The Cardiopulmonary Effects of Particulate Exposure

颗粒物暴露对心肺的影响

• 批准号: 7889425
• 负责人: David C Christiani
• 金额: $ 39.72万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7889425
• 关键词: Acute; Affect; Air; Air Pollution; Animal Model; Animals; Atherosclerosis; Biological; Biological Markers; Blood Pressure; Blood Vessels; Breathing; Burn injury; Caliber; Cardiac; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Cells; Cessation of life; Chromium; Chronic; DNA; DNA Methylation; Data; Environment; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Epigenetic Process; Epithelial; Exposure to; Fossil Fuels; Funding; Gene Expression; Genes; Genome; Goals; Health; Home environment; Hour; Human; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Response; Lead; Link; Logic; Lung; Lung diseases; Malignant neoplasm of lung; Manganese; Measurable; Measures; Mediating; Metals; Methods; Methylation; Mining; Modeling; Molecular; Molecular Profiling; National Research Council; Nickel; Nose; Occupational; Outcome; Oxidative Stress; Particulate; Particulate Matter; Pathway interactions; Physiologic pulse; Plasma; Plasma Proteins; Population; Population Study; Power Plants; Relative (related person); Research Priority; Resources; Respiratory Mucosa; Risk; Risk Factors; Source; Specific qualifier value; Staging; Structure of mucous membrane of nose; Surface; Technology; Testing; Tissues; Toxic effect; Transition Elements; Vanadium; Welding; arterial stiffness; base; cohort; data mining; genome-wide; heart rate variability; human subject; indexing; innovation; multidisciplinary; oxidative DNA damage; particle; particle exposure; peripheral blood; public health relevance; response; success; toxic metal; ultrafine particle

DESCRIPTION (provided by applicant): Epidemiological and animal studies have identified many potential mechanisms by which airborne particles may impact health. However, the relative importance of these potential pathways remains not well understood. Our competing renewal is a molecular epidemiologic study with the overall goal to investigate distinct biologic pathways that mediate the detrimental effects of exposure to particulate matter (PM), building upon our productive studies in this population during our last funding period. We have focused on particles from fossil fuel power plants and welding fume as a model to evaluate the health effects of metallic particles. We will test hypotheses regarding these exposures using three endpoints for hypothesis testing: 1) autonomic function, as measured by heart rate variability (HRV); 2) vascular function, as measured by blood pressure and arterial stiffness; and 3) epigenetic changes, measured by global methylation in DNA from peripheral blood and nasal mucosa brushings of exposed individuals. We will investigate potential PM mechanisms in a cohort of particle- exposed workers with well characterized exposure to PM2.5. We have shown that inhaled PM is associated with heart rate variability changes, and evidence of oxidative DNA damage, as well as systemic inflammation. Moreover, we have shown that metallic fume exposure produces systemic changes in gene expression in peripheral blood of exposed individuals. This cohort is advantageous because of the direct access to the environment in which to measure personal exposures directly and accurately and the high rate of participation and cooperation. To test our hypotheses, our first aim will assess how short-term (hours) exposure to particles (PM) affects cardiac autonomic function (as measured by changes in heart rate variability; HRV); and vascular function as measured by changes in blood pressure and arterial stiffness measured by Pulse Wave Analysis (PWA). Our second aim will assess whether long-term (years) PM exposure to metallic PM is associated with increased risk of impaired vascular function, and systemic inflammation. Our third aim will assess personal PM exposure in relation to epigenetic changes in peripheral blood and in nasal epithelial brushings, as measured by epigenome-wide DNA methylation. Our fourth aim is exploratory in which we will mine data mining from our existing gene expression results, and further assess the relationship between plasma profiles and the observed autonomic, vascular and inflammatory responses to PM. We will assess specific candidate biomarkers of early and chronic responses to metal-rich particulate exposures based on global gene expression profiles among this cohort. Our multidisciplinary team, combined with an established population, allows a unique opportunity to combine innovative methods with established epidemiologic methods for investigating particulate-associated cardiovascular and systemic effects in humans. PUBLIC HEALTH RELEVANCE: The mechanisms linking PM inhalation into the lung to adverse health outcomes, including cardiovascular diseases, have not been completely understood. In this study, we will investigate potential PM mechanisms in construction workers with well characterized exposure to PM with aerodynamic diameters <2.5 <m (PM2.5). We have focused on particles from fossil fuel power plants and welding as a model to evaluate the cardiovascular and systemic inflammatory health effects of metallic particles.

描述（由申请人提供）：流行病学和动物研究已经确定了许多潜在的机制，它们可能会影响健康。但是，这些潜在途径的相对重要性尚不清楚。我们的竞争更新是一项分子流行病学研究，其总体目的是研究不同的生物学途径，这些途径介导了暴露于颗粒物（PM）的有害影响，这是基于我们在上一个资金期间在该人群中的生产性研究。我们专注于化石燃料发电厂的颗粒和焊接烟雾，以评估金属颗粒的健康影响。我们将使用三个终点进行假设检验来检验有关这些暴露的假设：1）根据心率变异性（HRV）衡量的自主功能； 2）血压和动脉僵硬度测量的血管功能； 3）表观遗传变化，通过外周血和暴露个体的鼻粘膜刷子中的DNA中的全球甲基化测量。我们将研究粒子暴露的工人队列中的潜在PM机制，其表征良好，暴露于PM2.5。我们已经表明，吸入的PM与心率变异性变化以及氧化性DNA损伤的证据以及全身性炎症有关。此外，我们已经表明，金属烟雾暴露会在暴露个体的外周血中产生系统性变化。该队列是有利的，因为可以直接访问直接准确地衡量个人暴露的环境以及高度参与和合作的速度。为了检验我们的假设，我们的第一个目标将评估短期（小时）暴露于颗粒（PM）如何影响心脏自主神经功能（如心率变异性的变化衡量； HRV）；通过通过脉搏波分析（PWA）测量的血压和动脉刚度的变化来衡量的血管功能。我们的第二个目标将评估长期（年）PM暴露于金属PM是否与血管功能受损和全身性炎症的风险增加有关。我们的第三个目标将评估与周围血液的表观遗传变化和鼻上皮刷中的表观遗传变化有关的个人PM暴露，这是通过表观遗传组全依性DNA甲基化测量的。我们的第四个目标是探索性，我们将从现有的基因表达结果中挖掘数据挖掘，并进一步评估血浆谱与观察到的自主，血管和炎症反应对PM之间的关系。我们将根据该队列中的全球基因表达谱对早期和慢性反应的早期和慢性反应的特定候选生物标志物进行评估。我们的多学科团队与既定人群相结合，允许将创新方法与已建立的流行病学方法相结合，以研究与人类中颗粒相关的心血管和系统效应。 公共卫生相关性：将PM吸入到肺部与不良健康结果（包括心血管疾病）的机制尚未完全理解。在这项研究中，我们将研究具有良好表征的PM的潜在PM机制，其空气动力学直径<2.5 <m（PM2.5）。我们专注于化石燃料发电厂的颗粒和焊接作为评估金属颗粒的心血管和全身性炎症健康影响的模型。