Relationship Between Indoor Ultrafine Particle Exposure and Respiratory Morbidity, Inflammation, and Oxidative Stress in Children with Asthma. Particulate matter (PM) is a criteria pollutant, and exposures have been linked with acute and chronic health effects, including respiratory morbidity and mortality. The smallest form of PM, ultrafine PM (UFP), enters and disperses freely in the lungs, and can translocate into the bloodstream. Because of their small size, UFPs have an enormously large surface area:particle mass ratio and carry adsorbed toxic contaminants known to incite inflammatory and oxidative stress responses. They are hypothesized to be among the most harmful components of PM to human health, and yet few epidemiologic investigations have been completed due to limitations in monitoring capabilities only recently overcome. Furthermore, the sources of these particles are often unique, and indoor exposures (i.e. cooking, heating, environmental tobacco smoke) contribute heavily to individual exposure. Dr. Brigham, Assistant Professor in Pulmonary and Critical Care Medicine at Johns Hopkins University, has a strong interest in the effects of these particles on respiratory disease. She has extensive research experience in epidemiologic studies of asthma health and metabolic risk factors for asthma morbidity in both adult and pediatric populations, and conducts her research within a group combining resources from the Johns Hopkins School of Medicine and adjacent Bloomberg School of Public Health with the expertise to support indoor UFP monitoring. Dr. Brigham's proposal seeks to define the impact of indoor UFP exposure on children with asthma in Baltimore City, a uniquely susceptible population with a historically disproportionate burden of indoor air pollution and more than twice the national average of prevalent asthma. She proposes to investigate: (Aim 1) the effects of UFP exposure on pediatric asthma symptoms, lung function, and rescue-inhaler use, (Aim 2) the effects of UFP exposure on airway and systemic markers of oxidative stress and inflammation, and (Aim 3) mediation of the effects of UFP exposure on asthma health by additional modifiable metabolic factors known to affect response to larger PM: adiposity and dietary intake of omega-3 fatty acids. This award will not only provide an outstanding training vehicle for Dr. Brigham's development into an independent, NIH funded patient-oriented researcher, poised for leadership in investigations at the intersection of air pollution, metabolism, and respiratory health, but will also provide critically novel data regarding the impact of indoor UFP exposure in this vulnerable pediatric population.

PROJECT NARRATIVE Children and adults in the United States spend a majority of their time in the indoor home environment, and air pollution within this environment plays an important role in acute and chronic respiratory health effects. We know very little about one of the most potentially harmful components of air pollution, ultrafine particles, due to limitations in measurement and monitoring that have only recently been overcome. As a critical first step in understanding the effects of exposure to these small but important particles, this proposal monitors concentrations of ultrafine particles in the home, investigates the respiratory and systemic health effects experienced by children with asthma with known vulnerability to the effects of air pollution, and explores additional potential metabolic susceptibility factors that may be targeted in future studies to mitigate the effects of ultrafine particle exposure on health.