The role of platelet activation and particulate matter exposure in COPD morbidity

血小板活化和颗粒物暴露在慢性阻塞性肺病发病中的作用

基本信息

批准号：
9393069
负责人：
Ashraf Fawzy
金额：
$ 6.55万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9393069
关键词：
Air Air Pollution Attention Biological Markers Blood Platelets Blood Vessels CD40 Ligand Calcium Caliber Cardiovascular Diseases Cardiovascular system Cause of Death Chronic Obstructive Airway Disease Clinical Clinical Research Cohort Studies Comorbidity Coronary Arteriosclerosis Coronary artery Data Analyses Disease Disease Outcome Echocardiography Enrollment Environmental Exposure Exposure to Future Goals Heart Heart Diseases Home environment Individual Indoor Air Pollution Inflammation Intervention Investigation Link Lung Measurement Measures Mediator of activation protein Mentors Methods Morbidity - disease rate Mus National Institute of Environmental Health Sciences Outcome Outcome Measure Oxidative Stress P-Selectin Parents Participant Particulate Matter Pathway interactions Patients Phenotype Platelet Activation Platelet Count measurement Play Population Pulmonary artery structure Quality of life Reporting Research Research Personnel Respiratory Signs and Symptoms Respiratory physiology Risk Risk Factors Role Smoker Specificity Symptoms System Thromboxane B2 Time Training Visit Walking X-Ray Computed Tomography chest computed tomography clinical phenotype endothelial dysfunction environmental tobacco smoke exposure experience functional status high risk interest mortality multidisciplinary novel patient oriented pressure respiratory response skills therapeutic target

项目摘要

Project Summary/Abstract Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the US with cardiovascular (CV) disease representing a significant cause of morbidity and mortality. Exposure to air pollution represents a common risk factor for COPD and CV disease. People in the US spend the majority of their time indoors and our research group has shown that high indoor particulate matter (PM) concentrations are linked to worse COPD morbidity. Evidence suggests that platelet activation, long implicated in CV disease, may play a role in the pathophysiologic consequences of PM exposure. PM exposure has been associated with elevated markers of platelet activation in mice, healthy subjects and those with CV disease. Elevated markers of platelet activation have also been reported in patients with stable and exacerbated COPD. However, whether PM exposure is associated with increased platelet activation in patients with COPD, a population particularly at-risk for high air pollution exposures, and whether platelet activation plays a role in COPD morbidity remains unknown. We hypothesize that exposure to elevated indoor PM concentrations is associated with increased platelet activation and that platelet activation is associated with respiratory and CV morbidity among patients with COPD. To study the potential role of activated platelets in response to PM exposure and in COPD morbidity, we propose adding repeated measurement of markers of platelet activation in 100 former smokers with moderate-severe COPD enrolled in a study (CLEAN Air) to investigate the effect of an indoor air purifier intervention on COPD morbidity that includes intermediate CV outcomes as part of a sub- study (CLEAN Air Heart). This proposal has two novel aims. First, to determine the association between indoor PM concentrations and platelet activation among individuals with COPD, we will add measurement of three markers of platelet activation (11-dehydro-thromboxane B2, soluble P-selectin, and soluble CD40 ligand) at each of three visits (baseline, 3 and 6 months) while capitalizing on the quantification of environmental exposures and clinical phenotyping performed as part of the parent study. Second, to determine the association of platelet activation with respiratory morbidity and intermediate CV outcomes in patients with COPD, we will examine the association of the measured markers of platelet activation with respiratory outcomes such as lung function, symptoms, six-minute walk distance, and quality of life, and intermediate CV outcomes such as endothelial dysfunction, vascular stiffness and elevated pulmonary artery pressure. We will exploit the extensive characterization of participants' comorbidities in the parent studies while expanding CV phenotyping by newly measuring pulmonary artery diameter (to evaluate right heart strain) and coronary artery calcium (to quantify coronary artery disease). If we find that platelet activation is associated with PM exposure or COPD morbidity, future investigation of antiplatelet therapy as a potential therapeutic target in patients with COPD would be warranted.

项目概要/摘要慢性阻塞性肺疾病 (COPD) 是美国第三大死亡原因心血管（CV）疾病是发病率和死亡率的重要原因。暴露于空气中污染是慢性阻塞性肺病和心血管疾病的常见危险因素。美国人花费了大部分时间他们在室内的时间，我们的研究小组表明，室内颗粒物 (PM) 浓度较高与更严重的慢性阻塞性肺病发病率有关。有证据表明，长期以来与心血管疾病有关的血小板活化，可能在 PM 暴露的病理生理后果中发挥作用。 PM 暴露已关联小鼠、健康受试者和心血管疾病患者的血小板活化标志物升高。高架也有报道称，慢性阻塞性肺病稳定期和恶化期患者中存在血小板活化标志物。然而，PM 暴露是否与 COPD 患者血小板活化增加有关，暴露于高空气污染风险的人群，以及血小板活化是否在其中发挥作用 COPD 的发病率仍然未知。我们假设暴露于室内 PM 浓度升高与血小板活化增加有关，并且血小板活化与呼吸和心血管有关 COPD 患者的发病率。研究活化血小板对 PM 反应的潜在作用暴露和慢性阻塞性肺病发病率中，我们建议增加血小板活化标志物的重复测量 100 名患有中重度慢性阻塞性肺病的前吸烟者参加了一项研究 (CLEAN Air)，以调查以下效果：室内空气净化器对慢性阻塞性肺病（COPD）发病率的干预措施，包括作为子项目一部分的中间心血管结果研究（清洁空气心脏）。该提案有两个新颖的目标。首先，确定之间的关联慢性阻塞性肺病患者的室内 PM 浓度和血小板活化，我们将添加测量血小板活化的三种标志物（11-脱氢血栓烷 B2、可溶性 P-选择素和可溶性 CD40 配体）在 3 次访视（基线、3 个月和 6 个月）中的每一次进行，同时利用定量作为母研究的一部分进行的环境暴露和临床表型分析。其次，为了确定血小板活化与呼吸系统发病率和中间CV的关系对于慢性阻塞性肺病 (COPD) 患者的结果，我们将检查测量的血小板标记物的关联激活与呼吸结果有关，例如肺功能、症状、六分钟步行距离和呼吸质量生命和中间心血管结果，如内皮功能障碍、血管僵硬度和肺动脉高压动脉压。我们将利用参与者父母合并症的广泛特征研究同时通过新测量肺动脉直径（以评估正确的心脏应变）和冠状动脉钙（量化冠状动脉疾病）。如果我们发现血小板活化与 PM 暴露或 COPD 发病率相关，抗血小板治疗作为潜在的未来研究 COPD 患者的治疗目标是有必要的。