The Association of Chronic Exposure to Particulate Matter Air Pollutants, Inflammation, and Atherogenesis in At-Risk El Paso Children

描述（由申请人提供）：拟议的研究解决了提高对城市空气污染中存在的颗粒物质的短暂和长期暴露对儿童心血管健康的影响的理解的需要。具体来说，它将研究短暂暴露于高PM2.5和UFP水平会促进儿童氧化应激和全身性炎症的假设。该研究还将检验慢性PM暴露以动脉硬度和厚度增加的形式促进血管重塑（通过全身炎症）的假设。据推测，在其他促炎因素（如肥胖、高脂肪饮食、久坐不动）存在的情况下，PM暴露对心血管的不良影响会加速，而抗炎因素会起到减少这些影响的作用（如富含新鲜水果和蔬菜的饮食）。该研究将在居住在德克萨斯州埃尔帕索的300名儿童（7-11岁）中进行。美国10号州际公路是美墨边境的第二大入境口岸，其地理特征和存在以及200家工厂导致一些社区比其他社区污染严重。为了研究短暂暴露于环境PM2.5和UFP对健康儿童全身炎症指标的影响，我们将在三个（高、中、低PM）社区开展一项两波面板研究，通过hpCRP、IL-6、异前列腺素、ICAM-1、VCAM-1和p -选择素粘附分子来研究短暂暴露于PM2.5和UFP与炎症的关系。在两次炎症生物标志物抽血之前，将对每60天（前一天、2天、一周、一个月和2个月的平均值）进行5次累积暴露测量。将针对5种不同的暴露措施（前12、24、36、48和60个月）构建累积长期（5年）PM2.5和UFP暴露的时空模型。平均)。面板和长期PM研究的暴露模型将从位于三个目标社区的中央空气质量监测仪中构建。放置在学校外和社区战略地点的便携式PM监测器将用于确定PM的来源和组成。其他便携式监测仪放置在三所社区学校内，并从参与者及其家中随机抽取子样本，收集室内和个人PM暴露的数据。这些数据将用于调整PM暴露模型中的测量误差。多元统计模型还将考虑污染气体、天气条件和其他潜在协变量的贡献。为了研究长期暴露于高PM2.5和UFP是否与血管重塑指标相关，在第一阶段研究中，参与者还将接受超声检查。这些研究旨在研究慢性PM2.5和UFP暴露与血液内皮素-1水平、腹部（aIMT）和颈动脉（cIMT）内膜-中膜厚度测量的动脉增厚和动脉硬度（肱动脉血流介导的扩张）之间的关系。识别

DESCRIPTION (provided by applicant): The proposed study addresses the need for the improved understanding of the impact of transient and longer- term exposure to particulate matter present in urban air pollution on the cardiovascular health of children. Specifically, it wil investigate the hypothesis that transient exposure to high PM2.5 and UFP levels promotes oxidative stress and systemic inflammation in children. The study also will examine the hypothesis that chronic PM exposure promotes vascular remodeling (via systemic inflammation) in the form of increased arterial stiffness and thickness. It is hypothesized that the adverse cardiovascular effects of PM exposure will be accelerated in the presence of other pro-inflammatory factors (e.g., obesity, high fat diet, sedentarism) while anti-inflammatory factors wil act to reduce these (e.g., diet rich in fresh fruits and vegetables). The study will be conducted i 300 children (age 7-11 yrs) residing in the El Paso, Texas. The geographic characteristics, and presence of US Interstate 10, the second largest port of entry on the US-Mexico border and 200 factories cause some neighborhoods to be heavily polluted than others. To investigate the effects of transient exposure to ambient PM2.5 and UFP with systemic inflammation indicators in healthy children, a 2-wave panel study will be carried out in three (high, medium and low PM) neighborhoods to investigate the association of transient PM2.5 and UFP exposure with inflammation as measured by hpCRP, IL-6, isoprostane, ICAM-1, VCAM-1, and P-selectin adhesion molecules. Before each of the two inflammatory biomarker blood draws, five cumulative exposure measurements will be constructed for each prior 60-day period (prior day, 2-days, week, month, and 2-month average). Spatial-temporal models of cumulative long-term (5 yr) PM2.5 and UFP exposures will be constructed for five different exposure measures (prior 12, 24, 36, 48, and 60 mos. average). Exposure models for both panel and long-term PM studies will be constructed from central air quality monitors located in the three target neighborhoods. Portable PM monitors placed outside schools and in strategic neighborhood locations will be used to identify PM sources and composition. Other portable monitors placed inside the three neighborhood schools and from a random subsample of participants and their homes will collect data on indoor and personal PM exposure. These data will be used to adjust for measurement error in the PM exposure models. The multivariate statistical models will also consider the contributions of pollutant gases, weather conditions, and other potential covariates. To investigate whether chronic exposure to high PM2.5 and UFP is associated with indicators of vascular remodeling, during the first study wave, participants will also undergo ultrasound studies. These to examine the relationship of chronic PM2.5 and UFP exposure with blood endothelin-1 levels, arterial thickening measured by abdominal (aIMT) and carotid (cIMT) intima-media thickness and arterial stiffness (brachial artery flow-mediated dilation). To identify the elemental composition (e.g., hydrocarbons, quinines, light cations, heavy and transition metals) and sources of outdoor PM2.5 and UFP present within each of the three neighborhood zones, ambient PM samples will be collected over a 12- month period at the three participating schools, their surrounding neighborhoods, and in a random sample of participant homes. The samples will be analyzed using an automated energy dispersive XRF instrument. .