The proposed project promises to be a rich training experience that will allow me to develop the skills necessary for clinical research. It achieves this through a combination of a rigorous research plan, relevant coursework, and supervised dedicated mentorship. Below is a summary of the research proposal. The urban minority pediatric population in the United States has a disproportionate burden of asthma. Several factors may contribute to this disparity, including high exposure to environmental pollutants and allergens, a poor diet, and other disadvantages of poverty. Recent attention has focused on the antioxidant and immune-modulatory role of vitamin D which may confer a protective effect on disease morbidity, and several clinical observational and cross-sectional studies support that low vitamin D levels may lead to greater allergic and asthma manifestations. Epidemiological studies, including our own preliminary investigations in Baltimore, have discovered that a significant proportion of African-American inner-city children with asthma have well below the recommended levels of serum vitamin D, and that, in these same children, indoor particulate matter (PM) is a significant cause of asthma morbidity. We therefore propose to determine whether lowerlevels of vitamin D, in such a highly-affected and vulnerable population, may increase their susceptibility to inhaled pollutants. To achieve this goal, we will nest this proposed study within an existing grant (The Center for Childhood Asthma in the Urban Environment DISCOVER # 1P50ES015903), which is currently recruiting 130 predominantly-black children with asthma, ages 5-12 years, in urban Baltimore to study the mechanisms by which air pollution induces lung inflammation and oxidative stress. This project proposal has three novel aims. First, to better understand the relationship between vitamin D levels and asthma health, we will be repeatedly measuring each subject's serum vitamin D levels, daily asthma symptoms and medication use, and twice-daily lung function during 4 one-week periods in each season of the year. Second, to determine if varying levels of vitamin D modify the inflammatory response to air pollution, we will also be monitoring each child's personal exposure to environmental PM throughout the day and simultaneously be measuring biomarkers of oxidative stress and inflammation present in blood, urine, and nasal lavage fluid. Finally, we will be collecting information regarding sun exposure, skin type, and dietary intake in order to assess the determinants of vitamin D status in this chronically low population, in preparation for future public health strategies directed towards improving asthma health.
Asthma attacks are particularly severe among urban African-American children and account for significant personal, economic, and social costs. Recent studies show that the majority of these children have low blood levels of vitamin D, and that the lower their levels, the worse their asthma symptoms seem to be. We would like to understand if low vitamin D levels put children at increased risk to be affected by common environmental triggers;if true, then improving their vitamin D status may ultimately protect urban minority children from a high burden of disease.
