Non-invasive strategy in assessing asthma through biofluids metabolomics exploration: exhaled breath and urine potentialities

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.

WOW: wiki aided organization draWing

As the world evolves, organizations are becoming more and more complex, and the need to understand that complexity is increasing as well. With this demand, arises organizational engineering, which is a subject that emerged with the purpose to make organizations easier to understand, by putting in practice the concept of organizational self-awareness, which means that that the collaborators who are part of an organization, need to understand it and know what their role in it is. The DEMO methodology (Design Engineering Methodology for Organizations), came up with the purpose of representing these organizations’ self-awareness, through the definition and creation of consistent and coherent diagrams. Semantic wikis have features that can help in enterprise modelling. UEAOM (Universal Enterprise Adaptive Organization Model) is a model that allows the specification and dynamic evolution of languages, meta-models, models, and their representations as diagrams and tables. In this project, it was implemented a system based on UEAOM, and Semantic Media Wiki which allows a graphical creation and edition of diagrams. UEAOM can be divided into the meta-modeling level where a language is defined, and the modelling level where instances of classes of that language are created. The system we developed focuses on the modeling level, but will takes as a basis the project that focuses on meta-modeling. The DEMO language was used as an example for the implementation and tests of a graphical editor, based in web technologies and SVG, integrated with SemanticMediaWiki to allow an intuitive, coherent and consistent navigation and editing of organization diagrams.