Exposure to Ambient Air Pollution and Potential Biological Mechanisms/Biomarkers in Minority Children with Asthma Living in the United States

Rationale: Exposure to ambient air pollution is a major environmental risk factor for chronic diseases such as asthma. Children with asthma can be even more susceptible to the effects of air pollution since their respiratory system is not fully developed and some of the air pollutants can trigger asthma attacks. Over the past decades, scientists and researchers recognized the need to improve our understanding in the biological response mechanisms. The exact underlying mechanisms linking air pollution to disease outcomes, however, are not clear./nObjectives: The overarching aims of this thesis are to investigate the association between exposure to ambient air pollutants and adverse health effects among minority children and identify potential biological pathways from exposure to health end points by considering genetic ancestry and, asthma endotype (atopy) as effect modifiers of the relation between air pollution and telomere length. In Chapter 1, we investigated the association between ambient air pollutants and asthma exacerbations in urban minority children, as well as effect modification by atopy status and African ancestry. In Chapter 2, we conducted a pilot study to gather preliminary information about how telomere length varies in relation to polycyclic aromatic hydrocarbons (PAH) exposure in children living in a highly polluted city. In Chapter 3, we examined the association between ambient air pollutants and telomere length in minority children to understand the potential damage caused by air pollution at the molecular level./nMethods: In Chapter 1, air pollutant exposures were estimated based on residence using U.S. EPA monitoring data and inverse distance weighting. The associations between average daily exposures and asthma exacerbations were estimated by the incident rate ratio (IRR) from a negative binomial regression model. In Chapter 2, we selected asthmatic and non-asthmatic subjects based on their annual average PAH level and described patterns of telomere length, measured by using uniplex polymerase chain reaction (PCR). In Chapter 3, the annual average daily exposure to each of four air pollutants was examined in relation to telomere length./nResults: In chapter 1, exposure to ambient O3 and NO2 were associated with asthma exacerbations. Results for PM2.5 were null. Exposure-response relationships were linear for O3 and NO2 among non-atopic subjects and inconsistent among atopic subjects. Effect modification by African genetic ancestry was present only for O3; the impact of exposure appeared to be larger for those with higher African ancestry. In chapter 2, we found an inverse linear relationship between PAH and telomere length in a small pilot study. In chapter 3, the association between ambient SO2 and telomere length was significantly negative, whereas results for PM2.5, NO2 and O3 were null./nConclusions: Our results provide further evidence that exposure to ambient air pollution is a serious environmental risk factor that causes adverse health outcomes among minority children.

Advisor: Eisen, Ellen