ULTRAFINE PARTICULATE MATTER & CARDIORESPIRATORY HEALTH

超细颗粒物

基本信息

批准号：
7606628
负责人：
RALPH J DELFINO
金额：
$ 0.12万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7606628
关键词：
Acute Address Admission activity Air Air Pollution Area Biochemical Biological Markers Blood Blood Pressure Caliber California Cardiac Cardiovascular Physiology Cardiovascular system Cause of Death Characteristics Clinical Computer Retrieval of Information on Scientific Projects Database Coronary heart disease County Deposition Elderly End Point Epidemiologic Studies Exhalation Exposure to Funding Goals Grant Health Heart Heart Diseases Hospital Mortality Hospitalization Hospitals Individual Inflammation Inflammatory Institution Knowledge Lead Life Literature Los Angeles Lung Measurement Measures Mediator of activation protein Morbidity - disease rate Nitric Oxide Oranges Outcome Oxidants Particulate Particulate Matter Physiological Population Populations at Risk Process Research Research Personnel Resources Risk Site Smog Source Thinking Thrombosis Ultrafine United States National Institutes of Health Vascular Endothelium aged airway inflammation biological adaptation to stress design mortality particle pollutant receptor respiratory ultrafine particle

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Heart disease is the leading cause of death and hospitalization among the elderly population, which makes the identification of preventable causes for heart disease morbidity and mortality a major goal of epidemiologic research. Numerous studies have shown associations of outdoor particulate matter (PM) air pollution with cardiovascular hospital admissions and mortality. However, the causal pollutant components and physiologic mechanisms for these associations are not fully understood. There is evidence that airway inflammation resulting from airway deposition of ultrafine particles (defined herein as < 0.18 m in diameter) could lead to an increase in thrombogenic and inflammatory activity in the blood, and to a disturbance in cardiovascular function. This is believed to result from oxidant stress responses at extra-pulmonary sites, including the vascular endothelium of the heart. Changes in intermediary endpoints such as inflammatory mediators are expected to increase the risk of adverse cardiovascular outcomes, particularly in people with underlying coronary heart disease (CHD). We propose to conduct a panel study with repeated measurements to evaluate acute cardiovascular and respiratory health effects of ultrafine PM personal, indoor and outdoor exposures. Over seven month periods, we will follow 72 nonsmoking elderly individuals with CHD living in areas with high air pollution levels in the Los Angeles Air Basin of California. We will study two regions of southern California with differing air pollution profiles: areas of Los Angeles County and North Orange County (pollutant emissions source sites with freshly emitted PM) and more inland areas of Eastern Los Angeles County, San Bernardino and Riverside Counties (down-wind smog receptor sites with aged PM). This will enhance variability in characteristics of ultrafine and accumulation mode particles, and enhance the external validity of findings to populations at risk. The design will maximize the utility of intensive exposure assessments by measuring multiple interrelated clinical, physiological and biochemical outcomes. The specific aims will address the following hypotheses: 1) Exposure to ultrafine particles will be associated with increased circulating biomarkers of inflammation and thrombosis, increased blood pressure, adverse cardiac clinical outcomes, and increases in a biomarker of airway inflammation, exhaled nitric oxide; and 2) These associations will be stronger for measurements of particle components and certain ambient sources thought to influence inflammatory processes through oxidant damage. We will also evaluate relationships of outcomes with accumulation mode PM (0.18-2.5 m) and coarse mode PM (2.5-10 m). We will assess whether estimates of association for predicted (adjusted) personal or indoor exposure to ultrafine or accumulation mode PM of outdoor origin are stronger than estimates of association for unadjusted (raw) personal or indoor exposures. Results of this study will advance knowledge on the cardiovascular and respiratory effects of ultrafine particles. Our results are expected to clarify findings in the literature of associations between ambient particulate air pollution (PM10 and PM2.5) and severe cardiovascular outcomes, including mortality and hospital admissions.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。心脏病是老年人群死亡和住院的主要原因，这使得确定心脏病发病率和死亡率的可预防原因成为流行病学研究的主要目标。大量研究表明室外颗粒物 (PM) 空气污染与心血管疾病住院率和死亡率之间存在关联。然而，这些关联的致病污染物成分和生理机制尚未完全了解。有证据表明，超细颗粒（本文定义为直径< 0.18 m）气道沉积引起的气道炎症可能导致血液中血栓形成和炎症活动增加，并导致心血管功能紊乱。这被认为是由肺外部位（包括心脏血管内皮）的氧化应激反应引起的。炎症介质等中间终点的变化预计会增加不良心血管结局的风险，特别是对于患有潜在冠心病 (CHD) 的患者。我们建议开展一项重复测量的小组研究，以评估个人、室内和室外接触超细颗粒物对心血管和呼吸系统健康的急性影响。在七个月的时间里，我们将追踪居住在加利福尼亚州洛杉矶空气盆地空气污染严重地区的 72 名患有先天性心脏病的不吸烟老年人。我们将研究南加州两个空气污染状况不同的地区：洛杉矶县和北奥兰治县的地区（新排放 PM 的污染物排放源点）以及东洛杉矶县、圣贝纳迪诺县和河滨县的更多内陆地区（下降-风雾受体位点与老化PM)。这将增强超细颗粒和积累模式颗粒特征的变异性，并增强研究结果对高危人群的外部有效性。该设计将通过测量多种相互关联的临床、生理和生化结果，最大限度地提高强化暴露评估的效用。具体目标将解决以下假设： 1) 接触超细颗粒将与炎症和血栓形成的循环生物标志物增加、血压升高、不良心脏临床结果以及气道炎症生物标志物呼出一氧化氮的增加相关；和 2）对于颗粒成分和某些被认为通过氧化损伤影响炎症过程的环境来源的测量，这些关联会更强。我们还将评估结果与累积模式 PM (0.18-2.5 m) 和粗略模式 PM (2.5-10 m) 的关系。我们将评估预测（调整后）个人或室内暴露于室外来源的超细或累积模式 PM 的关联估计是否强于未调整（原始）个人或室内暴露的关联估计。这项研究的结果将增进人们对超细颗粒对心血管和呼吸系统影响的认识。我们的研究结果有望澄清文献中有关环境颗粒物空气污染（PM10 和 PM2.5）与严重心血管结局（包括死亡率和入院率）之间关联的发现。