Healthcare costs are escalating in the U.S., with a projected 48 trillion dollars by 2021. More than ever medical researches are obligated to ensure that costly treatment modalities are safe and effective. Chronic obstructive pulmonary disease (COPD) is a costly and debilitating disease, ranked as the third leading cause of death in America. Currently, treatment for COPD consists of anti-inflammatory agents, bronchodilators, antibiotics and supplemental oxygen when hypoxemia or clinical manifestations ensue. Oxidative stress is central to the pathology of COPD. Supplemental oxygen has been substantiated as an instigator of oxidative stress; however, LFDO has not been evaluated as a mechanism of ongoing oxidative stress in individuals with COPD. Isofuran (IsoF), a biosynthetic relative of the validated oxidative stress biomarker 8-isoprostane, is preferentially synthesized during periods of increased tissue oxygen tension. This sort of specificity allows for refinement in the assessment of supplemental oxygen as a source of oxidative stress. To address this potential this study evaluated individuals diagnosed with COPD utilizing LFDO. The study also aimed to determine if IsoF possessed clinical application in predicting the standard pulmonary function test (PFT) parameters of FEV1, FVC, FEV1/FVC and FEF25-75. The exhaled breath condensate (EBC) of 52 individuals with COPD was evaluated for the presence of IsoF. An active control group not receiving LFDO (n=26) was compared to an active treatment group receiving LFDO for a minimum of 6 hrs/day (n=26). The groups showed no statistically significant demographic differences in age, gender, height, weight, ethnicity or smoking history or in the pulmonary function test parameters of FEV1, FVC, and FEV1/FVC, with the exception of the FEF25-75 (P=0.03). The active control group generated a mean EBC IsoF level of 35.81 ± 4.91 pg/ml (± SEM) compared to the active treatment group mean EBC IsoF level of 51.37 ± 8.27 pg/ml (P=0.057). Currently, no research has been conducted that defines baseline EBC IsoF levels in healthy or diseased lungs. No statistically significant differences in mean EBC IsoF levels were noted between the control and treatment groups; however, the results, in conjunction with the only two studies available utilizing EBC IsoF as an oxidative stress biomarker, may serve to provide benchmark information for future research regarding individuals with diseased lungs, specifically COPD.

Multiple biomarkers of oxidative stress have been measured and used in human medicine to diagnose and monitor airway disease. The purpose of the study was to determine if similar relationships existed between inflammatory and oxidative stress biomarkers in exhaled breath condensate (EBC), bronchoalveolar lavage fluid (BALF), red blood cells, white blood cells, and plasma; and cytokine expression in airway inflammatory cells and mucosal biopsies of RAO-affected horses and their controls. Sixteen horses in pairs were used: 8 non-RAO-affected (controls) and 8 RAO-affected horses. Samples from all horses were collected at remission (S1), during environmental challenge (S2) and at recovery (S3). RAO-affected horses had significant alterations in cellular glutathione peroxidase (cGPx) activity, ascorbic acid and pH in a number of biological samples. Concentrations of 8-isoprostanes, isofurans, amino acids and mRNA expression of interleukin 4 (IL4), gamma interferon (INFγ), inducible nitric oxide synthase (iNOS), extracellular glutathione peroxidase (GPx-3), and cytosolic superoxide dismutase (SOD-1) were not significantly different or were at the limits of detection. Conductivity was measured and assessed as a potential correctional factor for respiratory fluid dilution. The alterations in biomarker concentrations demonstrate that oxidative stress is an important component of airway inflammation in RAO-affected horses. Further research is warranted in the use of biomarkers and the effects of dietary interventions. / Master of Science