Introduction Inflammatory Bowel Disease Research Articles

190 Functional Aspects of the Intestinal Microbiome in Inflammatory Bowel Disease

Introduction Inflammatory bowel disease (IBD) is associated with alterations in the interaction between resident microbes and the intestinal immune system. While shifts in microbial populations have been repeatedly shown in studies of the intestinal microbiome from IBD patients, potential confounding factors such as treatment or environmental exposures have not been fully accounted for. Furthermore, the functional implications of these microbial changes have not been determined. Material andMethods The composition of the microbiome from intestinal biopsies and stool samples were analyzed by 16S gene pyrosequencing. Gene and pathway composition were assessed from phylogenetically associated reference genomes. A novel combination of sparse linear modeling and factor analysis was used to associate microbial abundance, genes, metabolic modules, and pathways with disease and with environmental factors such as medications and smoking. Results We analyzed the GI microbiome of 119 patients with Crohn's disease (CD), 74 patients with ulcerative colitis (UC) and 27 healthy subjects (HS). In CD patients, Roseburia and Ruminococcus genus, respectively in the Lachnospiraceae and Ruminococcaceae families in the Firmicutes phylum, were less abundant. In CD patients with ileal involvement (iCD, n=43) specifically, sequences of the Ruminococcaceae family and of the Faecalibacterium genus in particular were reduced compared to other subjects. The only statistically significant feature specific to UC was the overrepresentation of Eggerthella genus (Actinobacteria phylum). Immunosuppressive treatment (azathioprine/6-mercaptopurine or anti-TNF agents) was associated with an increase of Escherichia/Shigella genus (Gammaproteobacteria), whereas mesalamine was associated with a decrease of Gammaproteobacteria. Genes involved in genetic information processing, nucleic acid metabolism and biosynthesis, amino acid metabolism and methane oxidation were significantly less abundant in IBD patients than in HS. Lipid metabolism and catabolism modules were decreased in iCD. Conversely, genes involved in nitrogen and sulfur metabolism, cysteine metabolic process and in some amino acid transport systems (complementing reductions in their metabolism) were overrepresented in IBD. In iCD specifically, genes involved in carbohydrate metabolism, metabolisms of cofactors and vitamins, and virulence factors were more abundant. Conclusion IBD and iCD in particular are associated with a dysbiosis characterized by changes in Firmicutes, Proteobacteria and Actinobacteria phyla. Environmental factors and, importantly, treatments are associated with independent changes in the GI microbiome. These modest perturbations in bacterial composition are in turn associated with major perturbations of GI microbiome function with potential impact on the host.

Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study

IntroductionInflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are similar chronic inflammatory diseases whose definitive etiology is unknown. Following recent clinical and genetic evidence supporting an intertwined pathogenic relationship, we conducted a pilot study to measure fecal calprotectin (fCAL) and IBD-related serologies in AS patients.MethodsConsecutive AS patients were recruited from a long-term prospectively collected longitudinal AS cohort at Cedars-Sinai Medical Center. Controls were recruited from Cedars-Sinai Medical Center employees or spouses of patients with AS. Sera were tested by ELISA for IBD-associated serologies (antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibody IgG and IgA, anti-I2, anti-OmpC, and anti-CBir1). The Bath Ankylosing Spondylitis Disease Activity Index, the Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Radiology Index were completed for AS patients.ResultsA total of 81 subjects (39 AS patients and 42 controls) were included for analysis. The average age of AS patients was 47 years and the average disease duration was 22 years. AS patients were predominantly male; 76% were HLA-B27-positive. Median fCAL levels were 42 μg/g and 17 μg/g in the AS group and controls, respectively (P < 0.001). When using the manufacturer's recommended cutoff value for positivity of 50 μg/g, stool samples of 41% of AS patients and 10% of controls were positive for fCAL (P = 0.0016). With the exception of ANCA, there were no significant differences in antibody levels between patients and controls. Median ANCA was 6.9 ELISA units in AS patients and 4.3 ELISA units in the controls. Among AS patients stratified by fCAL level, there were statistically significant differences between patients and controls for multiple IBD-associated antibodies.ConclusionCalprotectin levels were elevated in 41% of patients with AS with a cutoff value for positivity of 50 μg/g. fCAL-positive AS patients displayed higher medians of most IBD-specific antibodies when compared with healthy controls or fCAL-negative AS patients. Further studies are needed to determine whether fCAL can be used to identify and characterize a subgroup of AS patients whose disease might be driven by subclinical bowel inflammation.

A chronic care model significantly decreases costs and healthcare utilisation in patients with inflammatory bowel disease

IntroductionInflammatory bowel disease (IBD) is a chronic condition, yet the model of care is often reactive. We sought to examine whether a formal IBD service (IBDS) reduced inpatient healthcare utilisation or lowered costs for inpatient care. Material and methodsWith protocols, routine nurse phone follow-up a help-line, more proactive care was delivered, with many symptoms and concerns dealt with prior to routine presentation. Over two five month periods before (2007/8) and after (2009/10) introducing a formal IBDS two discrete cohorts of admitted IBD patients were identified at a single centre. Each patient was assigned five contemporaneously admitted, age and gender matched controls. Inpatient healthcare utilisation was compared between patients and controls and disease-specific factors amongst the two IBD cohorts. ResultsThe initial audit captured 102 admitted IBD patients (510 controls, median age 44years, 57% female); the second audit 95 patients (475 controls, median age 46years, 45.3% female). In 2009/10, the number of admissions was lower in IBD patients than in controls (mean 1.53+/−1.03 vs. 2.54+/−2.35; p<0.0001). This contrasts with the first audit, where IBD patients had more admissions than controls. Following IBDS introduction, the mean total cost of inpatient care was lower for IBD patients than controls (US$12,857.48 (US$15,236.79) vs. US$ 30,467.78 (US$ 53,760.20), p=0.005). In addition, patients known to a specialist gastroenterologist (GE) and the IBD Service tended to have the lowest mean number of admissions (GE and IBDS 1.14 (+/−0.36) vs. no GE/IBDS 1.64 (+/−1.25)). ConclusionsHealthcare utilisation and disease burden in IBD decreased significantly since introducing an IBDS. These data suggest that proactive management improved outcomes. Contact with a gastroenterologist and IBDS seemed to give best results.

Inflammatory bowel disease, drug therapy and pregnancy: awareness in female IBD patients of reproductive age

IntroductionInflammatory bowel disease (IBD) often affects women during their child bearing age. Management of a pregnant IBD patient or any women contemplating pregnancy poses unique challenge. Patient understanding of the...

W09-03 - Associations of affective disorder in patients with inflammatory bowel disease

IntroductionInflammatory Bowel Disease (IBD) is associated with co morbid depression and anxiety of up to 42%. Corticosteroids, used commonly in IBD, are known to cause psychiatric side-effects and could be an independent risk factor for affective illness. Recent studies show that depression is also associated with raised CRP and IL6.AimsThis study aims to show which demographic, clinical, medication and immunological factors are predictors of anxiety and depression in IBD.MethodsThe IBD, Steroids and Affective Disorder (ISA) study is a cross-sectional study of IBD patients in Edinburgh, UK. Out patients underwent assessment including Hospital Anxiety Depression Scale (HADS) past psychiatric history, steroid medication history, inflammatory markers, the Medication Adherence Rating Scale (MARS) and Altman Self Rated Mania Scale (ARSM).Results326 patients with Crohns and 256 with Colitis (72% of clinic attendees) were recruited. 251 (43%) patients scored 12 or above on the HADS questionnaire. 45% of patients had previously suffered from affective illness. Patients on Prednisolone and Budesonide scored significantly higher on HADS Depression (p = 0.03 and p = 0.002) as did those who had been on Prednisolone for more than 8 weeks (p = 0.041). Being on prednisolone was not associated with increased Colitis and Crohns activity indices (p = 0.2). HADS scores were measured against other disease and demographic variables.ConclusionAffective illness is common in the IBD population and the prescription and duration of systemic corticosteroids are associated with depression. Biological and disease variables may play an important role in co morbid affective illness in IBD

Massive per rectal bleeding following blunt abdominal trauma: First presentation of Crohn's disease

IntroductionInflammatory bowel disease is a chronic and relatively common disorder with heterogeneous presentation. Peak incidence occurs in the second and third decades of life. We present a patient with Crohn's disease whose first presentation was profuse bleeding/rectum following blunt abdominal trauma. presentation of caseA 29 year old previously healthy man presented one hour after sustaining relatively mild abdominal trauma, due to fall onto the ball during a rugby match. He complained of abdominal pain and one episode of large fresh rectal bleeding. He was pale and distressed with hypotension, tachycardia and abdominal guarding & fresh blood on digital rectal examination. With a provisional diagnosis of intestinal injury he was taken to theatre. Right hemi-colectomy was done for a thickened and inflamed segment of distal ileum, a large adjacent mesenteric haematoma & mesenteric lymph nodes and blood in distal bowel. Histology confirmed the features of Crohn's disease. discussionCrohn's disease is unusual cause of massive lower gastrointestinal bleeding occurring in 0.9–6% of patients. Rectal bleeding associated with diarrhoea is relatively more common than massive bleeding. The presence of Crohn's disease in young patients presenting like this is unlikely to be suspected and diagnosis could only be made after laparotomy.

M1032 Managing the Long Term Care of Inflammatory Bowel Disease Patients: the Cost to European Health Care Providers

Introduction Inflammatory Bowel Disease (IBD), which includes Crohn9s disease (CD) and Ulcerative Colitis (UC), is a chronic condition characterised by substantial morbidity. Patients with IBD are considered expensive to manage although their use of health care resources has not been sufficiently estimated. To date, few studies have quantified the total cost of caring for IBD patients, preferring to focus on the cost-effectiveness of specific treatments instead. Estimating the resources used and costs incurred when caring for IBD patients is crucial to help healthcare providers plan patient clinical management. This need intensifies with advances in biological therapies and genetic diagnostic tools such as microarrays. Our study developed a framework to estimate the total cost of caring for IBD patients. This framework allows both the estimation of the costs of current care pathways in various settings, and the economic analysis of proposed future interventions. We apply the framework to consider the cost of care for UC and CD patients in the UK and mainland Europe. Methods Decision models were built to simulate the natural disease history of UC and CD based on clinical pathways mapped in four European hospitals. A healthcare provider perspective was adopted and model inputs applied from published sources and expert opinion. Two hypothetical cohorts of 10 000 UC/CD patients presenting with symptoms of varying severity were modelled over a 10-year period. The average starting age ranged from 25 to 85 years and the models were adjusted to capture differences in clinical management across Europe. Healthcare cost data (test, treatment, surgery, consultation costs) were taken from UK sources and expressed in 2008 prices. Results The average cost of care over the entire 10-year period for a 45-year-old UC/CD patient was £8035/£7759 in the UK and £7657/£9546 in mainland Europe. These costs are comparable with previous estimates. The average cost per patient fell with patient age. Much of the clinical course for both patient groups was spent in remission, and most costs were incurred soon after diagnosis. The costs of surgery, azathioprine and hospital admission had the greatest effect on the results. Conclusion Our study confirms that IBD patients are expensive to manage and illustrates the importance of differentiating between alternative clinical management scenarios. The framework we develop is an informative analytical tool which allows healthcare providers to predict the resources required and costs incurred from treating both current and future IBD patients. We acknowledge EC financial support and assistance received from members of the IBDchip consortium.

W1018 Relationship Between the Location of Colonic Diverticulosis and the Visceral Fat Accumulation. Crucial Role of the Visceral Fat Accumulation for the Formation of Left Sided Colonic Diverticulosis

Introduction Inflammatory bowel disease (IBD) is a chronic condition affecting relatively young patients. It is unclear how these patients search for information on their disease. The goal of this survey was therefore to consider patient input in order to develop a specific website by identifying relevant target information more precisely. Methods The Swiss Inflammatory Bowel Disease Cohort (SIBDC) started in Nov. 2006 and has enrolled nearly 1600 patients in university centers, regional hospitals and private practices. Two short questionnaires were sent to all the patients in the cohort. The first, a short one-page questionnaire, was used to identify current information resources used by patients to gather information about disease. The second was a narrative questionnaire, used to identify which kind of specific information patients were seeking. The questionnaire was divided into 4 parts, each focusing on a different phase of disease history: 1st symptoms, time of diagnosis, worsening of disease and disease remission. Results Questionnaires were sent to the 1566 IBD patients enrolled in the cohort from Nov. 2006 to Sep. 2009. 64 were excluded (wrong address). 681 patients (45%) replied. The characteristics of those who responded were quite similar to the whole cohort. Information sources consulted to gather information on their disease were: gastroenterologist (90%), internet (67%), family doctor (38%), books (30%), TV (17%) and patient associations (13%). 586 (86%) patients accessed the internet at home or at work, 60% having access on a daily basis. The information currently sought by patients on websites was advances in research (37%), therapies (especially adverse effects of therapy and alternative medicine) (25%) and daily disease management tips (15%). Patients sought information at the time of their initial symptoms, mainly through physicians or the internet; 48% were satisfied with what they found. 80% of patients sought information just after initial diagnosis, 74% during flares or complications and 65% in periods of remission. The main information topic consulted during relapses concerned therapies (41% of patients who are seeking information); during periods of disease remission it was mostly linked to advances in research (44%). Conclusion This survey performed in a large national IBD cohort reports for the first time on how patients look for information on their chronic disease. Gastroenterologists and the internet are the main sources of information. These results will facilitate the creation of an information website tailored to patients' needs.

Impact of Race and Ethnicity on Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is now increasingly recognized in diverse ethnic populations. In the United States, IBD among the minority populations, especially Mexican Americans, has not been extensively studied. Apart from the known genetic influences that differ among the IBD subtypes [ulcerative colitis (UC) vs. Crohn's disease (CD)], serologic markers may differentiate UC and CD, including perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) in UC and CD. One hundred forty-eight patients with IBD seen in a university gastroenterology practice in Houston, Texas, between June 1999 and November 2003 were analyzed to determine whether there were significant differences among racial/ethnic groups. Whites comprised 40%, African Americans 37%, Mexican Americans 20%, and Asians 3% of the total IBD patients. We found that African Americans and whites predominantly had CD, whereas Mexican Americans predominantly had UC. There was no difference between African Americans and Mexican Americans when separately compared to whites in terms of intestinal manifestations of CD and UC, respectively. However, African Americans with CD had a significantly higher incidence of IBD-associated arthritis (p= 0.004) and ophthalmological manifestations, notably uveitis (p= 0.028), compared to whites with CD. Among UC patients, in comparison to the Mexican Americans, whites had significantly higher incidences of joint symptoms (p < 0.0001) and osteoporosis (p= 0.001). Whites had a stronger family history of IBD and colorectal carcinoma compared to the other ethnic groups. p-ANCA served as a sensitive marker for UC among Mexican Americans. All the Mexican Americans with UC tested had positive p-ANCA compared to only 40% of whites (p= 0.033). There are significant differences in IBD subtypes and serologic markers among racial/ ethnic groups with IBD in the United States.

Is a Diagnosis of Inflammatory Bowel Disease: Still a Contraindication for External Beam Radiotherapy in Prostate Cancer? - A Case Study Approach.

Introduction Inflammatory bowel disease (IBD) is generally considered a contraindication to irradiation in the pelvis. This case study hypothesises that a diagnosis of IBD no longer precludes the delivery of high doses to treat prostate cancer when using conformal radiotherapy techniques. Methods The case histories of 2 IBD patients who had recently received dose-escalated radiotherapy for prostate cancer were reviewed. A DVH ranking comparison was made for the rectal wall of these patients using 4 prostate treatment plans to examine each technique's contribution to rectal dose. Results The actual treatment plan delivered the dose prescribed (75.6Gy) without any toxicity to date. This plan reduced the maximum dose whilst minimizing the rectum contained within the 40Gy and 60Gy volumes. Discussion Avoidance of radiation therapy, secondary to toxicity concerns, may jeopardize the clinical outcome for IBD patients. The results from this case study support the hypothesis that precision techniques may be employed to safely treat IBD patients to a tumoricidal dose but an investigation with larger patient numbers is warranted to reach any fi rm conclusions regarding the safe management of these patients.