Vascular toxicities of environmental tobacco particulates in children

环境烟草颗粒对儿童的血管毒性

• 批准号: 7740372
• 负责人: John Anthony Bauer
• 金额: $ 22.59万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2011-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740372
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Animals; Appearance; Arterial Injury; Blood Vessels; Blood flow; Cardiovascular Diseases; Cardiovascular system; Cell Count; Cellular biology; Cessation of life; Child; Child Nutrition; Child health care; Childhood; Chronic; Coronary Arteriosclerosis; Country; Development; Disease; Endothelial Cells; Environment; Environmental Tobacco Smoke; Equation; Flow Cytometry; Forearm; Functional disorder; Goals; Growth Factor; Health; Heart; Heart Diseases; Hemostatic function; Inflammation; Injury; Investigation; Label; Link; Lipids; Maintenance; Measures; Medical; Metabolic; Modeling; Obesity; Outpatients; Overweight; Oxidative Stress; PTPRC gene; Particulate; Patients; Pediatric Hospitals; Performance; Pilot Projects; Plasma; Plethysmography; Population; Population Research; Positioning Attribute; Prevalence; Primary Health Care; Public Health; Recruitment Activity; Regression Analysis; Research; Research Infrastructure; Risk Factors; Smoke; Statistical Data Interpretation; Stem cells; Stress; Testing; Time; Tobacco; Tobacco smoke; Toxic effect; United States; Weight; adiponectin; blood lipid; cell type; design; improved; in vivo; inflammatory marker; innovation; non-smoker; obesity in children; oxidation; pandemic disease; public health relevance; respiratory; response

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.

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充分证实。许多形式的慢性心血管疾病始于儿童期和/或青年期，美国至少四分之一的儿童接触过 ETS。除 ETS 外，儿童期超重和肥胖（影响约三分之一的儿科人群）是与成年后心血管疾病相关的重要独立危险因素。最近对成年人和动物的几项研究表明，肥胖是慢性全身炎症的一种情况，会导致代谢和心血管后果。尽管 ETS、肥胖和炎症在儿童中经常共存，但在成人疾病发生之前，它们之间的关系及其对血管性能的影响尚未得到解决。我们的假设是，肥胖会加剧 ETS 引起的炎症、内皮功能障碍和氧化应激，并影响儿童的血管功能。总体目标是通过研究心血管疾病的早期发展，特别是在存在 ETS 的情况下，改善儿童和成人的健康。我们的目标是： 1. 检验这样的假设：ETS 引起的儿童血管功能障碍在肥胖的情况下会被放大。将招募 9 至 18 岁的接触过 ETS 的和未接触过 ETS 的儿童。 BMI正常（每个年龄<85%）和BMI升高（每个年龄>95%）的儿童将被并行研究。前臂血流量（FBF）将通过体积描记法确定，作为体内内皮性能的评估。将研究与血管反应、血脂、炎症标志物、脂联素、氧化应激和内皮损伤相关的血管性能。 2. 检验以下假设：内皮祖细胞 (EPC) 的循环水平是通过儿童 ETS 暴露来预测的，并且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。 ETS 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建模来确定。这项研究的结果是确定儿童时期心血管疾病的多风险因素（ETS 和肥胖）的关系和机制，将对儿童和成人的健康产生重大影响。公共卫生相关性：环境烟草烟雾 (ETS) 与心脏病（美国成年人的头号杀手）之间的科学联系已得到充分证实。儿童时期接触 ETS 与心脏和血管损伤之间的关系尚未得到研究。与此同时，儿童肥胖最近被描述为“新千年的新流行病”，并且对心脏健康也产生负面影响。本研究的目的是明确儿童 ETS、肥胖和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。