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

世贸中心粉尘与健康：同时发生高急性和亚慢性 PM 暴露的影响

• 批准号: 9178860
• 负责人: Andrea Dawn Harrington
• 金额: $ 9万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2017-01-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178860
• 关键词: Acute; Archives; Area; Automobile Driving; Awareness; Brain; Breathing; Cardiopulmonary; Case Study; Chemicals; Chemistry; Chronic; Chronic Disease; Control Animal; Data; Diesel Exhaust; Dose; Dust; Epidemiology; Epithelial; Etiology; Event; Exposure to; General Population; Goals; Harvest; Health; Heart; Individual; Infiltration; Inflammation; Inflammatory Response; Inhalation Exposure; Kidney; Left; Light; Liver; Long-Term Effects; Lung; Maps; Metals; Minerals; Modeling; Morphology; Mus; Nature; New York City; Oropharyngeal; Particle Size; Particulate; Particulate Matter; Pathogenesis; Phase; Pollution; Population; Publishing; Registries; Research; Respiratory physiology; Risk; Slice; Source; Structure; Structure of parenchyma of lung; Synchrotrons; Techniques; Testing; Time; Tissue Harvesting; Tissue Sample; Tissues; abstracting; acute toxicity; air filter; airway remodeling; alkalinity; ambient particle; base; chemical group; climate change; cohort; emergency service responder; hazard; human tissue; in vivo; in vivo Model; lymph nodes; mRNA Expression; member; mouse model; neutrophil; particle; particle exposure; protein expression

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.

项目摘要/摘要 全球环境颗粒物（PM）浓度和大量发生的增加 通过沙尘暴或灾难性事件的暴露使公众处于危险之中。虽然有研究 检查与高浓度和低浓度PM暴露相关的健康影响，迄今为止 并非一项广泛的研究，对这两种暴露均同时研究。 2001年9月11日发生的最臭名昭著的大规模暴露之一。 袭击丧生，其中87％仅在纽约市（纽约市）。十三年后，人们 纽约市附近仍在遭受灰尘和碎屑造成的疾病而遭受痛苦和死亡 来自世界贸易中心（WTC）的崩溃。尽管某些疾病的病因是已知的，但由于 独特的环境和混淆效果，许多人的明确原因不是。已知的 是成千上万的人以WTC粉尘的形式暴露于高剂量的PM。这个高 然后，剂量随后几个月的长期暴露于较低的WTC灰尘，切烟，柴油 排气和环境PM污染。 使用小鼠模型提出了全面的体内暴露研究。中等易感的野生 类型应变，FVB/NJ，将在暴露中使用，以更好地区分组，同时也生成 现实的炎症反应。暴露本身可以分为三个主要群体：1） 高急性暴露（HAE），2）HAE，然后进行亚慢性曝光（SCE）和3）。为了进行比较， 使用WTC粉尘或集中的环境颗粒（盖）进行HAE。 SCE将是 WTC灰尘，帽子或柴油排气颗粒的浓度较低（DEP）。 SCE将发生在 时间段（1 - 28天），以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隔离来理解炎症的起源 成分。这种系统的方法还将有助于确定串联暴露是否生成 炎症超出了添加效应。此外，收获的组织样品也将用于 确定亚基疫苗暴露对WTC粉尘分布的影响。获得的人体组织样品 将来自世界贸易中心卫生注册表与不同的体内组织样本进行比较 确定金属分布，关联和/或结构状态之间是否存在任何相关性 Synchrotron Light源。 总而言之，将研究与WTC粉尘暴露有关的慢性疾病的病因。这 事件还将用作研究与亚慢性粒子相关的危害的案例研究 发生重大急性颗粒暴露事件后的暴露。体内小鼠暴露的翻译模型 将与已发表的流行病学数据和可用的人体组织样本进行比较。