The Association of Chronic Exposure to Particulate Matter Air Pollutants, Inflamm

说明(由申请者提供)：拟议的研究涉及需要更好地了解城市空气污染中存在的短暂和长期暴露于颗粒物对儿童心血管健康的影响。具体地说，它将调查这一假设，即短暂暴露于高PM2.5和UFP水平会促进儿童的氧化应激和全身炎症。这项研究还将检验这一假说，即慢性PM暴露通过增加动脉僵硬和厚度的形式促进血管重塑(通过全身炎症)。据推测，在其他促炎因素(如肥胖、高脂肪饮食、久坐不动)的存在下，PM暴露对心血管的不良影响将会加速，而抗炎因素将起到减少这些影响的作用(例如，富含新鲜水果和蔬菜的饮食)。这项研究将对居住在德克萨斯州埃尔帕索的300名儿童(7-11岁)进行。美国10号州际公路是美墨边境的第二大入境口岸，有200家工厂，其地理特征和存在导致一些社区的污染比其他社区严重。为探讨瞬时暴露于周围PM2.5和UFP对健康儿童全身炎症指标的影响，将在三个社区(高、中、低PM)进行两波小组研究，以调查瞬时PM2.5和UFP暴露与炎症之间的关系，检测hpCRP、IL-6、异前列腺素、ICAM-1、VCAM-1和P-选择素黏附分子。在两个炎性生物标志物抽血之前，将为之前的每个60天期间(前一天、两天、一周、一个月和两个月的平均值)构建五个累积暴露测量。将为五种不同的暴露措施(前12、24、36、48和60个月)构建长期(5年)PM2.5和UFP累积暴露的时空模型。平均值)。小组和长期PM研究的暴露模型将由位于三个目标社区的中央空气质量监测仪构建。放置在学校外和重要社区位置的便携式PM监测器将用于确定PM的来源和组成。其他放置在附近三所学校内的便携式监测仪，以及从参与者和他们的家中随机抽样的监测仪，将收集室内和个人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。多变量统计模型还将考虑污染物气体、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，在第一波研究中，参与者还将接受超声研究。这些研究旨在研究慢性PM2.5和UFP暴露与血内皮素-1水平、腹部动脉增厚(AIMT)和颈动脉(CIMT)内膜-中层厚度以及动脉僵硬(肱动脉血流介导的扩张)的关系。要确定 根据三个居民区的元素组成(例如碳氢化合物、奎宁、轻阳离子、重金属和过渡金属)以及室外PM2.5和UFP的来源，将在12个月的时间内在三个参与学校及其周围社区和随机抽样的参与家庭中收集环境PM样本。样品将使用自动能量色散XRF仪器进行分析。。

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. .