Genetics/Air Pollution/Respiratory Effects in Children

遗传学/空气污染/儿童呼吸系统影响

• 批准号: 6660327
• 负责人: JOHN M PETERS
• 金额: $ 354.3万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-13 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6660327
• 关键词: air pollution; asthma; children; clinical research; gene environment interaction; human subject; longitudinal human study; pollution related respiratory disorder; respiratory disorder epidemiology

DESCRIPTION (provided by applicant): This Program Project proposal is submitted to request funding for 4 research Projects and 4 supporting Cores building on the Children?s Health Study, an ongoing cohort study of some 6,000 children from 12 communities in Southern California which has yielded a wealth of data on the chronic effects of air pollution, but the results leave open questions that need further attention. The 4 Projects address the question of whether the observed changes in pulmonary function persist to adulthood, involve studying asthma incidence with the goal of identifying environmental and host factors, examine the genetic variation in oxidative stress pathways that modulate response to air pollution, and develop new biostatistical methods. Core 1 provides field logistics and technical support for the data collection, Core 2 provides biostatistical and data management support, Core 3 obtains data needed for exposure assessment, and Core 4 provides the genotyping and sample storage capability. Combining the 4 Projects into one Program Project promotes the interdisciplinary activity required to tackle complex projects while creating efficiencies that take advantage of existing resources and cores. The major hypotheses are: (1) Oxidative stress is the main biological pathway by which air pollution leads to adverse respiratory effects. Specific pollutants that give rise to reactive oxygen species (ROS) will have the greatest effects and these effects will be modified by genes involved in xenobiotic metabolism, inflammatory oxidant production, antioxidant production, ROS metabolism, and detoxification of oxidation products. Dietary antioxidant intake and other lifestyle factors such as physical activity will also modify these effects. (2) Pollutants contributing to these long-term effects are combustion-related and the biggest contributor is derived from motor vehicle emissions, and that the contributions from diesel emissions and freshly emitted automobile emissions can be distinguished by measurements of relevant markers such as fine elemental carbon (EC) particles and carbon monoxide (CO) and by spatial modeling of traffic density. (3) The respiratory effects of air pollution are multifaceted and interrelated. Thus, air pollution has effects on pulmonary function, on chronic respiratory diseases such as asthma, and on the frequency of respiratory illnesses. (4) The effects of air pollution on lung function and respiratory disease are irreversible and lead to permanent deficits continuing into adulthood.

描述（由申请人提供）： 该计划项目建议提交给4个研究的请求资金 项目和4个支持儿童健康研究的支持核心 正在进行的队列研究来自南部12个社区的6,000名儿童 加利福尼亚州产生了有关空气慢性影响的大量数据 污染，但结果留下了需要进一步关注的开放问题。 这4个项目解决了观察到的变化的问题 肺功能持续到成年，涉及研究哮喘发病率 为了确定环境和宿主因素，请检查 调节对空气反应的氧化应激途径的遗传变异 污染，并开发新的生物统计学方法。核心1提供字段 核心2提供了物流和技术支持，Core 2提供 生物统计学和数据管理支持，Core 3获得了所需的数据 暴露评估，Core 4提供了基因分型和样品存储 能力。将4个项目结合到一个计划项目中促进 解决复杂项目所需的跨学科活动 利用现有资源和核心的效率。专业 假设是：（1）氧化应激是主要的生物学途径 空气污染导致不良呼吸作用。具体的污染物 产生活性氧（ROS）将具有最大的影响，并且 这些作用将通过涉及异生物代谢的基因来改变， 炎性氧化剂产生，抗氧化剂产生，ROS代谢和 氧化产物的解毒。饮食抗氧化剂摄入量和其他 体育锻炼等生活方式因素也会改变这些影响。 （2）导致这些长期影响的污染物与燃烧有关 最大的贡献者来自汽车的排放， 柴油排放和新鲜发射的汽车的贡献 可以通过测量相关标记（例如 细元素碳（EC）颗粒和一氧化碳（CO）和空间 交通密度的建模。 （3）空气污染的呼吸作用是 多方面和相互关联。因此，空气污染对肺部有影响 功能，在慢性呼吸道疾病（例如哮喘）上 呼吸道疾病。 （4）空气污染对肺功能的影响 呼吸道疾病是不可逆的，导致永久缺陷 继续成年。