Genetics/Air Pollution/Respiratory Effects in Children

描述（由申请人提供）： 本计划项目提案提交申请资助4项研究 项目和4个支持核心建设的儿童？的健康研究， 正在对来自南部非洲12个社区的约6 000名儿童进行队列研究， 加州已经获得了大量关于空气慢性效应的数据 污染，但结果留下了需要进一步关注的开放性问题。 这四个项目涉及的问题是， 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， 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方法。核心1提供场 Core 2为数据收集提供后勤和技术支持， 生物统计和数据管理支持，核心3获得所需的数据， 暴露评估，核心4提供基因分型和样本储存 能力。将四个项目合并为一个项目， 需要跨学科的活动，以解决复杂的项目，同时创建 利用现有资源和核心的效率。主要 假设：（1）氧化应激是主要的生物学途径， 空气污染会对呼吸系统造成不良影响。特定污染物， 产生活性氧（ROS）将产生最大的影响， 这些作用将被涉及异生物质代谢的基因改变， 炎性氧化剂产生、抗氧化剂产生、ROS代谢，以及 氧化产物的解毒。膳食抗氧化剂摄入量和其他 生活方式因素，如体育活动，也会改变这些影响。 (2)造成这些长期影响的污染物与燃烧有关 最大的贡献者来自机动车排放， 柴油机排放和新排放的汽车排放的贡献 可以通过测量相关标记来区分排放， 细元素碳（EC）颗粒和一氧化碳（CO）， 交通密度模型。(3)空气污染对呼吸系统的影响 多方面和相互关联。因此，空气污染对肺部有影响。 功能，对慢性呼吸道疾病，如哮喘，和对频率 呼吸道疾病。(4)空气污染对肺功能的影响 和呼吸道疾病是不可逆转的， 一直延续到成年。

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.