Early detection of adverse respiratory effects from air pollution

及早发现空气污染对呼吸道的不良影响

• 批准号: 9067413
• 负责人: Kiros T Berhane
• 金额: $ 47.24万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-05 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067413
• 关键词: 16 year old; Acute; Adverse effects; Air Pollutants; Air Pollution; Alveolar; Asthma; Bronchitis; California; Carbon; Characteristics; Child; Child health care; Chronic; Clinical; Cohort Studies; Complex Mixtures; DNA; DNA Sequence; Data; Development; Distal; Early Diagnosis; Epigenetic Process; Exhalation; Exposure to; Genetic; Genetic Variation; Growth; Growth and Development function; Health; Intervention; Joints; Lead; Life; Long-Term Effects; Lung; Measurement; Measures; Mediating; Mediation; Methods; Methylation; Modeling; Morbidity - disease rate; NOS2A gene; Nitric Oxide; Outcome Measure; Ozone; Particulate Matter; Population; Predisposition; Process; Protocols documentation; Public Health; Research; Respiratory physiology; Source; Symptoms; Variant; ambient air pollution; base; design; evidence base; follow-up; genetic variant; improved; innovation; mortality; new growth; pollutant; population based; premature; programs; promoter; prospective; respiratory; respiratory health; response; spatiotemporal; trafficking

DESCRIPTION (provided by applicant): Ambient air pollution at concentrations below the limits set by current regulatory standards is associated with significant adverse effects on children's respiratory health. A growing number of studies demonstrate that particulate matter (PM) and traffic-related near-roadway air pollutants (NRP) have substantial adverse health impacts, and that asthma and epigenetic or genetic sequence variants may increase susceptibility for air pollution-associated deficits in lung growth, bronchitis symptoms, and development and/or exacerbation of asthma. Intensive public health and regulatory interventions have reduced current levels of PM, ozone and NO2. It is unknown whether the reduced levels of the current ambient air pollution mixture are sufficient to protect children's health. Improved approaches for early detection of these chronic effects at the population level are needed to guide effective public health and regulatory interventions and to assure that children are fully protected from long-term adverse effects due to these air pollution exposures. One promising approach for population-based early detection is the use of exhaled nitric oxide (FeNO). FeNO50 is associated with acute adverse respiratory effects and is modulated by short-term acute changes in air pollution exposure. Furthermore, the proximal and distal airways may be focal points for adverse chronic effects of PM2.5, and NRP. We have developed new methods to characterize responses in the proximal and distal airway compartments using extended exhaled nitric oxide parameters [proximal bronchial wall flux (J'awNO), distal alveolar NO concentration (CANO)]. In this application, we propose to investigate the utility of FeNO for detecting the early effects of chronic exposures to air pollution, using data on long-term air pollution, FeNO, epigenetic and genetic variants in NOS2, and health outcomes measured longitudinally in the southern California Children's Health Study, an ongoing prospective population-based cohort study of environmental determinants of respiratory health in southern California children. Over 7 years of follow-up, which coincided with substantial reductions in levels of air pollution in southern California, we have collected more than 13,000 longitudinal measurements of FeNO50. We hypothesize that 1) FeNO50 and CANO can be used for early detection of chronic health effects from long-term exposure to PM2.5 and elemental carbon, EC2.5 (a measure of NRP); and 2) that early detection of chronic effects can be enhanced using epigenetic (DNA CpG methylation) and cis genetic sequence variants in NOS2 that are synergistically associated with both acute and chronic differences in FeNO50, J'awNO, CANO, and increased susceptibility to EC2.5 and PM2.5. The results from this program of research will fill crucial gaps in our ability to rapidly identify chronic effects of air pollution in the periodbefore irreversible adverse respiratory effects occur.

描述（由申请人提供）：环境空气污染浓度低于现行监管标准规定的限值时，会对儿童的呼吸系统健康产生重大不利影响。越来越多的研究表明，颗粒物（PM）和交通相关的近车道空气污染物（NRP）具有显著的不良健康影响，哮喘和表观遗传或遗传序列变异可能会增加对空气污染相关的肺生长缺陷，支气管炎症状以及哮喘发展和/或恶化的易感性。密集的公共卫生和监管干预措施降低了目前的PM、臭氧和NO2水平。目前尚不清楚目前环境空气污染混合物水平的降低是否足以保护儿童的健康。需要采取更好的办法，在人口一级及早发现这些慢性影响，以指导有效的公共卫生和监管干预措施，并确保儿童得到充分保护，免受这些空气污染暴露的长期不利影响。一个有希望的方法，以人口为基础的早期检测是使用呼出的一氧化氮（FeNO）。FeNO50与急性不良呼吸影响有关，并受到空气污染暴露的短期急性变化的调节。此外，近端和远端气道可能是PM2.5和NRP不良慢性效应的焦点。我们已经开发了新的方法来表征反应在近端和远端气道室使用扩展呼出一氧化氮参数[近端支气管壁流量（J'awNO），远端肺泡NO浓度（CANO）]。在这个应用程序中，我们建议调查的实用性FeNO检测慢性暴露于空气污染的早期影响，使用长期的空气污染，FeNO，表观遗传和NOS2的遗传变异的数据，和健康结果纵向测量在南加州儿童健康研究，一个正在进行的前瞻性人群为基础的队列研究，在南加州儿童呼吸健康的环境决定因素。经过7年的随访，恰逢加州南部空气污染水平大幅降低，我们收集了13，000多个FeNO50的纵向测量值。我们假设1）FeNO50和CANO可以用于早期检测长期暴露于PM2.5和元素碳的慢性健康影响，EC2.5（NRP的测量）;和2）使用表观遗传学可以增强慢性效应的早期检测（DNA CpG甲基化）和顺式基因序列变异与FeNO50的急性和慢性差异协同相关，J'awNO，CANO，并增加对EC2.5和PM2.5的敏感性。这项研究计划的结果将填补我们在不可逆转的不良呼吸影响发生之前快速识别空气污染慢性影响的能力的关键空白。