blanchard JF, Rawsthorne P, Bernstein CN. Perianal Crohn’s disease and pregnancy: Role of the mode of delivery. American Journal of Gastroenterology 1999; 94: 3274-3278.

In the first part of this study we linked our IBD Database with the Manitoba Labor and Delivery Database and found that women with IBD had a Cesarian Section rate of 21% while the general population Cesarian Section rate was 15%. The increased rate of Cesarian Section was the same for patients with ulcerative colitis as for patients with Crohn’s disease. Unless a women with ulcerative colitis has undergone a total colectomy with an ileoanal pouch procedure, there is no obvious reason why women with ulcerative colitis should have an increased rate of Cesarian Sections.

In the second part of the study we identified women in our Registry who were of childbearing age at any time after their diagnosis of Crohn’s disease and inquired as to who had pregnancies and we reviewed their mode of delivery. There were 52 women who had 64 pregnancies; 54 ended with vaginal delivery and 10 with Cesarian Section. 15 women had perineal disease (fistulas) prior to their vaginal deliveries. 4 of 15 had active perineal disease at time of delivery and all worsened after delivery. Of the 11 with inactive perineal disease at time of delivery, none had a flare of perineal disease within 1 year after delivery. There were 39 women without perineal disease at any time who had vaginal deliveries and within 1 year only 1 had a presentation of perineal fistula. Hence, we concluded that women with Crohn’s disease and active perineal disease should undergo Cesarian Section as mode of delivery. While women without active perineal disease at time of delivery could safely undergo vaginal delivery.


Cancer and IBD

Bernstein CN. Neoplasia in inflammatory bowel disease: surveillance and management strategies. Current Gastroenterology Reports 2006 Dec;8(6):513-8.

Bernstein CN. Natural history and management of flat and polypoid dysplasia in inflammatory bowel disease. Gastroenterology Clinics of North America 2006 Sep;35(3):573-9.

Bernstein CN, Kliewer E, Wajda A, Blanchard JF. The incidence of cancer among patients with IBD: A population-based study. Cancer 2001; 91: 854-862.

 

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