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Please use this identifier to cite or link to this item: https://dspace.lboro.ac.uk/2134/12415

Title: Prospecting for markers of disease in respiratory diseases
Authors: Guallar-Hoyas, Cristina
Keywords: Exhaled breath
Thermal desorption
Gas chromatography
Mass spectrometry
Multivariate analysis
Issue Date: 2013
Publisher: © Cristina Guallar Hoyas
Abstract: Asthma, current detection methods and metabolites proposed as asthma markers are described. The limitation of the disease diagnosis is outlined and metabolomics is introduced as the approach carried out within this research with the potential to measure the group metabolites that characterise the metabolic responses of a biological system to a specific disease. Chemistry underlying breathing, current breath collection and analytical techniques are described as well as detection and data processing technology associated within our research. A work-flow for the collection, analysis and processing of exhaled breath samples in respiratory diseases is described. The non-invasive sampling method allows collection of exhaled breath samples on children and adults without experiencing any discomfort. The analysis of exhaled breath samples using thermal desorption gas chromatography mass spectrometry outlines the use of retention index for the alignment of VOCs retention time shifting over time. This methodology enables the creation of a breath matrix for multivariate analysis data processing where each VOC is defined by retention index and most intense fragments of the mass spectrum. This methodology is tested in two cohorts of participants: paediatric asthma and severe asthmatic participants whose breath profiles are compared against healthy controls and within the two asthmatic phenotypes to prospect the markers that differentiate between the different groups. Eight candidate markers are identified to discriminate between asthmatic children and healthy children and seven markers between asthmatics undergoing therapy and healthy controls. The database from severe and paediatric asthma is compared, establishing seven non-age related markers between the two groups. A new interface is developed for the faster analysis of exhaled breath samples using thermal desorption ion mobility mass spectrometry. The interface front end has been modified and optimised to achieve the best sensitivity and resolution of VOCs in exhaled breath. A preliminary study carried out in a small cohort of volunteers shows the feasibility of the technique for the differentiation of asthmatic and healthy adults.
Description: A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University. Note that the published abstracts are in closed access in a separate file.
Sponsor: Loughborough University, Astra Zeneca
URI: https://dspace.lboro.ac.uk/2134/12415
Appears in Collections:PhD Theses (Chemistry)

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Form-2013-Guallar-Hoyas166.94 kBAdobe PDFView/Open
Published abstracts from Thesis-2013-Guallar-Hoyas.pdfClosed access946.49 kBAdobe PDFView/Open
Thesis-2013-Guallar-Hoyas.pdfOpen access5.2 MBAdobe PDFView/Open


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