Browsing by Subject "oxygen"

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    Dependence of Whole Blood Rheology on Oxygen Tension in Sickle Cell DIsease
    (2018-02) Lu, Xinran
    In sickle cell disease, oxygen tension plays a major role in dictating the mechanical function of single red blood cells. As oxygen tension decreases, cellular stiffness increases, to the point where the flow of whole blood can come to a compete occlusion. Unfortunately, there are also many unknowns in sickle cell disease, which is clinically expressed by the severe lack of approved treatment options for the disease. To solve many of these issues, we aim to expand our understanding of sickle cell disease by diving into the fundamental mechanisms by which the whole blood rheology becomes impaired in response to oxygen tension. Here, we use an in vitro disease model of sickle cell rheology, built within a microfluidic platform, to simulate whole blood flow within the microvasculature. We first report on the relationship between whole blood rheology and oxygen tension in sickle cell disease under steady state conditions and map out the specific oxygen tension where rheological impairment of blood flow begins. We then report on this measurement in both sickle cell trait (the heterozygous carrier state of sickle cell disease) as well as transfusion therapy in sickle cell disease, where we find and report on the rheological differences compared to native sickle cell disease. Next, we modify our microfluidic disease model to investigate the temporal and spatial dynamics of sickle cell disease by creating a microvascular capillary tree design couple to physiologically relevant oxygen tension gradients. Finally, we revisit the specific response of whole blood rheology as a function of oxygen tension by mapping out the velocity gradients and velocity profiles of blood flow, where we find characteristic differences in velocity profile shapes relative to oxygen.
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    Health-related Quality of Life and its Associated Variables among Individuals with Idiopathic Pulmonary Fibrosis
    (2019-09) Bors, Melinda
    Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a median survival of only three to five years from the time of diagnosis, with no known cure, or treatment to extend survival. Due to a lack of clinical studies, large gaps remain in understanding how IPF affects health-related quality of life (HRQOL). Because of the terminal nature of IPF, an improved understanding of how this disease affects patients' lives is needed. The works presented in this dissertation revealed that individuals with IPF are at greater risk for cognitive abnormalities, and confirmed that they are more likely to have depressive symptoms, and worsened HRQOL. The pathways among the variables cannot be easily elucidated, especially the co-existence of depressive symptoms and cognitive impairment. Nonetheless, the presence of depressive symptoms should not be overlooked in research or in clinical management, as depression may be associated with dyspnea, the symptom most commonly found to be responsible for the compromised HRQOL seen in IPF, and could be of increased interest if treating the depression could result in the alleviation of dyspnea and amelioration of HRQOL. The significance of the cognitive impairment observed among individuals with IPF remains unclear, both for selecting therapies and anticipating expected treatment outcomes. Further research is needed to understand if exertional hypoxia is related to the cognitive abnormalities noted in cases of severe IPF, or if there are long term benefits to correcting exertional hypoxia. Patient reported outcomes and HROQL data assist clinicians by providing insight from the patient’s perspective about the level of illness burden and the effectiveness of a given intervention. Understanding which measures of health are most valued by patients is critical when establishing a plan of care, especially if asking patients to comply with a burdensome therapy such as ambulatory oxygen (AO). The role of AO in treating exertional hypoxia in IPF is obscure and more data are needed about its impact on disease progression, and HRQOL. Determining which variables are associated with HRQOL may facilitate clinician and patient interpretation of disease progression and the effects of therapy.