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Ramesh P. Arasaradnam - One of the best experts on this subject based on the ideXlab platform.
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Non-invasive exhaled volatile organic biomarker analysis to detect inflammatory bowel disease (IBD)
Digestive and Liver Disease, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Jim R. Skinner, Nicola O'connell, Subiatu Wurie, Samantha Chambers, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. SavageAbstract:Abstract IntroductIon Early inflammatory bowel disease (IBD) diagnosis remains a clinical challenge. Volatile organic compounds (VOCs) have shown distinct patterns in Crohn's disease (CD) and ulcerative colitis (UC). VOC productIon, reflecting gut fermentome metabolites, is perturbed in IBD. VOC sampling is non-invasive, with various compounds identified from faecal, breath and urine samples. This study aimed to determine if FAIMS (field asymmetric Ion Mobility Spectroscopy) analysis of exhaled VOCs could distinguish IBD from controls. Methods Seventy-six subjects were recruited, 54 established IBD (25 CD, 29 UC) and 22 healthy controls. End expiratory breath was captured using a Warwick device and analysed by FAIMS. Data were pre-processed using wavelet transformatIon, and classificatIon performed in a 10-fold cross-validatIon. Feature selectIon was performed using Wilcoxon rank sum test, and sparse logistic regressIon gave class predictIons, to calculate sensitivity and specificity. Results FAIMS breath VOC analysis showed clear separatIon of IBD from controls, sensitivity: 0.74 (0.65–0.82), specificity: 0.75 (0.53–0.90), AUROC: 0.82 (0.74–0.89), p -value 6.2 × 10 −7 . IBD subgroup analysis distinguished UC from CD: sensitivity of 0.67 (0.54–0.79), specificity: 0.67 (0.54–0.79), AUROC: 0.70 (0.60–0.80), p -value 9.23 × 10 −4 . ConclusIon This confirms the utility of exhaled VOC analysis to distinguish IBD from healthy controls, and UC from CD. It conforms to other studies using different technology, whilst affirming exhaled VOCs as biomarkers for diagnosing IBD.
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PWE-136 The non-invasive detectIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: a pilot study
Gut, 2015Co-Authors: James A. Covington, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, E. Westenbrink, Ramesh P. ArasaradnamAbstract:IntroductIon Non Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods, including that of the Fibroscan, have limitatIons, thus there is a clinical need for more robust, non-invasive screening tools. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns. These patterns are detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We aimed to determine if progressive fatty liver disease produced an altered VOC pattern in urine; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). Method 34 patients were recruited; 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40 ± 0.1°C and the headspace analysed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a ‘Random Forrest’ classificatIon algorithm and a 10 fold cross validatIon method was applied. Results Urinary VOCs could distinguish liver disease patients from controls with a sensitivity of 0.58 (0.33–0.88) but specificity of 0.93 (0.68 – 1.00); Area Under Curve (AUC) 0.73 (0.55 – 0.90). NASH/NASH-C was similarly separated from the NAFLD/control patients with a sensitivity of 0.73 (0.45–0.92), a specificity of 0.79 (0.54–0.94) and AUC of 0.79 (0.64–0.95), respectively. ConclusIon This pilot study offers the potential for early non-invasive tracking of liver disease using urinary VOC bio-odorant fingerprints to distinguish patients with a disease within the spectrum of fatty liver disease from healthy controls, but also to distinguish subsets of the spectrum from each other, such as NASH from NAFLD. This may develop into a viable alternative surveillance or diagnostic tool in patients unable or unwilling to undergo liver biopsy. Disclosure of interest None Declared.
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Non-invasive distinctIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: early results.
Journal of gastrointestinal and liver diseases : JGLD, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, Eric W. Westenbrink, James A. CovingtonAbstract:BACKGROUND & AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitatIons, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). METHODS: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classificatIon algorithm and using a 10 fold cross validatIon method was applied. RESULTS: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 - 0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively. CONCLUSIonS: This pilot study suggests that urinary VOCs detectIon may offer the potential for early non-invasive characterisatIon of liver disease using 'smell prints' to distinguish between NASH and NAFLD.
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DetectIon of colorectal cancer (CRC) by urinary volatile organic compound analysis.
PloS one, 2014Co-Authors: Ramesh P. Arasaradnam, Michael Mcfarlane, Nicola O'connell, Samantha Chambers, Eric W. Westenbrink, Catherine Bailey, Matthew G. Thomas, Courtenay Ryan-fisher, Paula Hodges, Christopher HarmstonAbstract:Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of populatIon based FOBt testing in the UK is also low at around 50%. The detectIon of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extractIon from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detectIon with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using Ion Mobility Spectroscopy technology (FAIMS) with potential as a novel screening tool.
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Review article: next generatIon diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detectIon
Alimentary pharmacology & therapeutics, 2014Co-Authors: Ramesh P. Arasaradnam, James A. Covington, Christopher Harmston, Chuka U. NwokoloAbstract:Background The detectIon of airborne gas phase biomarkers that emanate from biological samples like urine, breath and faeces may herald a new age of non-invasive diagnostics. These biomarkers may reflect status in health and disease and can be detected by humans and other animals, to some extent, but far more consistently with instruments. The continued advancement in micro and nanotechnology has produced a range of compact and sophisticated gas analysis sensors and sensor systems, focussed primarily towards environmental and security applicatIons. These instruments are now increasingly adapted for use in clinical testing and with the discovery of new gas volatile compound biomarkers, lead naturally to a new era of non-invasive diagnostics. Aim To review current sensor instruments like the electronic nose (e-nose) and Ion Mobility Spectroscopy (IMS), existing technology like gas chromatography-mass Spectroscopy (GC-MS) and their applicatIon in the detectIon of gas phase volatile compound biomarkers in medicine – focussing on gastroenterology. Methods A systematic search on Medline and Pubmed databases was performed to identify articles relevant to gas and volatile organic compounds. Results E-nose and IMS instruments achieve sensitivities and specificities ranging from 75 to 92% in differentiating between inflammatory bowel disease, bile acid diarrhoea and colon cancer from controls. For pulmonary disease, the sensitivities and specificities exceed 90% in differentiating between pulmonary malignancy, pneumonia and obstructive airways disease. These sensitivity levels also hold true for diabetes (92%) and bladder cancer (90%) when GC-MS is combined with an e-nose. ConclusIons The accurate reproducible sensing of volatile organic compounds (VOCs) using portable near-patient devices is a goal within reach for today's clinicians.
David E. Clemmer - One of the best experts on this subject based on the ideXlab platform.
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Direct Measurement of the IsomerizatIon Barrier of the Isolated Retinal Chromophore
Journal of Physics: Conference Series, 2015Co-Authors: Jonathan M. Dilger, Lihi Musbat, Mordechai Sheves, Anastasia V. Bochenkova, David E. Clemmer, Yoni TokerAbstract:Energy barrier Heights for isomerizatIon of the isolated retinal chromophore were measured using two stages of Ion Mobility Spectroscopy (IMS-IMS).
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developing liquid chromatography Ion Mobility mass spectometry techniques
Expert Review of Proteomics, 2005Co-Authors: Stephen J Valentine, Manolo D Plasencia, Amy E Hilderbrand, Ruwan T Kurulugama, Stormy L Koeniger, David E. ClemmerAbstract:When a packet of Ions in a buffer gas is exposed to a weak electric field, the Ions will separate according to differences in their mobilities through the gas. This separatIon forms the basis of the analytical method known as Ion Mobility Spectroscopy and is highly efficient, in that it can be carried out in a very short time frame (micro- to milliseconds). Recently, efforts have been made to couple the approach with liquid-phase separatIons and mass spectrometry in order to create a high-throughput and high-coverage approach for analyzing complex mixtures. This article reviews recent work to develop this approach for proteomics analyses. The instrumentatIon is described briefly. Several multidimensIonal data sets obtained upon analyzing complex mixtures are shown in order to illustrate the approach as well as provide a view of the limitatIons and required future work.
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EvaluatIon of Ion Mobility Spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers
Journal of the American Society for Mass Spectrometry, 2005Co-Authors: Richard L. Wong, Evan R. Williams, Anne E. Counterman, David E. ClemmerAbstract:The cross sectIons of five different protonated trimers consisting of two base molecules and trifluoroacetic acid were measured by using Ion Mobility spectrometry. The gas-phase basicities of these five base molecules span an 8-kcal/mol range. These cross sectIons are compared with those determined from candidate low-energy salt-bridge and charge-solvated structures identified by using molecular mechanics calculatIons using three different force fields: AMBER*, MMFF, and CHARMm. With AMBER*, the charge-solvated structures are all globular and the salt-bridge structures are all linear, whereas with CHARMm, these two forms of the protonated trimers can adopt either shape. Globular structures have smaller cross sectIons than linear structures. ConclusIons about the structure of these protonated trimers are highly dependent on the force field used to generate low-energy candidate structures. With AMBER*, all of the trimers are consistent with salt-bridge structures, whereas with MMFF the measured cross sectIons are more consistent with charge-solvated structures, although the assignments are ambiguous for two of the protonated trimers. ConclusIons based on structures generated by using CHARMm suggest a change in structure from charge-solvated to salt-bridge structures with increasing gas-phase basicity of the constituent bases, a result that is most consistent with structural conclusIons based on blackbody infrared radiative dissociatIon experiments for these protonated trimers and theoretical calculatIons on the uncharged base-acid pairs.
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Developing liquid chromatography Ion Mobility mass spectometry
2005Co-Authors: Xiaoyun Liu, Manolo D Plasencia, David E. ClemmerAbstract:When a packet of Ions in a buffer gas is exposed to a weak electric field, the Ions will separate according to differences in their mobilities through the gas. This separatIon forms the basis of the analytical method known as Ion Mobility Spectroscopy and is highly efficient, in that it can be carried out in a very short time frame (micro- to milliseconds). Recently, efforts have been made to couple the approach with liquid-phase separatIons and mass spectrometry in order to create a high-throughput and high-coverage approach for analyzing complex mixtures. This article reviews recent work to develop this approach for proteomics analyses. The instrumentatIon is described briefly. Several multidimensIonal data sets obtained upon analyzing complex mixtures are shown in order to illustrate the approach as well as provide a view of the limitatIons and required future work.
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FOCUS :N OVEL APPROACHES TO PEPTIDE AND PROTEIN STRUCTURE EvaluatIon of Ion Mobility Spectroscopy for Determining Charge-Solvated versus Salt-Bridge Structures of Protonated Trimers
2005Co-Authors: Richard L. Wong, Evan R. Williams, Anne E. Counterman, David E. ClemmerAbstract:The cross sectIons of five different protonated trimers consisting of two base molecules and trifluoroacetic acid were measured by using Ion Mobility spectrometry. The gas-phase basicities of these five base molecules span an 8-kcal/mol range. These cross sectIons are compared with those determined from candidate low-energy salt-bridge and charge-solvated structures identified by using molecular mechanics calculatIons using three different force fields: AMBER*, MMFF, and CHARMm. With AMBER*, the charge-solvated structures are all globular and the salt-bridge structures are all linear, whereas with CHARMm, these two forms of the protonated trimers can adopt either shape. Globular structures have smaller cross sectIons than linear structures. ConclusIons about the structure of these protonated trimers are highly dependent on the force field used to generate low-energy candidate structures. With AMBER*, all of the trimers are consistent with salt-bridge structures, whereas with MMFF the measured cross sectIons are more consistent with charge-solvated structures, although the assignments are ambiguous for two of the protonated trimers. ConclusIons based on structures generated by using CHARMm suggest a change in structure from charge-solvated to salt-bridge structures with increasing gas-phase basicity of the constituent bases, a result that is most consistent with structural conclusIons based on blackbody infrared radiative dissociatIon experiments for these protonated trimers and theoretical calculatIons on the uncharged base–acid pairs. (J Am Soc Mass Spectrom 2005, 16, 1009 –1019) © 2005 American Society for Mass Spectrometry
James A. Covington - One of the best experts on this subject based on the ideXlab platform.
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PWE-136 The non-invasive detectIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: a pilot study
Gut, 2015Co-Authors: James A. Covington, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, E. Westenbrink, Ramesh P. ArasaradnamAbstract:IntroductIon Non Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods, including that of the Fibroscan, have limitatIons, thus there is a clinical need for more robust, non-invasive screening tools. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns. These patterns are detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We aimed to determine if progressive fatty liver disease produced an altered VOC pattern in urine; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). Method 34 patients were recruited; 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40 ± 0.1°C and the headspace analysed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a ‘Random Forrest’ classificatIon algorithm and a 10 fold cross validatIon method was applied. Results Urinary VOCs could distinguish liver disease patients from controls with a sensitivity of 0.58 (0.33–0.88) but specificity of 0.93 (0.68 – 1.00); Area Under Curve (AUC) 0.73 (0.55 – 0.90). NASH/NASH-C was similarly separated from the NAFLD/control patients with a sensitivity of 0.73 (0.45–0.92), a specificity of 0.79 (0.54–0.94) and AUC of 0.79 (0.64–0.95), respectively. ConclusIon This pilot study offers the potential for early non-invasive tracking of liver disease using urinary VOC bio-odorant fingerprints to distinguish patients with a disease within the spectrum of fatty liver disease from healthy controls, but also to distinguish subsets of the spectrum from each other, such as NASH from NAFLD. This may develop into a viable alternative surveillance or diagnostic tool in patients unable or unwilling to undergo liver biopsy. Disclosure of interest None Declared.
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Non-invasive distinctIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: early results.
Journal of gastrointestinal and liver diseases : JGLD, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, Eric W. Westenbrink, James A. CovingtonAbstract:BACKGROUND & AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitatIons, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). METHODS: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classificatIon algorithm and using a 10 fold cross validatIon method was applied. RESULTS: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 - 0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively. CONCLUSIonS: This pilot study suggests that urinary VOCs detectIon may offer the potential for early non-invasive characterisatIon of liver disease using 'smell prints' to distinguish between NASH and NAFLD.
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Review article: next generatIon diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detectIon
Alimentary pharmacology & therapeutics, 2014Co-Authors: Ramesh P. Arasaradnam, James A. Covington, Christopher Harmston, Chuka U. NwokoloAbstract:Background The detectIon of airborne gas phase biomarkers that emanate from biological samples like urine, breath and faeces may herald a new age of non-invasive diagnostics. These biomarkers may reflect status in health and disease and can be detected by humans and other animals, to some extent, but far more consistently with instruments. The continued advancement in micro and nanotechnology has produced a range of compact and sophisticated gas analysis sensors and sensor systems, focussed primarily towards environmental and security applicatIons. These instruments are now increasingly adapted for use in clinical testing and with the discovery of new gas volatile compound biomarkers, lead naturally to a new era of non-invasive diagnostics. Aim To review current sensor instruments like the electronic nose (e-nose) and Ion Mobility Spectroscopy (IMS), existing technology like gas chromatography-mass Spectroscopy (GC-MS) and their applicatIon in the detectIon of gas phase volatile compound biomarkers in medicine – focussing on gastroenterology. Methods A systematic search on Medline and Pubmed databases was performed to identify articles relevant to gas and volatile organic compounds. Results E-nose and IMS instruments achieve sensitivities and specificities ranging from 75 to 92% in differentiating between inflammatory bowel disease, bile acid diarrhoea and colon cancer from controls. For pulmonary disease, the sensitivities and specificities exceed 90% in differentiating between pulmonary malignancy, pneumonia and obstructive airways disease. These sensitivity levels also hold true for diabetes (92%) and bladder cancer (90%) when GC-MS is combined with an e-nose. ConclusIons The accurate reproducible sensing of volatile organic compounds (VOCs) using portable near-patient devices is a goal within reach for today's clinicians.
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PTH-187 A Novel Non-Invasive Approach to Diagnose Bile Acid Diarrhoea (Bad) using an Electronic Nose (E-Nose) and Field Asymmetric Ion Mobility Spectroscopy (Faims)
Gut, 2013Co-Authors: James A. Covington, Nicola O'connell, Chuka U. Nwokolo, Karna Dev Bardhan, Catherine Bailey, E Westinbrink, Matthew G. Thomas, J Cullis, Nigel Williams, Ramesh P. ArasaradnamAbstract:IntroductIon A third of diarrhoea predominant irritable bowel syndrome (D-IBS) results from bile acid malabsorptIon (BAM); diagnosed by 75 SeHCAT retentIon test. We have previously demonstrated the ability of using an E-nose and FAIMS to detect inflammatory bowel disease (IBD) by shifts in the patterns of volatile organic compounds (VOCs) in the gases and vapours that emanate from urine samples. Here, we have extended our work to detect BAM from urine odours alone. Methods Technology Principles - E-nose This uses an array of gas phase chemical sensors which are broadly tuned to different chemical groups. When a urine sample is presented to the sensor array, a unique response is produced. By taking all of the sensor responses together, a bio-odorant fingerprint is created. FAIMS operates on similar principles, but produces its fingerprint by measuring the differences in Mobility of Ionised chemicals in high electric fields. Subjects and patients BAM (7 day retentIon value of o C. The headspace (the air above the sample) was then pumped from the containers and analysed by an AlphaMOS FOX 4000 E-nose and FAIMS instrument. Discriminant FunctIon Analysis and Fisher Discriminant Analysis (FDA) were used for statistical evaluatIon, respectively. Results The FOX 4000 E-nose plot (Figure 1) shows separate and distinct groupings of patients with BAM, UC, and healthy controls. FAIMS analysis gave a broadly similar pattern (not shown). ConclusIon D-IBS related to BAM is a common conditIon and treatment with BA sequestrants is effective in the majority. The SeHCAT retentIon test makes diagnosis easy but is not available in all centres: our pilot data offers an alternative diagnostic approach with high potential. Disclosure of Interest None Declared.
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Mo1394 Towards the DetectIon of Bile Acid Diarrhea: A Novel Non-Invasive Approach Using Electronic Noses (E-Nose) and Field Asymmetric Ion Mobility Spectroscopy (FAIMS)
Gastroenterology, 2013Co-Authors: James A. Covington, Nicola O'connell, Chuka U. Nwokolo, Karna Dev Bardhan, Eric W. Westenbrink, Mathew Thomas, Catherine Bailey, Ramesh P. ArasaradnamAbstract:OBJECTIVES: Colorectal cancer develops through multiple pathways including the adenomacarcinoma sequence and the serrated pathway. Individuals with serrated polyps (SP) are at higher risk of developing synchronous advanced colorectal neoplasia (AN) and cancer, but the molecular pathways underlying this malignancy remain poorly understood in these individuals. In this study, we characterized patients with coexisting colorectal AN and SP by examining the methylatIon levels of long interspersed nucleotide element-1 (LINE-1) in the adjacent normal mucosal tissues. METHODS: Colorectal ANs were retrospectively collected. The case group included ANs with coexisting SPs, and the control group consisted of ANs without coexisting SPs. Clinicopathological findings were compared between groups. BRAF and KRAS mutatIons in the ANs and SPs and LINE-1 methylatIon levels in adjacent mucosa were examined by quantitative bisulfite pyrosequencing. RESULTS: Seventy-five ANs from 40 patients in the case group, and 179 ANs from 119 patients in the control group were collected and analyzed. There were no significant differences in clinicopathological findings between the 2 groups of ANs, except that intraepithelial neoplasia in the case group was more frequently located in the right colon. BRAF mutatIons were significantly more frequent in the case group, while KRAS mutatIon showed no significant differences between groups. Most patients with high-grade intraepithelial neoplasia in both groups showed a component of conventIonal adenoma, while only one patient with high-grade intraepithelial neoplasia in the control group had a component of SP. Individuals with
Chuka U. Nwokolo - One of the best experts on this subject based on the ideXlab platform.
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Non-invasive exhaled volatile organic biomarker analysis to detect inflammatory bowel disease (IBD)
Digestive and Liver Disease, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Jim R. Skinner, Nicola O'connell, Subiatu Wurie, Samantha Chambers, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. SavageAbstract:Abstract IntroductIon Early inflammatory bowel disease (IBD) diagnosis remains a clinical challenge. Volatile organic compounds (VOCs) have shown distinct patterns in Crohn's disease (CD) and ulcerative colitis (UC). VOC productIon, reflecting gut fermentome metabolites, is perturbed in IBD. VOC sampling is non-invasive, with various compounds identified from faecal, breath and urine samples. This study aimed to determine if FAIMS (field asymmetric Ion Mobility Spectroscopy) analysis of exhaled VOCs could distinguish IBD from controls. Methods Seventy-six subjects were recruited, 54 established IBD (25 CD, 29 UC) and 22 healthy controls. End expiratory breath was captured using a Warwick device and analysed by FAIMS. Data were pre-processed using wavelet transformatIon, and classificatIon performed in a 10-fold cross-validatIon. Feature selectIon was performed using Wilcoxon rank sum test, and sparse logistic regressIon gave class predictIons, to calculate sensitivity and specificity. Results FAIMS breath VOC analysis showed clear separatIon of IBD from controls, sensitivity: 0.74 (0.65–0.82), specificity: 0.75 (0.53–0.90), AUROC: 0.82 (0.74–0.89), p -value 6.2 × 10 −7 . IBD subgroup analysis distinguished UC from CD: sensitivity of 0.67 (0.54–0.79), specificity: 0.67 (0.54–0.79), AUROC: 0.70 (0.60–0.80), p -value 9.23 × 10 −4 . ConclusIon This confirms the utility of exhaled VOC analysis to distinguish IBD from healthy controls, and UC from CD. It conforms to other studies using different technology, whilst affirming exhaled VOCs as biomarkers for diagnosing IBD.
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PWE-136 The non-invasive detectIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: a pilot study
Gut, 2015Co-Authors: James A. Covington, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, E. Westenbrink, Ramesh P. ArasaradnamAbstract:IntroductIon Non Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods, including that of the Fibroscan, have limitatIons, thus there is a clinical need for more robust, non-invasive screening tools. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns. These patterns are detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We aimed to determine if progressive fatty liver disease produced an altered VOC pattern in urine; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). Method 34 patients were recruited; 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40 ± 0.1°C and the headspace analysed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a ‘Random Forrest’ classificatIon algorithm and a 10 fold cross validatIon method was applied. Results Urinary VOCs could distinguish liver disease patients from controls with a sensitivity of 0.58 (0.33–0.88) but specificity of 0.93 (0.68 – 1.00); Area Under Curve (AUC) 0.73 (0.55 – 0.90). NASH/NASH-C was similarly separated from the NAFLD/control patients with a sensitivity of 0.73 (0.45–0.92), a specificity of 0.79 (0.54–0.94) and AUC of 0.79 (0.64–0.95), respectively. ConclusIon This pilot study offers the potential for early non-invasive tracking of liver disease using urinary VOC bio-odorant fingerprints to distinguish patients with a disease within the spectrum of fatty liver disease from healthy controls, but also to distinguish subsets of the spectrum from each other, such as NASH from NAFLD. This may develop into a viable alternative surveillance or diagnostic tool in patients unable or unwilling to undergo liver biopsy. Disclosure of interest None Declared.
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Non-invasive distinctIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: early results.
Journal of gastrointestinal and liver diseases : JGLD, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, Eric W. Westenbrink, James A. CovingtonAbstract:BACKGROUND & AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitatIons, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). METHODS: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classificatIon algorithm and using a 10 fold cross validatIon method was applied. RESULTS: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 - 0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively. CONCLUSIonS: This pilot study suggests that urinary VOCs detectIon may offer the potential for early non-invasive characterisatIon of liver disease using 'smell prints' to distinguish between NASH and NAFLD.
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Review article: next generatIon diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detectIon
Alimentary pharmacology & therapeutics, 2014Co-Authors: Ramesh P. Arasaradnam, James A. Covington, Christopher Harmston, Chuka U. NwokoloAbstract:Background The detectIon of airborne gas phase biomarkers that emanate from biological samples like urine, breath and faeces may herald a new age of non-invasive diagnostics. These biomarkers may reflect status in health and disease and can be detected by humans and other animals, to some extent, but far more consistently with instruments. The continued advancement in micro and nanotechnology has produced a range of compact and sophisticated gas analysis sensors and sensor systems, focussed primarily towards environmental and security applicatIons. These instruments are now increasingly adapted for use in clinical testing and with the discovery of new gas volatile compound biomarkers, lead naturally to a new era of non-invasive diagnostics. Aim To review current sensor instruments like the electronic nose (e-nose) and Ion Mobility Spectroscopy (IMS), existing technology like gas chromatography-mass Spectroscopy (GC-MS) and their applicatIon in the detectIon of gas phase volatile compound biomarkers in medicine – focussing on gastroenterology. Methods A systematic search on Medline and Pubmed databases was performed to identify articles relevant to gas and volatile organic compounds. Results E-nose and IMS instruments achieve sensitivities and specificities ranging from 75 to 92% in differentiating between inflammatory bowel disease, bile acid diarrhoea and colon cancer from controls. For pulmonary disease, the sensitivities and specificities exceed 90% in differentiating between pulmonary malignancy, pneumonia and obstructive airways disease. These sensitivity levels also hold true for diabetes (92%) and bladder cancer (90%) when GC-MS is combined with an e-nose. ConclusIons The accurate reproducible sensing of volatile organic compounds (VOCs) using portable near-patient devices is a goal within reach for today's clinicians.
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PTH-187 A Novel Non-Invasive Approach to Diagnose Bile Acid Diarrhoea (Bad) using an Electronic Nose (E-Nose) and Field Asymmetric Ion Mobility Spectroscopy (Faims)
Gut, 2013Co-Authors: James A. Covington, Nicola O'connell, Chuka U. Nwokolo, Karna Dev Bardhan, Catherine Bailey, E Westinbrink, Matthew G. Thomas, J Cullis, Nigel Williams, Ramesh P. ArasaradnamAbstract:IntroductIon A third of diarrhoea predominant irritable bowel syndrome (D-IBS) results from bile acid malabsorptIon (BAM); diagnosed by 75 SeHCAT retentIon test. We have previously demonstrated the ability of using an E-nose and FAIMS to detect inflammatory bowel disease (IBD) by shifts in the patterns of volatile organic compounds (VOCs) in the gases and vapours that emanate from urine samples. Here, we have extended our work to detect BAM from urine odours alone. Methods Technology Principles - E-nose This uses an array of gas phase chemical sensors which are broadly tuned to different chemical groups. When a urine sample is presented to the sensor array, a unique response is produced. By taking all of the sensor responses together, a bio-odorant fingerprint is created. FAIMS operates on similar principles, but produces its fingerprint by measuring the differences in Mobility of Ionised chemicals in high electric fields. Subjects and patients BAM (7 day retentIon value of o C. The headspace (the air above the sample) was then pumped from the containers and analysed by an AlphaMOS FOX 4000 E-nose and FAIMS instrument. Discriminant FunctIon Analysis and Fisher Discriminant Analysis (FDA) were used for statistical evaluatIon, respectively. Results The FOX 4000 E-nose plot (Figure 1) shows separate and distinct groupings of patients with BAM, UC, and healthy controls. FAIMS analysis gave a broadly similar pattern (not shown). ConclusIon D-IBS related to BAM is a common conditIon and treatment with BA sequestrants is effective in the majority. The SeHCAT retentIon test makes diagnosis easy but is not available in all centres: our pilot data offers an alternative diagnostic approach with high potential. Disclosure of Interest None Declared.
Nicola O'connell - One of the best experts on this subject based on the ideXlab platform.
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Non-invasive exhaled volatile organic biomarker analysis to detect inflammatory bowel disease (IBD)
Digestive and Liver Disease, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Jim R. Skinner, Nicola O'connell, Subiatu Wurie, Samantha Chambers, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. SavageAbstract:Abstract IntroductIon Early inflammatory bowel disease (IBD) diagnosis remains a clinical challenge. Volatile organic compounds (VOCs) have shown distinct patterns in Crohn's disease (CD) and ulcerative colitis (UC). VOC productIon, reflecting gut fermentome metabolites, is perturbed in IBD. VOC sampling is non-invasive, with various compounds identified from faecal, breath and urine samples. This study aimed to determine if FAIMS (field asymmetric Ion Mobility Spectroscopy) analysis of exhaled VOCs could distinguish IBD from controls. Methods Seventy-six subjects were recruited, 54 established IBD (25 CD, 29 UC) and 22 healthy controls. End expiratory breath was captured using a Warwick device and analysed by FAIMS. Data were pre-processed using wavelet transformatIon, and classificatIon performed in a 10-fold cross-validatIon. Feature selectIon was performed using Wilcoxon rank sum test, and sparse logistic regressIon gave class predictIons, to calculate sensitivity and specificity. Results FAIMS breath VOC analysis showed clear separatIon of IBD from controls, sensitivity: 0.74 (0.65–0.82), specificity: 0.75 (0.53–0.90), AUROC: 0.82 (0.74–0.89), p -value 6.2 × 10 −7 . IBD subgroup analysis distinguished UC from CD: sensitivity of 0.67 (0.54–0.79), specificity: 0.67 (0.54–0.79), AUROC: 0.70 (0.60–0.80), p -value 9.23 × 10 −4 . ConclusIon This confirms the utility of exhaled VOC analysis to distinguish IBD from healthy controls, and UC from CD. It conforms to other studies using different technology, whilst affirming exhaled VOCs as biomarkers for diagnosing IBD.
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PWE-136 The non-invasive detectIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: a pilot study
Gut, 2015Co-Authors: James A. Covington, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, E. Westenbrink, Ramesh P. ArasaradnamAbstract:IntroductIon Non Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods, including that of the Fibroscan, have limitatIons, thus there is a clinical need for more robust, non-invasive screening tools. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns. These patterns are detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We aimed to determine if progressive fatty liver disease produced an altered VOC pattern in urine; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). Method 34 patients were recruited; 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40 ± 0.1°C and the headspace analysed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a ‘Random Forrest’ classificatIon algorithm and a 10 fold cross validatIon method was applied. Results Urinary VOCs could distinguish liver disease patients from controls with a sensitivity of 0.58 (0.33–0.88) but specificity of 0.93 (0.68 – 1.00); Area Under Curve (AUC) 0.73 (0.55 – 0.90). NASH/NASH-C was similarly separated from the NAFLD/control patients with a sensitivity of 0.73 (0.45–0.92), a specificity of 0.79 (0.54–0.94) and AUC of 0.79 (0.64–0.95), respectively. ConclusIon This pilot study offers the potential for early non-invasive tracking of liver disease using urinary VOC bio-odorant fingerprints to distinguish patients with a disease within the spectrum of fatty liver disease from healthy controls, but also to distinguish subsets of the spectrum from each other, such as NASH from NAFLD. This may develop into a viable alternative surveillance or diagnostic tool in patients unable or unwilling to undergo liver biopsy. Disclosure of interest None Declared.
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Non-invasive distinctIon of non-alcoholic fatty liver disease using urinary volatile organic compound analysis: early results.
Journal of gastrointestinal and liver diseases : JGLD, 2015Co-Authors: Ramesh P. Arasaradnam, Emma Daulton, Michael Mcfarlane, Nicola O'connell, Subiatu Wurie, Chuka U. Nwokolo, Karna Dev Bardhan, Richard S. Savage, Eric W. Westenbrink, James A. CovingtonAbstract:BACKGROUND & AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitatIons, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentatIon patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH). METHODS: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classificatIon algorithm and using a 10 fold cross validatIon method was applied. RESULTS: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 - 0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively. CONCLUSIonS: This pilot study suggests that urinary VOCs detectIon may offer the potential for early non-invasive characterisatIon of liver disease using 'smell prints' to distinguish between NASH and NAFLD.
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DetectIon of colorectal cancer (CRC) by urinary volatile organic compound analysis.
PloS one, 2014Co-Authors: Ramesh P. Arasaradnam, Michael Mcfarlane, Nicola O'connell, Samantha Chambers, Eric W. Westenbrink, Catherine Bailey, Matthew G. Thomas, Courtenay Ryan-fisher, Paula Hodges, Christopher HarmstonAbstract:Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of populatIon based FOBt testing in the UK is also low at around 50%. The detectIon of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extractIon from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detectIon with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using Ion Mobility Spectroscopy technology (FAIMS) with potential as a novel screening tool.
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PTH-187 A Novel Non-Invasive Approach to Diagnose Bile Acid Diarrhoea (Bad) using an Electronic Nose (E-Nose) and Field Asymmetric Ion Mobility Spectroscopy (Faims)
Gut, 2013Co-Authors: James A. Covington, Nicola O'connell, Chuka U. Nwokolo, Karna Dev Bardhan, Catherine Bailey, E Westinbrink, Matthew G. Thomas, J Cullis, Nigel Williams, Ramesh P. ArasaradnamAbstract:IntroductIon A third of diarrhoea predominant irritable bowel syndrome (D-IBS) results from bile acid malabsorptIon (BAM); diagnosed by 75 SeHCAT retentIon test. We have previously demonstrated the ability of using an E-nose and FAIMS to detect inflammatory bowel disease (IBD) by shifts in the patterns of volatile organic compounds (VOCs) in the gases and vapours that emanate from urine samples. Here, we have extended our work to detect BAM from urine odours alone. Methods Technology Principles - E-nose This uses an array of gas phase chemical sensors which are broadly tuned to different chemical groups. When a urine sample is presented to the sensor array, a unique response is produced. By taking all of the sensor responses together, a bio-odorant fingerprint is created. FAIMS operates on similar principles, but produces its fingerprint by measuring the differences in Mobility of Ionised chemicals in high electric fields. Subjects and patients BAM (7 day retentIon value of o C. The headspace (the air above the sample) was then pumped from the containers and analysed by an AlphaMOS FOX 4000 E-nose and FAIMS instrument. Discriminant FunctIon Analysis and Fisher Discriminant Analysis (FDA) were used for statistical evaluatIon, respectively. Results The FOX 4000 E-nose plot (Figure 1) shows separate and distinct groupings of patients with BAM, UC, and healthy controls. FAIMS analysis gave a broadly similar pattern (not shown). ConclusIon D-IBS related to BAM is a common conditIon and treatment with BA sequestrants is effective in the majority. The SeHCAT retentIon test makes diagnosis easy but is not available in all centres: our pilot data offers an alternative diagnostic approach with high potential. Disclosure of Interest None Declared.
