Air Pollution, Systemic Inflammation, and Sub-Clinical Atherosclerosis in High-Al

描述（由申请人提供）：本申请是一份经过修订的新研究者（NIEHS PA-06-181）发起的发展性/探索性研究提案（R21），旨在了解儿童短暂和长期颗粒物暴露对全身炎症、氧化应激和动脉粥样硬化的影响。尸检和超声研究表明，动脉粥样硬化在生命早期就开始了。新出现的证据表明，暴露在PM2.5、PM10或汽车尾气中会促进易感动物和成年人的全身炎症和血管重塑。然而，先前的研究尚未调查PM暴露对儿童全身性炎症和动脉粥样硬化的潜在影响。这是一个重要的研究方向，因为慢性炎症，甚至随着时间的推移，脂肪条纹沉积和动脉增厚的微小但进行性增加都可能导致临床疾病的早期发作。本研究将探讨短暂暴露于高环境PM10和PM2.5水平会促进儿童全身性炎症、氧化应激和血管重构的假设。它还将调查PM来源和元素组成，以便更好地了解它们的炎症潜力。该研究将在基多大都市区（QMD）的300名儿童（7-12岁）中进行，基多大都市区是一个严重污染的高海拔城市，各社区之间的PM梯度明显。高海拔地区环境空气中氧含量的降低也会增加呼吸频率导致的PM暴露。一项短期（12个月）的两波面板研究将在三个（高、中、低PM）社区进行，通过hpCRP、IL-6、ICAM、VCAM和e -选择素细胞粘附分子来研究短暂的PM2.5和PM10暴露与炎症的关系。在小组研究中的两次炎症生物标志物抽血之前，将为每60天（前一天、2天、一周、一个月和2个月的平均值）构建5次累积暴露测量。在第一波期间，受试者还将接受超声研究，以检查长期暴露于PM2.5和PM10与动脉增厚的关系，这是通过腹部（aIMT）和颈动脉（cIMT）内膜-中膜厚度测量的。还将使用时空方法来模拟PM2.5和PM10的累积长期（5年）暴露。5年滞后将用于构建五种不同的暴露度量：前12个月、24个月、36个月、48个月和60个月的平均值。小组和长期PM研究的PM暴露模型将根据从位于三个目标社区的中央空气质量监测器收集的数据构建。放置在学校外和社区战略地点的便携式PM监测仪将用于识别PM来源和元素组成。其他便携式监测仪将用于收集来自这三所学校内部以及来自受试者家庭和受试者的随机子样本的室内和个人PM暴露数据。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、海拔和其他潜在协变量的贡献。公共卫生相关性：探索性/发展性R21研究将调查一种假设，即生活在高海拔地区的儿童（7-12岁）长期暴露于环境空气污染中的颗粒物（PM）中，会发生全身性炎症和氧化应激，导致动脉壁增厚，这可以用m型超声测量。该研究还将检查PM中可能引起炎症的元素。这些发现将被用来为未来更全面的研究提供信息，这些研究需要为高危人群制定有效的公共卫生计划。

DESCRIPTION (provided by applicant): This application is a revised new investigator (NIEHS PA-06-181) initiated developmental/exploratory research proposal (R21) that addresses the need for understanding the impact of transient and long-term particulate matter exposure on systemic inflammation, oxidative stress and atherogenesis in children. Autopsy and ultrasound studies have shown that atherogenesis begins early in life. Emerging evidence suggests that exposure to PM2.5, PM10 or vehicle exhaust promotes systemic inflammation and vascular remodeling in susceptible animals and adults. However, prior studies have not investigated the potential effects of PM exposure on systemic inflammation and atherogenesis in children. This is an important line of inquiry since chronic inflammation and even small but progressive increases in fatty streak deposition and arterial thickening over time can lead to an earlier onset of clinical disease. The present study will investigate the hypothesis that transient exposure to high ambient PM10 and PM2.5 levels promotes systemic inflammation, oxidative stress, and vascular remodeling in children. It also will investigate PM sources and elemental composition in order to better understand their inflammatory potential. The study will be conducted in 300 children (age 7-12 yrs) residing in the Quito Metropolitan District (QMD), a heavily polluted, high altitude city that has distinct PM gradients among neighborhoods. The reduced O2 content of ambient air at high altitude causes also increases exposure to PM resulting from increased respiratory frequency. A short- term (12 mo) two-wave panel study will be carried out in three (high, medium and low PM) neighborhoods to investigate the association of transient PM2.5 and PM10 exposure with inflammation as measured by hpCRP, IL-6, ICAM, VCAM, and E-selectin cell adhesion molecule. Before each of the two inflammatory biomarker blood draws in the panel study, five cumulative exposure measurements will be constructed for each prior 60-day period (prior day, 2-days, week, month, and 2-month average). During the first wave, subjects also will undergo ultrasound studies to examine the relationship of long-term PM2.5 and PM10 exposure with arterial thickening as measured by abdominal (aIMT) and carotid (cIMT) intima- media thickness. A spatio-temporal approach also will be used to model cumulative long-term (5 yr) PM2.5 and PM10 exposures. The 5-year lag will be used to construct five different exposure measures: average of prior 12, 24, 36, 48, and 60 months. The PM exposure models for both the panel and long-term PM studies will be constructed from data collected 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 elemental composition. Other portable monitors will be used to collect indoor and personal PM exposure data from inside the three schools and from a random subsample of subject homes and subjects. 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, altitude, and other potential covariates. PUBLIC HEALTH RELEVANCE: The exploratory/developmental R21 study will investigate the hypothesis that children (7-12 years) living at high altitude who are exposed long-term to particulate matter (PM) in ambient air pollution develop systemic inflammation and oxidative stress leading to arterial wall thickening that can be measured with m-mode ultrasound. The study also will examine the elements found in PM that may cause inflammation. The findings will be used to inform more comprehensive future studies needed for the development of effective public health programs for at-risk populations.