Genetics/Air Pollution/Respiratory Effects in Children

描述(由申请人提供)： 提交本计划项目建议书是为了申请4项研究的资金 关于儿童-S健康研究的项目和4个支持核心的建设 对南方12个社区约6,000名儿童正在进行的队列研究 加利福尼亚州，已经产生了大量关于空气慢性影响的数据 但结果留下了需要进一步关注的悬而未决的问题。 这4个项目解决的问题是观察到的变化是否 肺功能持续到成年，包括研究哮喘发病率 以确定环境和宿主因素为目标，检查 调节对空气反应的氧化应激途径的遗传变异 并开发新的生物统计方法。核心1提供字段 数据收集的后勤和技术支持，核心2提供 生物统计和数据管理支持，Core 3获得所需数据 暴露评估，核心4提供基因分型和样本存储 能力。将4个项目合并为一个计划项目可促进 在创建时处理复杂项目所需的跨学科活动 利用现有资源和核心的效率。少校 假设是：(1)氧化应激是主要的生物途径，通过 空气污染会导致不良的呼吸系统影响。特定的污染物 产生活性氧物种(ROS)将产生最大的影响和 这些效应将被参与异种新陈代谢的基因改变， 炎性氧化剂的产生、抗氧化剂的产生、ROS代谢和 氧化产物的脱毒。膳食抗氧化剂摄入量及其他 生活方式因素，如体力活动，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。 而最大的贡献者是机动车排放的废气， 柴油排放和汽车新排放的贡献率 排放可以通过测量相关的标志来区分，例如 细元素碳(EC)和一氧化碳(CO)及其空间分布 交通密度的建模。(3)空气污染对呼吸系统的影响包括 多方面的，相互关联的。因此，空气污染对肺脏有影响。 功能、对哮喘等慢性呼吸系统疾病和频率的影响 呼吸系统疾病。(4)空气污染对肺功能的影响 和呼吸道疾病是不可逆转的，会导致永久性的赤字 继续进入成年期。

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.