Vascular toxicities of environmental tobacco particulates in children

描述（由申请人提供）：环境烟草烟雾（ETS）和成人心血管疾病之间的联系已得到充分证实。许多形式的慢性心血管疾病是在儿童和/或成年早期开始的，在美国至少有四分之一的儿童暴露于ETS。除ETS外，儿童期超重和肥胖（影响约三分之一的儿科人群）是与成年期心血管疾病相关的重要独立风险因素。最近在成人和动物中的几项研究表明，肥胖是慢性全身性炎症的一种情况，导致代谢和心血管后果。尽管ETS、肥胖和炎症通常在儿童中共存，但它们的关系及其对成人疾病之前血管性能的影响尚未得到解决。我们的假设是，炎症，内皮功能障碍和氧化应激引起的ETS是加强肥胖和影响血管功能的儿童。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：1.检验ETS诱导的儿童血管功能障碍在肥胖存在下被放大的假设。将招募9-18岁的ETS暴露和未暴露儿童。将对BMI正常（每个年龄<85%）和BMI升高（每个年龄>95%）的儿童进行平行研究。前臂血流量（FBF）将通过体积描记法测定，作为体内内皮性能的评估。将研究血管性能与血管反应、血脂、炎症标志物、脂联素、氧化应激和内皮损伤的关系。2.检验以下假设：内皮祖细胞（EPC）的循环水平可通过儿童暴露于ETS来预测，而肥胖会放大这种影响。将通过流式细胞术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浓度将与血管反应、血脂、炎症标志物、脂联素、氧化应激和内皮损伤相关。ETS暴露的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建模来确定。作为这项研究的结果，确定儿童心血管疾病的多危险因素（ETS和肥胖）的关系和机制将对儿童和成人健康产生重大影响。公共卫生相关性：环境烟草烟雾（ETS）和心脏病之间的科学联系，在该国的头号杀手，在成年人中已经得到了很好的建立。儿童时期暴露于ETS与心脏和血管损伤之间的关系尚未得到研究。与此同时，儿童肥胖症最近被描述为“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.