Vascular toxicities of environmental tobacco particulates in children

描述（由申请人提供）：环境烟草烟雾（ETS）与成人心血管疾病之间的联系已得到证实。许多形式的慢性心血管疾病始于儿童期和/或青年期，美国至少有四分之一的儿童暴露于ETS。除了ETS之外，儿童超重和肥胖（影响约三分之一的儿科人口）是与成年期心血管疾病相关的重要独立危险因素。最近几项针对成年人类和动物的研究表明，肥胖是一种慢性全身性炎症，导致代谢和心血管后果。虽然ETS、肥胖和炎症在儿童中经常共存，但它们之间的关系及其对成人疾病前血管功能的影响尚未得到解决。我们的假设是肥胖加剧了ETS引起的炎症、内皮功能障碍和氧化应激，并影响了儿童的血管功能。总体目标是通过研究心血管疾病的早期发展，特别是在ETS存在的情况下，改善儿童和成人的健康。我们的目标是：验证ETS诱导的儿童血管功能障碍在肥胖的情况下被放大的假设。将招募9-18岁接触和未接触ets的儿童。BMI正常（每年龄<85%）和BMI升高（每年龄≥95%）的儿童将被平行研究。前臂血流量（FBF）将通过体积描记术确定，作为体内内皮功能的评估。血管性能将被研究与血管反应、血脂、炎症标志物、脂联素、氧化应激和内皮损伤的关系。2. 测试假设内皮祖细胞（EPC）的循环水平可以通过儿童暴露于ETS来预测，而肥胖会放大这种影响。流式细胞术将测定正常体重和肥胖青少年（暴露于和未暴露于ETS）的EPC计数。EPC浓度与血管反应、血脂、炎症标志物、脂联素、氧化应激和内皮损伤有关。暴露程度和持续时间与测量终点之间的关系将通过协变量回归分析和初步结构方程模型确定。根据这项研究，确定儿童心血管疾病多危险因素（ETS和肥胖）的关系和机制将对儿童和成人健康具有重要意义。公共卫生相关性：环境烟草烟雾（ETS）与成人头号杀手心脏病之间的科学联系已得到充分证实。儿童时期接触辐射辐射与心脏和血管损伤之间的关系尚未得到研究。与此同时，儿童肥胖最近被描述为“新千年的新流行病”，对心脏健康也有负面影响。本研究的目的是确定ETS、肥胖和儿童血管功能之间的关系。这项研究的结果将对儿童和成人的健康产生重大影响。

DESCRIPTION (provided by applicant): Links between environment tobacco smoke (ETS) and cardiovascular diseases in adults are well established. Many forms of chronic cardiovascular disease are initiated in childhood and/or young adulthood, and at least one quarter of children in the United States are exposed to ETS. In addition to ETS, childhood overweight and obesity (affecting about one-third of the pediatric population) is an important independent risk factor associated with cardiovascular disease in adulthood. Several recent studies in adult humans and animals suggest that obesity is a setting of chronic systemic inflammation, leading to metabolic and cardiovascular consequences. Although ETS, adiposity and inflammation often co-exist in children, their relationships and their impact on vascular performance prior to adult disease have not been addressed. Our hypothesis is that inflammation, endothelial dysfunction and oxidative stress caused by ETS are potentiated by obesity and effect vascular function in children. The overall goal is to improve the health of children and adults through research on the early development of cardiovascular disease, especially in the presence of ETS. Our aims are to: 1. Test the hypothesis that ETS induced vascular dysfunction in children is magnified in the presence of obesity. ETS-exposed and unexposed children ages 9-18 will be recruited. Children with normal BMI (<85% per age) and elevated BMI (>95% per age) will be studied in parallel. Forearm blood flow (FBF) will be determined by plethysmography as an assessment of endothelial performance in vivo. Vascular performance will be investigated in relation to vascular responses, blood lipids, inflammation markers, adiponectin, oxidative stress, and endothelial injury. 2. Test the hypothesis that circulating levels of endothelial progenitor cells (EPC) are predicted by ETS exposures in children and that obesity magnifies this effect. EPC counts will be determined in normal weight and obese youth and adolescents (both exposed and unexposed to ETS) by flow cytometry. EPC concentrations will be related to vascular responses, blood lipids, inflammation markers, adiponectin, oxidative stress, and endothelial injury. Relationships between degree and duration of ETS exposure and measured endpoints will be determined with covariate regression analyses and preliminary structural equation modeling. Defining the relationship and mechanisms of multi-risk factors (ETS and obesity) for cardiovascular disease in childhood as a result of this study will have significant implications for child and adult health. PUBLIC HEALTH RELEVANCE: The scientific links between environment tobacco smoke (ETS) and heart diseases, the number one killer in the country, in adults are well established. The relationship between ETS exposure and damage to the heart and blood vessels during childhood has not been studied. Meanwhile, childhood obesity has recently been described as the "new pandemic of the new millennium" and also has negative effects on heart health. The objective of this study is to define the relationship between ETS, obesity, and blood vessel function in children. A result of this study will have significant implications for child and adult health.