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

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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.