WTC Dust and Health: Effects of Coinciding High Acute and Subchronic PM Exposures

项目摘要/摘要 世界范围内环境颗粒物(PM)浓度的上升和高排放量的增加 沙尘暴或灾难性事件的暴露已将普通公众置于危险之中。在有研究的同时 研究与高浓度和低浓度PM暴露相关的健康影响，到目前为止，有 这不是一项同时检查这两种暴露的广泛研究。 最臭名昭著的大规模暴露之一发生在2001年9月11日。近3000人 在袭击中丧生，其中87%发生在纽约市(NYC)。13年后，人们在和 纽约市周围地区仍在遭受可能由灰尘和碎片暴露引起的疾病的折磨和死亡 从世贸中心(WTC)的倒塌中解脱出来。虽然一些疾病的病因是已知的，但由于 一系列独特的情况和令人困惑的影响，许多人的最终原因并非如此。已知的是什么 数十万人暴露在以WTC粉尘形式存在的高剂量PM中。这么高 然后，在剂量之后的几个月里，长期接触较低水平的WTC粉尘、削减的烟雾、柴油 废气和环境PM污染。 建议利用小鼠模型进行一项全面的体内暴露研究。一种中等敏感的野生动物 模式菌株FVB/NJ将在曝光中使用，以更好地区分群体，同时也产生 现实的炎症反应。风险敞口本身可以分为三大类：1) 高急性暴露(HAE)，2)HAE继之亚慢性暴露(SCE)，以及3)SCE。作为比较， HAE可使用WTC粉尘或浓缩环境颗粒物(CAPS)进行。姊妹会将是一个 更低浓度的WTC粉尘、帽子或柴油废气颗粒(DEP)。姐妹会将在一系列范围内进行 时间段(1-28天)，以便充分了解双重暴露的短期和长期影响。 三个主要暴露组将允许通过分离 组件。这种系统化的方法也将有助于确定串联曝光是否会产生 炎症不只是累加效应。此外，采集的组织样本还将用于 确定亚慢性暴露对WTC粉尘分布的影响。获取人体组织样本 将来自世界贸易中心卫生登记处的不同活体组织样本进行比较，以 确定金属分布、缔合和/或结构状态之间是否存在任何相关性 同步辐射光源。 总而言之，将调查与WTC粉尘暴露有关的慢性病的病因。这 事件也将被用作研究与亚慢性颗粒物相关的危害的案例研究 在一次重大的急性粒子暴露事件之后的暴露。小鼠体内暴露的平移模型 将与已公布的流行病学数据和可用的人体组织样本进行比较。

Project Summary/Abstract Rising worldwide ambient particulate matter (PM) concentrations and increasing occurrences of high volume exposures via dust storms or catastrophic events have put the general public at risk. While there are studies examining the health implications associated with high and low concentration PM exposures, to date there has not been an extensive study examining both exposures concomitantly. One of the most notorious large scale exposures occurred on September 11, 2001. Nearly 3,000 people perished in the attacks, 87% of which were in New York City (NYC) alone. Thirteen years later people in and around the NYC area are still suffering and dying from illnesses likely caused by dust and debris exposure from the collapse of the World Trade Center (WTC). While the etiologies of some illnesses are known, due to the unique set of circumstances and confounding effects, the definitive cause of many are not. What is known is that hundreds of thousands of people were exposed to a high dose of PM in the form of WTC dust. This high dose was then followed by months of chronic exposure to lower levels of WTC dust, cutting fumes, diesel exhaust, and ambient PM pollution. A comprehensive in vivo exposure study is proposed utilizing a mouse model. A moderately susceptible wild type strain, FVB/NJ, will be used in the exposures to better differentiate between groups while also generating realistic inflammatory responses. The exposures themselves can be broken down into three major groups: 1) high acute exposure (HAE), 2) HAE followed by subchronic exposures (SCE), and 3) SCE. For comparison, the HAE be performed with either WTC dust or concentrated ambient particles (CAPs). The SCE will be a lower concentration of WTC dust, CAPs, or diesel exhaust particles (DEP). The SCE will occur over a range of time periods (1 – 28 days) in order to fully understand the short and long term effects of the dual exposures. The three main exposure groups will allow for the origin of inflammation to be understood by isolating components. This systematic approach will also help determine if the tandem exposures generate inflammation beyond mere additive effects. Furthermore, harvested tissue samples will also be used to determine the effects of the subchronic exposures on WTC dust distribution. Human tissue samples obtained from the World Trade Center Health Registry will be compared with different in vivo tissue samples to determine if there are any correlations between metal distribution, associations, and/or structural states using a synchrotron light source. In summary, the etiologies of the chronic illnesses related to WTC dust exposure will be investigated. This incident will also be used as a case study examining the hazards associated with subchronic particle exposures following a major acute particle exposure event. A translational model of in vivo mouse exposures will be compared to published epidemiological data and available human tissue samples.