The latest research findings and advances in the treatment of inflammatory bowel disease (IBD) were recently presented at the British Society of Gastroenterologists’ annual conference. Among the research highlighted at the event included an analysis of the National IBD Audit, involving 2,981 patients, which offered an insight into the outcome of acute severe ulcerative colitis. Researchers from the Clinical Evaluation and Effectiveness Unit of the Royal College of Physicians found that inpatient mortality was 1.2% with death being strongly associated with increased age, male sex and Clostridium difficile infection. Importantly, analysis of the data showed that, if first line medical treatment fails, the risk of death further increases to 2.8%. Over 60% of patients responded to first line treatment with steroids. In addition, of the 317 who failed treatment with steroids, 108 underwent surgery without further medical treatment, 98 were treated with cyclosporine and 52 with infliximab. Significantly, the response rate to infliximab was higher than to cyclosporine (75% vs 46%). Overall, 163 underwent surgery with a median time to surgery of 10 days. The researchers found that post-operative mortality did not differ between those patients coming to surgery before and after seven days following admission. They concluded that effective communication between medical and surgical teams, clear decision making and timely surgery will be required to keep mortality to a minimum.1 The results of the latest studies investigating possible treatments for gastrointestinal diseases were also presented. Scientists at the University of Nottingham investigated whether the hookworm, Necator Americanus, could help to reduce symptoms of Crohn’s, for example.
In regions where hookworm is prevalent – such as sub-Saharan Africa and south-east Asia – inflammatory bowel diseases (IBD) such as Crohn’s and ulcerative colitis are extremely rare. One theory put forward is that the worms help to “down-regulate” the human immune system, to stop it reacting in a way that causes the symptoms of diseases like Crohn’s. It is thought that the parasites have evolved a way of surviving in the gut by “turning down” the immune response so the body does not attack them. Patients were infected with hookworms for a 12-week period as part of the study – conducted by Dr Paul Fortun and Professor Chris Hawkey of the University’s Wolfson Digestive Diseases Centre, and Professor David Pritchard, an immunoparasitologist in the School of Pharmacy. The research findings appeared to exclude any significant benefit. However, further analysis will be needed to determine whether apparent deteriorations in the Crohn’s disease activity index may reflect gastrointestinal symptoms induced by hookworm infection and whether there may be a benefit in subgroups. Further work could explore whether different dosing regimens would be more successful. New light was also shed on the use of prebiotics in the treatment of active Crohn’s disease, at the conference. A randomised, double-blind, placebocontrolled trial has suggested that patients who received a diet supplemented with prebiotics (fructo-oligosaccarides) showed no clinical benefit despite impacting on dendritic cell immunity.2 On a positive note, a study carried out on patients in Norwich, investigating dietary intake of oleic acid, found that this may help to prevent ulcerative colitis.3 There has also been advances in the area of diagnostics. Earlier this year, researchers announced that testing had begun on a device that could “sniff out” the presence of diseases of the gut. OdoReader, developed by Chris Probert from the University of Bristol and Norman Ratcliffe from the University of the West of England, was designed to rapidly diagnose C. difficile, by “reading” the odour of stool samples. With the help of University Hospitals Bristol NHS Foundation Trust, the technology enables gasses emitted from faeces to be analysed in under an hour, leading to a rapid and inexpensive diagnosis.
Chris Probert, professor of Gastroenterology at the University of Bristol, and consultant gastroenterologist at University Hospitals Bristol, said: “For a long time it has been known that stools have a distinctive and different odour if there is an infection. What the device does is take this ‘knowledge’ a step further by comparing the odour of faeces of patients with those from patients with specific gastro-intestinal disease to make a rapid diagnosis at point of care.” Supported by an award of £1.3 million from the Wellcome Trust, the device will be tested against the industry “gold standard” method of diagnosis and the final product will undergo a clinical trial before becoming available for commercialisation in 2012/13.4 More recently, the potential of “scenting” was further investigated by Chris Probert and colleagues at the University of Bristol to differentiate between irritable bowel syndrome and inflammatory bowel disease. The research team (including Iftikhar Ahmed, Rosemary Greenwood and Chris Probert) explained that IBS is considered to be a functional disorder of the gastrointestinal tract, the cause of which remains inadequately identified. Since there are no diagnostic markers, symptoms-based criteria are currently used to confirm the diagnosis. Due to similar presentation, however, it is difficult to distinguish IBS from IBD in both primary care and specialist settings. A cohort of 90 individuals were studied and faecal samples analysed by gas chromatography/mass spectrometry. Some 90% of patients were correctly diagnosed and the model proved to have a sensitivity of 95%. The team concluded that the interim results show that volatile organic compounds may be used to distinguish IBS from IBD and both from healthy controls.
Future of IBD care
Dr Orchard highlighted the increasing personalisation of care for patients with IBD. Genetics are an extremely important area, he explained, and the development of chip-based technology has allowed researchers to analyse a vast number of polymorphisms. “There are now over 30 areas of the genome identified as being associated with Crohn’s disease, and many of these are concerned with how the body interacts and deals with luminal bacteria in the gut – pointing strongly towards the direction in which we need to go,” he commented. “The role of microbiota will come under increasing scrutiny.” In the future, there will be three key areas of focus – new treatments, new methods of targeting treatments and new models of delivering care to patients. “In particular, it would be helpful if we were able to identify who will respond in advance of administering a treatment and who may be at risk of complications, so that we can intervene at an early stage,” he commented. “It may be possible, in the future, to genetically test patients to predict outcome – effectively developing a ‘prognosis chip’ or ‘treatment response chip’. The goal is to link genetic, immunological and microbiotic analysis to predict the disease course.” In view of the financial constraints on the NHS, self-management of long-term conditions will become increasingly important and IBD nurses will have a significant role in delivering this model of care, he pointed out. Improved relationships between primary and secondary care need to be negotiated to ensure patients receive good, high quality treatment in the place that is most appropriate. “The key to this is the use of appropriate information technology. We need an IBD database that is useable in real-time. Work is underway to create an IBD register. However, this should be accessible for both primary and secondary care, to ensure that all those involved with a patient’s care have access to the information they need. It should also enable the recall of patients to allow ongoing monitoring of their condition,” he concluded. “We need to ensure that the IBD standards are properly implemented and that there are better levels of recruitment of patients into clinical trials. Ultimately, as a community of doctors, scientists and patients, we need to be working together to take forward our understanding of IBD.”
References
1 Arnott I.D.R., Leiper K., Lowe D., Potter J., Rhodes J.M. Clinical Evaluation and Effectiveness Unit, the Royal College of Physicians. 2 Benjamin J.L., Hedin., C.R. H., Koutsoumpas A., Sanderson J.D., King’s College London; Ng, S.C., Hart A.L., Knight S.C., Imperial College London; Forbes A., University College London; Stagg A.J., Blizard Institute of Cell and Molecular Science, London; Lindsay J.O., Barts and the London School of Medicine. 3 de Silva P.S.A., Norfolk and Norwich University Hospital; Luben R., University of Cambridge; Welch A., University of East Anglia; Khaw K., Addenbrooke’s Hospital; Hart A.R., University of East Anglia. 4 Press release issued by University of Bristol, accessed at: www.bris.ac.uk/ news/2010/6824.html 5 Hunter J., James S., Chan D., Stacey B., Stroud M., Patel P., Cummings F., Fine D. Southampton General Hospital.