Publication
Non-invasive strategy in assessing asthma through biofluids metabolomics exploration: exhaled breath and urine potentialities
| dc.contributor.advisor | Câmara, José Sousa | |
| dc.contributor.advisor | Carriço, Sílvia Maria da Rocha Simões | |
| dc.contributor.author | Caldeira, Michael Manuel Lima | |
| dc.date.accessioned | 2015-09-25T09:07:54Z | |
| dc.date.available | 2015-09-25T09:07:54Z | |
| dc.date.issued | 2015-06 | |
| dc.date.submitted | 2015-09-25 | |
| dc.description.abstract | Asthma is a significant health issue in the pediatric population with a noteworthy growth over the years. The proposed challenge for this PhD thesis was the development of advanced methodologies to establish metabolomic patterns in urine and exhaled breath associated with asthma whose applicability was subsequently exploited to evaluate the disease state, the therapy adhesion and effect and for diagnostic purposes. The volatile composition of exhaled breath was studied combining headspace solid phase microextraction (HS-SPME) with gas chromatography coupled to mass spectrometry or with comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high resolution time of flight analyzer (GC×GC–ToFMS). These methodologies allowed the identification of several hundred compounds from different chemical families. Multivariate analysis (MVA) led to the conclusion that the metabolomic profile of asthma individuals is characterized by higher levels of compounds associated with lipid peroxidation, possibly linked to oxidative stress and inflammation (alkanes and aldehydes) known to play an important role in asthma. For future applications in clinical settings a set of nine compounds was defined and the clinical applicability was proven in monitoring the disease status and in the evaluation of the effect and / or adherence to therapy. The global volatile metabolome of urine was also explored using an HSSPME/GC×GC–ToFMS method and c.a. 200 compounds were identified. A targeted analysis was performed, with 78 compounds related with lipid peroxidation and consequently to oxidative stress levels and inflammation. The urinary non-volatile metabolomic pattern of asthma was established using proton nuclear magnetic resonance (1H NMR). This analysis allowed identifying central metabolic pathways such as oxidative stress, amino acid and lipid metabolism, gut microflora alterations, alterations in the tricarboxylic acid (TCA) cycle, histidine metabolism, lactic acidosis, and modification of free tyrosine residues after eosinophil stimulation. The obtained results allowed exploring and demonstrating the potential of analyzing the metabolomic profile of exhaled air and urine in asthma. Besides the successful development of analysis methodologies, it was possible to explore through exhaled air and urine biochemical pathways affected by asthma, observing complementarity between matrices, as well as, verify the clinical applicability. | por |
| dc.identifier.tid | 101258798 | |
| dc.identifier.uri | http://hdl.handle.net/10400.13/868 | |
| dc.language.iso | eng | por |
| dc.relation | European Regional Development Fund (FEDER) through the Competitive Factors Thematic Operational Programme (COMPETE) | por |
| dc.relation | 2013 - Strategic Project | |
| dc.relation | DESENVOLV. DE UMA METODOLOGIA PARA A DETECÇÃO DE BIOMARCADORES DE DOENÇAS RESPIRATÓRIAS ALÉRGICAS BASEADA NA APLICAÇÃO DA MICROEXTRACÇÃO EM FASE SÓLIDA ACOPLADA A CROMATOGRAFIA EM FASE GASOSA. CONTRIBUTOS PARA A DEFINIÇÃO DE UM MEIO DIAGNÓSTICO | |
| dc.relation | ASTHMA - Future asthma management helped by non-invasive sampling: contributes for the definition of a rapid and non-invasive diagnostic tool | |
| dc.relation | Strategic Project - UI 674 - 2011-2012 | |
| dc.subject | Asthma | por |
| dc.subject | Exhaled breath | por |
| dc.subject | Urine | por |
| dc.subject | Metabolomics | por |
| dc.subject | GCxGC-ToFMS | por |
| dc.subject | 1H NMR | por |
| dc.subject | Chemistry, speciality in Analytical Chemistry | por |
| dc.subject | . | por |
| dc.subject | Centro de Ciências Exatas e da Engenharia | por |
| dc.title | Non-invasive strategy in assessing asthma through biofluids metabolomics exploration: exhaled breath and urine potentialities | por |
| dc.type | doctoral thesis | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | 2013 - Strategic Project | |
| oaire.awardTitle | DESENVOLV. DE UMA METODOLOGIA PARA A DETECÇÃO DE BIOMARCADORES DE DOENÇAS RESPIRATÓRIAS ALÉRGICAS BASEADA NA APLICAÇÃO DA MICROEXTRACÇÃO EM FASE SÓLIDA ACOPLADA A CROMATOGRAFIA EM FASE GASOSA. CONTRIBUTOS PARA A DEFINIÇÃO DE UM MEIO DIAGNÓSTICO | |
| oaire.awardTitle | ASTHMA - Future asthma management helped by non-invasive sampling: contributes for the definition of a rapid and non-invasive diagnostic tool | |
| oaire.awardTitle | Strategic Project - UI 674 - 2011-2012 | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FQUI%2FUI0062%2F2013/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBD%2F40374%2F2007/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FQUI-QUI%2F117803%2F2010/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI0674%2F2011/PT | |
| oaire.fundingStream | 6820 - DCRRNI ID | |
| oaire.fundingStream | PIDDAC | |
| oaire.fundingStream | 5876-PPCDTI | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| person.familyName | Caldeira | |
| person.givenName | Michael | |
| person.identifier.orcid | 0000-0001-5371-7281 | |
| person.identifier.rid | A-2461-2013 | |
| person.identifier.scopus-author-id | 16300962200 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | openAccess | por |
| rcaap.type | doctoralThesis | por |
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| thesis.degree.discipline | Chemistry specialty in Analytical Chemistry | por |
| thesis.degree.level | Doutor | por |
| thesis.degree.name | Doctorate in Chemistry specialty in Analytical Chemistry | por |