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.

Coaching or gaming? Implications of strategy choice for home based stroke rehabilitation

Background: The enduring aging of the world population and prospective increase of age-related chronic diseases urge the implementation of new models for healthcare delivery. One strategy relies on ICT (Information and Communications Technology) home-based solutions allowing clients to pursue their treatments without institutionalization. Stroke survivors are a particular population that could strongly benefit from such solutions, but is not yet clear what the best approach is for bringing forth an adequate and sustainable usage of home-based rehabilitation systems. Here we explore two possible approaches: coaching and gaming. Methods: We performed trials with 20 healthy participants and 5 chronic stroke survivors to study and compare execution of an elbow flexion and extension task when performed within a coaching mode that provides encouragement or within a gaming mode. For each mode we analyzed compliance, arm movement kinematics and task scores. In addition, we assessed the usability and acceptance of the proposed modes through a customized self-report questionnaire. Results: In the healthy participants sample, 13/20 preferred the gaming mode and rated it as being significantly more fun (p < .05), but the feedback delivered by the coaching mode was subjectively perceived as being more useful (p < .01). In addition, the activity level (number of repetitions and total movement of the end effector) was significantly higher (p <.001) during coaching. However, the quality of movements was superior in gaming with a trend towards shorter movement duration (p=.074), significantly shorter travel distance (p <.001), higher movement efficiency (p <.001) and higher performance scores (p <.001). Stroke survivors also showed a trend towards higher activity levels in coaching, but with more movement quality during gaming. Finally, both training modes showed overall high acceptance. Conclusions: Gaming led to higher enjoyment and increased quality in movement execution in healthy participants. However, we observed that game mechanics strongly determined user behavior and limited activity levels. In contrast, coaching generated higher activity levels. Hence, the purpose of treatment and profile of end-users has to be considered when deciding on the most adequate approach for home based stroke rehabilitation.