Antioxidant Interventions And Pulmonary Outcomes: The Impact Of Nutrition And Gene Expression On The Lung

Abstract

The aims of this research were to determine how gene expression and chronic obstructive pulmonary disease (COPD) susceptibility are related to antioxidant nutritional status and to determine if antioxidant supplementation prevents COPD disease processes. Although cigarette smoking is the primary risk factor for COPD a minority of smokers develop disease thus other factors must play a role in disease susceptibility and progression. The studies conducted for this dissertation address the hypotheses that dietary supplementation with antioxidant vitamins can augment the lung's antioxidant defenses thereby preventing disease development and that antioxidant-related genes are dysregulated by COPD disease processes. The first project was a large-scale randomized clinical intervention trial of vitamin E dietary supplements in which the association of supplementation and risk of COPD was assessed. Women randomly assigned to take vitamin E supplements during a 10-year intervention were 10% less likely to develop COPD during the study period. The effect of the intervention was similar in both smokers and non-smokers and was not changed by other factors measured in the study. The second study was a small-scale clinical intervention trial that investigated how antioxidant supplementation altered concentrations of nutrients systemically and in the lung compartment. For intervention trials assessing whether the supplement is reaching the target tissue is critical and no prior studies show direct evidence that supplemental antioxidants reach the lung. In this study bronchioalveolar lavage fluid concentrations of vitamin E and selenium were measured before and after intervention with vitamins E and C and selenium and nutrient concentration increased in response to supplementation, providing evidence that antioxidant supplements were delivered to the lung where they could combat oxidative stress that causes lung tissue damage. The third study assessed antioxidant status in plasma and lung tissue and gene expression in lung tissue of COPD patients with different levels of disease severity. Twelve antioxidant-related genes were differentially expressed in patients with more severe disease. Taken together the findings from these studies suggest that intervention with antioxidant nutrients increases lung nutrient status and decreases COPD risk and the mechanism may be in part modulation of antioxidant-related gene expression.