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: 8300547
• 负责人: Roby Greenwald
• 金额: $ 12.22万
• 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/8300547
• 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; public health relevance; respiratory; response; responsible research conduct; student athlete; tool; toxicant; urban area

DESCRIPTION (provided by applicant) 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. Public Health Relevance: This proposed study will address the significant public health issue of increased air pollution exposure resulting from outdoor physical activity during periods of poor air quality. It will examine the role of intense physical activity on the relationship between air pollution and measured health outcomes, and it will provide information useful to assessing the balance between the benefits of outdoor exercise and the risks of air pollution exposure. The biomarker analysis portions of this study will also provide insight into the steps leading to the development of airway oxidative stress and the influence of various mixtures of air pollution oxidants.

描述（由申请人提供） 候选人 Roby Greenwald 博士的近期职业目标是检查吸入氧化剂的呼吸反应，特别是空气污染混合物对气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系公认的气道生物化学权威Lou Ann Brown博士的指导下进行，并由环境健康系著名分析化学家Dana Boyd博士和空气污染暴露评估方面的环境科学家Jeremy Sarnat博士共同指导。 Greenwald 博士的培训将包括报名参加临床研究理学硕士项目，以研究先进的流行病学和生物统计方法以及负责任的研究行为。 格林沃尔德博士还将报名参加生理学和生物化学课程，研究对吸入毒物的呼吸反应的分子和细胞力学，以及与呼吸和心血管系统有关的生理学课程。 Greenwald 博士将接受分析呼出的抗氧化剂和氧化还原生物标志物的实验室培训（与 Brown 博士一起）、使用高灵敏度色谱和质谱仪器发现和开发生物标志物的培训（与 Barr 博士一起）以及空气污染暴露评估方面的指导（Sarnat 博士）。 最后，培训部分将由流行病学顾问 Mitchel Klein 博士和身体活动分析顾问 Janet Fulton 博士提供支持。该奖项促进的培训将使候选人处于有利地位 实现他建立独立研究团队的长期职业目标，该团队将在理解空气污染健康影响机制和改善这一公共卫生风险方面取得突破。 候选人的制度环境非常支持拟议的活动。格林沃尔德博士所在的系有 9 名教职人员，主要研究方向是空气污染和公共卫生，该领域资金雄厚，包括美国环境保护署最近授予的五年期拨款，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设施，并在联合导师巴尔博士的指导下建立了最先进的分析化学设施。儿科导师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的研究人员。 该提案的研究部分将研究因暴露于空气污染混合物而造成的公共健康风险。这些风险已被流行病学调查反复认识到。尽管对确切作用机制的了解还不完整，但很明显，气道中氧化应激状态升高在观察到的健康影响中发挥着重要且可能的因果作用。同样，造成氧化损伤的空气污染的具体成分尚未完全确定，尽管有 可能是燃烧源颗粒物与气相氧化剂臭氧之间的协同作用。此外，与户外体育活动相关的空气污染剂量的增加具有重大的公共卫生意义。体育活动是对抗儿童和成人肥胖率上升的重要工具；然而，必须仔细考虑进行这种活动的地点和时间，以避免增加空气污染的公共卫生负担，并最大限度地发挥体育活动的积极作用。拟议的研究将通过测量环境中空气污染混合物的暴露情况以及由此产生的青少年急性健康后果和生物标志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进行体育活动期间环境空气污染物的浓度和成分。由于所选学校位于不同的当地环境中，一所位于人口稠密的城市地区，另一所位于树木繁茂的半乡村环境中，因此这些地点的学生接触颗粒物的程度不同。考生将在臭氧高、低季节进行空气质量采样，并在室内体育活动时进行采样作为参考。第二个目标是研究空气污染暴露与活跃青少年的急性呼吸反应之间的关系。 研究人员将使用非侵入性方法来评估肺功能和气道氧化应激的急性变化。在运动训练前后，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，用于分析氧化应激和脂质过氧化的标志物。由于与体力活动相关的通气率升高会导致环境氧化剂的吸入增加，因此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。第三个目标是检查暴露于城市空气污染后气道氧化应激的时间发展。他们将从足球队中招募参与者进行晨练，并每天进行 5 小时的后续监测。我们将每小时收集呼吸冷凝物样本，并分析它们的氧化过程标记，包括一些以前未在空气污染暴露背景下评估的标记。此外，我们将积极参与生物标志物的发现和评估过程。 公共卫生相关性：这项拟议的研究将解决贫困时期户外体育活动导致空气污染暴露增加的重大公共卫生问题 空气质量。它将研究剧烈的身体活动对空气污染和测量的健康结果之间关系的作用，并将提供有助于评估户外运动的好处和空气污染暴露风险之间的平衡的有用信息。这项研究的生物标志物分析部分还将深入了解导致气道氧化应激发展的步骤以及各种空气污染氧化剂混合物的影响。