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

描述(由申请人提供)：本申请是一份修订的新研究人员(NIEHS PA-06-181)发起的开发/探索性研究提案(R21)，旨在解决了解短暂和长期颗粒物暴露对儿童全身炎症、氧化应激和动脉粥样硬化的影响的必要性。尸检和超声波研究表明，动脉粥样硬化的形成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人的全身炎症和血管重塑。然而，先前的研究还没有调查PM暴露对儿童全身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，甚至是随着时间的推移，脂肪条纹沉积和动脉增厚的微小但渐进性增加，都会导致更早的临床疾病发作。本研究将探讨这样一种假设，即儿童短暂暴露于高PM10和PM2.5水平会促进全身炎症、氧化应激和血管重塑。它还将调查PM的来源和元素组成，以更好地了解它们的炎症潜力。这项研究将对居住在基多大都市区(QMD)的300名儿童(7-12岁)进行，QMD是一个污染严重的高海拔城市，社区之间有明显的PM梯度。高海拔环境空气中O2含量的减少也会增加PM的暴露，这是因为呼吸频率增加。将在三个社区(高、中、低PM)进行一项短期(12个月)的双波小组研究，以调查瞬时PM2.5和PM10暴露与炎症之间的关系，如hpCRP、IL-6、ICAM、VCAM和E-选择素细胞黏附分子。在小组研究中抽取两个炎性生物标志物血液之前，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。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与腹部(AIMT)和颈动脉(CIMT)内膜-中层厚度测量的动脉增厚的关系。还将使用时空方法来模拟长期(5年)PM2.5和PM10的累积暴露。5年的滞后将被用来构建五种不同的风险敞口衡量标准：之前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暴露模型将根据位于三个目标社区的中央空气质量监测仪收集的数据构建。便携式PM监测仪将放置在学校外和重要的社区位置，用于确定PM的来源和元素组成。其他便携式监测仪将用于从三所学校内部以及从科目家庭和科目的随机抽样中收集室内和个人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。多变量统计模型还将考虑污染物气体、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/发育性R21研究将调查一种假设，即长期暴露于环境空气污染中的颗粒物(PM)的高海拔儿童(7-12岁)会发生全身炎症和氧化应激，导致动脉壁增厚，这可以通过m型超声波测量。这项研究还将检查PM中发现的可能导致炎症的元素。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.