The influence of air pollution mixtures on biomarkers of airway oxidative stress

空气污染混合物对气道氧化应激生物标志物的影响

• 批准号: 8490381
• 负责人: Roby Greenwald
• 金额: $ 12.38万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490381
• 关键词: Acute; Address; Adolescent; Adult; African American; Air; Air Pollutants; Air Pollution; Analytical Chemistry; Antioxidants; Area; Athletic; Award; Biochemical Process; Biochemistry; Biological; Biological Markers; Biostatistical Methods; Breathing; Cardiovascular system; Child; Chromatography; Clinical Research; Coupled; Data; Development; Devices; Dose; Dose-Rate; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental air flow; Epidemiologic Methods; Epidemiology; Equilibrium; Evaluation; Exercise; Exhalation; Exposure to; Faculty; Female; Funding; Gases; Glutathione Disulfide; Goals; Grant; Health; Heart Rate; Hour; Injury; Investigation; Knowledge; Laboratories; Lead; Lipid Peroxidation; Malondialdehyde; Mass Spectrum Analysis; Master of Science; Measures; Mentors; Mentorship; Molecular; Monitor; Motion; Nitric Oxide; Outcome; Oxidants; Oxidation-Reduction; Oxidative Stress; Ozone; Participant; Particulate; Particulate Matter; Phase; Physical Education; Physical activity; Physiology; Play; Pollution; Positioning Attribute; Process; Public Health; Pulmonary function tests; Recruitment Activity; Reduced Glutathione; Research; Research Personnel; Respiratory Mechanics; Respiratory System; Respiratory physiology; Risk; Role; Rural; Sampling; Schedule; Schools; Scientist; Seasons; Site; Soccer; Source; Students; Time; Training; Training Activity; United States Environmental Protection Agency; Universities; Youth; airway inflammation; authority; career; experience; fighting; follow-up; high school; insight; instrumentation; laboratory facility; male; member; obesity in children; particle exposure; pediatric department; pollutant; programs; prospective; respiratory; response; responsible research conduct; student athlete; tool; toxicant; urban area

The immediate career goals of the candidate, Dr. Roby Greenwald, are to examine the respiratory response to inhaled oxidants, specifically, the influence of air pollution mixtures on markers of airway inflammation and oxidative stress. The training portion of this application will be critically important to achieve these goals. Training activities will be conducted under the mentorship of Dr. Lou Ann Brown of the Emory University Department of Pediatrics, a recognized authority on airway biochemistry, and the co-mentorships of Dr. Dana Boyd, a renowned analytical chemist in the Department of Environmental Health, and Dr. Jeremy Sarnat, an environmental scientist with expertise in air pollution exposure assessment. Dr. Greenwald's training will include enrollment in the Master of Science in Clinical research program for study of advanced epidemiological and biostatistical methods as well as the responsible conduct of research. Dr. Greenwald will also enroll in physiology and biochemistry courses examining the molecular and cellular mechanics of the respiratory response to inhaled toxicants and physiology courses pertaining to the respiratory and cardiovascular systems. Dr. Greenwald will receive laboratory training in the analysis of exhaled antioxidants and redox biomarkers (with Dr. Brown), training in biomarker discovery and development using high sensitivity chromatography and mass spectrometry instrumentation (with Dr. Barr), and guidance in air pollution exposure assessment (Dr. Sarnat). Finally, the training portion will be supported by epidemiology consultant Dr. Mitchel Klein and physical activity analysis consultant Dr. Janet Fulton. The training facilitated by this award will make the candidate well-positioned to achieve his long-term career goal of establishing an independent research team that will achieve breakthroughs in understanding the mechanisms of air pollution health effects and ameliorating this public health risk. The candidate's institutional environment is highly supportive of proposed activities. Dr. Greenwald's department has 9 faculty members with a primary research focus on air pollution and public health, and is well- funded in this area, including a recently awarded five-year grant from the U.S. Environmental Protection Agency for the establishment of the Emory/Georgia Tech Clean Air Research Center. The Department of Environmental Health has recently moved into a large new office and laboratory facility and has recently established state-of-the-art analytical chemistry facilities under the direction of the co-mentor, Dr. Barr. The mentor's facilities in the Department of Pediatrics are no less impressive and include high-sensitivity instrumentation for analysis of biological samples and a supportive research staff. The research portion of this proposal will examine the public health risks resulting from exposure to air pollution mixtures. These risks have been repeatedly recognized by epidemiological investigations. Although understanding of the precise mechanisms of action is incomplete, it is apparent that an elevated state of oxidative stress in the airways plays an important and possibly causal role in observed health effects. Similarly, the specific components of air pollution responsible for oxidant injury have not been completely identified, although there is likely a synergy between combustion-source particulate matter with the gas-phase oxidant ozone. Furthermore, the increased air pollution dose associated with outdoor physical activity is of substantial public health significance. Physical activity is a critical tool to fight the risingrate of obesity in children and adults; however, where and when this activity occurs must be carefully considered to avoid increasing the public health burden of air pollution and to maximize the positive effects of physical activity. The proposed study will address these knowledge gaps by measuring environmental exposure to air pollution mixtures and resulting acute health outcomes and biomarkers in adolescents. The first research objective is to characterize the concentration and composition of ambient air pollutants at 2 high schools in Atlanta during time periods when students are engaged in physical activities. Since the selected schools are in different local environments with one in a dense urban area and the other in a wooded, semi-rural setting, students at these sites have different levels of particle exposure. The candidate will conduct air quality sampling during seasons of both high and low ozone and will also conduct sampling during indoor physical activities as a reference. The second objective is to examine the relationship between air pollution exposures and acute respiratory response in active adolescents. The investigators will use non-invasive approaches to assess acute changes in lung function and airway oxidative stress. Before and after athletic practice sessions, they will conduct pulmonary function tests, measure exhaled nitric oxide, and collect samples of exhaled breath condensate for analysis of markers of oxidative stress and lipid peroxidation. Since the elevated ventilation rate associated with physical activity leads to increased inhalation of ambient oxidants, the investigatorswill monitor activity intensity using a wearable device that contains a motion-sensing accelerometer and heart rate monitor. The third objective is to examine the temporal development of airway oxidative stress following exposure to urban air pollution. They will recruit participants from soccer teams that conduct morning practices and perform 5 hours of follow-up monitoring each day. We will collect breath condensate samples at hourly time-points and analyze them for markers of oxidative processes, including several not previously assessed in the context of air pollution exposure. In addition, we will actively engage in a process of biomarker discovery and evaluation.

候选人罗比·格林沃尔德博士的直接职业目标是研究吸入氧化剂后的呼吸反应，特别是空气污染混合物对呼吸道炎症和氧化应激标志物的影响。该应用程序的培训部分对于实现这些目标至关重要。培训活动将在埃默里大学儿科Lou Ann Brown博士的指导下进行，该博士是公认的呼吸道生物化学权威，并由环境卫生部著名分析化学家Dana Boyd博士和具有空气污染暴露评估专业知识的环境科学家Jeremy Sarnat博士共同指导。格林沃尔德博士的培训将包括注册临床研究理学硕士项目，学习先进的流行病学和生物统计学方法以及负责任的研究工作。格林沃尔德博士还将报名参加生理学和生化课程，研究吸入毒物引起的呼吸反应的分子和细胞学机制，以及与呼吸和心血管系统有关的生理学课程。格林沃尔德博士将接受分析呼出的抗氧化剂和氧化还原生物标记物的实验室培训(与布朗博士一起)，使用高灵敏度层析和质谱仪发现和开发生物标记物的培训(与巴尔博士一起)，以及空气污染暴露评估方面的指导(萨纳特博士)。最后，培训部分将由流行病学顾问Mitchel Klein博士和体力活动分析顾问Janet Fulton博士提供支持。由该奖项促成的培训将使候选人处于有利地位，以实现他的长期职业目标，即建立一个独立的研究团队，在了解空气污染对健康影响的机制和改善这种公共健康风险方面取得突破。 候选人的制度环境高度支持拟议的活动。格林沃尔德博士所在的系有9名教职员工，主要从事空气污染和公共健康方面的研究，并在该领域拥有充足的资金，包括美国环境保护局最近授予的一笔为期五年的拨款，用于建立埃默里/佐治亚理工学院清洁空气研究中心。环境卫生部最近搬进了一个大型的新办公室和实验室，并在共同导师巴尔博士的指导下，最近建立了最先进的分析化学设施。导师在儿科的设施同样令人印象深刻，包括用于分析生物样本的高灵敏度仪器和支持性研究人员。 这项提案的研究部分将审查暴露在空气污染混合物中所造成的公共健康风险。流行病学调查一再认识到这些风险。尽管对确切的作用机制的了解还不完全，但很明显，呼吸道氧化应激状态的升高在观察到的健康影响中起着重要的、可能是因果关系的作用。同样，造成氧化剂伤害的空气污染的具体成分尚未完全确定，尽管燃烧源颗粒物与气相氧化剂臭氧之间可能存在协同作用。此外，与户外体育活动相关的空气污染剂量增加对公共卫生具有重大意义。体育活动是抗击儿童和成人肥胖率上升的关键工具；然而，必须仔细考虑何时何地进行体育活动，以避免增加空气污染造成的公共健康负担，并最大限度地发挥体育活动的积极影响。拟议的研究将通过测量环境暴露于空气污染混合物以及由此导致的青少年急性健康后果和生物标记物来解决这些知识差距。第一个研究目标是描述亚特兰大两所高中学生从事体育活动期间环境空气污染物的浓度和组成。由于选定的学校位于不同的当地环境中，一所在人口稠密的城市地区，另一所在树木繁茂的半乡村环境中，这些地点的学生接触颗粒物的水平不同。候选人将在臭氧高和低的季节进行空气质量采样，并在室内体育活动期间进行采样作为参考。第二个目标是研究活跃青少年暴露于空气污染与急性呼吸道反应之间的关系。研究人员将使用非侵入性方法来评估肺功能和呼吸道氧化应激的急性变化。在运动训练之前和之后，他们将进行肺功能测试，测量呼出的一氧化氮，并收集呼出的呼吸冷凝物样本，以分析氧化应激和脂质过氧化的标志。由于与身体活动相关的通气率增加会导致环境氧化剂吸入增加，研究人员将使用包含运动感应加速度计和心率监测器的可穿戴设备来监测活动强度。第三个目标是研究暴露于城市空气污染后呼吸道氧化应激的时间发展。他们将从进行晨练的足球队招募参与者，并每天进行5小时的跟踪监测。我们将在每小时的时间点收集呼吸冷凝液样本，并分析它们的氧化过程标志，包括几个以前没有在空气污染暴露的情况下进行评估的标志。此外，我们还将积极参与生物标志物的发现和评估过程。