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Title: Diagnostic potential of volatile organic compounds as faecal biomarkers in inflammatory bowel disease
Author: Ahmed, Iftikhar
ISNI:       0000 0004 2724 6588
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Introduction: Inflammatory bowel disease (IBD) is a chronic, remitting and relapsing disease of the gastrointestinal tract, the aetiology of which remains elusive. Diagnosis of IBD requires complex and invasive procedures. Endoscopy and histology of biopsy specimens remain the current "gold standard" for detecting and quantifying bowel inflammation. Due to similarity of symptoms of IBD and irritable bowel syndrome (IBS), invasive procedures are used excessively to differentiate the two conditions which have significant safety and economical implications. Currently available non-invasive serological markers (such as CRP and ESR) are unreliable due to their poor correlation with clinical and endoscopic findings. Volatile organic compounds (VOCs) are chemicals, which may be emitted from faeces, and other bodily fluids, and are responsible for their characteristic odours. Historically, changes in the smell of human excreta may be assigned to various illnesses; so understanding these changes in the smell by identifying its volatile signature can be of diagnostic value. Objective: To evaluate the faecal VOCs in the diagnosis of IBD and compare them with those from the patients with I BS and healthy controls Method: We studied samples from 356 individuals, 30 with diarrhoea predominant IBS, 217 with IBD (Crohn's disease=117, ulcerative colitis=100), and 109 healthy individuals. Faecal volatile were extracted using SPME (solid phase micro-extraction) technique and were analysed by GC-MS (gas chromatography-mass spectrometery). VOCs were identified using the NIST (National Institute of Science and Technology) library and manual visualization using the fragmentation pattern when appropriate. Results: From the 350 VOCs identified in these experiments, univariate analysis was used to identify those VOCs, which were statistically significant (p< 0.05) in discriminating between the groups. A forward stepwise discriminant function analysis was used to develop a predictive model, which showed significant value in separating active IBD cases from those with disease in remission, IBS and healthy controls (p<0.05). The model was able to differentiate active CD from inactive CD and from healthy controls. Similarly the model was able to differentiate active UC from inactive UC and healthy controls. The model also showed statistically significant value in discriminating IBS from active IBD and healthy controls. On cross-validation, the model remained stable: 90% of patients were correctly diagnosed. This model has overall sensitivity of 90% and specificity 80%. Conclusion: These results show that VOCs analysis has the potential to provide a non- invasive means of diagnosing IBD, monitoring the disease activity and to differentiate it from IBS. This technique is fast and convenient and opens up a promising area for use as a non- invasive diagnostic tool with advantages of providing a much-needed, reliable, real-time and point of care diagnosis and monitoring of various gastrointestinal disorders.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available