There is a pressing need to establish novel biomarkers to predict the progression of thoracic aortic aneurysm (TAA) dilatation. Aside from hemodynamics, the roles of oxygen (O2) and nitric oxide ... Show moreThere is a pressing need to establish novel biomarkers to predict the progression of thoracic aortic aneurysm (TAA) dilatation. Aside from hemodynamics, the roles of oxygen (O2) and nitric oxide (NO) in TAA pathogenesis are potentially significant. As such, it is imperative to comprehend the relationship between aneurysm presence and species distribution in both the lumen and aortic wall. Given the limitations of existing imaging methods, we propose the use of patient-specific computational fluid dynamics (CFD) to explore this relationship. We have performed CFD simulations of O2 and NO mass transfer in the lumen and aortic wall for two cases: a healthy control (HC) and a patient with TAA, both acquired using 4D-flow magnetic resonance imaging (MRI). The mass transfer of O2 was based on active transport by hemoglobin, while the local variations of the wall shear stress (WSS) drove NO production. Comparing hemodynamic properties, the time-averaged WSS was considerably lower for TAA, while the oscillatory shear index and endothelial cell activation potential were notably elevated. O2 and NO showed a non-uniform distribution within the lumen and an inverse correlation between the two species. We identified several locations of hypoxic regions for both cases due to lumen-side mass transfer limitations. In the wall, NO varied spatially, with a clear distinction between TAA and HC. In conclusion, the hemodynamics and mass transfer of NO in the aorta exhibit the potential to serve as a diagnostic biomarker for TAA. Furthermore, hypoxia may provide additional insights into the onset of other aortic pathologies. Show less
Around 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent... Show moreAround 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent exacerbations or persistent airflow limitation. This thesis focuses on the mechanisms that may explain why these patients become difficult-to-treat and investigate biomarkers that can predict the development of specific asthma phenotypes. The different studies describe the possible role of alpha- antitrypsin in the development of persistent airflow limitation, the relationship between severity of asthma and the degree of peripheral airway inflammation and dysfunction, the clinical and inflammatory characteristics of obese patients with difficult-to-treat asthma, risk factors of lung function decline and the consistency of the eosinophilic phenotype Show less
