Chronic outdoor air pollution, airway epithelial "omics" and asthma exacerbations in children

慢性室外空气污染、气道上皮“组学”和儿童哮喘恶化

基本信息

批准号：
10659167
负责人：
Franziska Rosser
金额：
$ 16.03万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659167
关键词：
Address Air Air Pollution Ancillary Study Asthma Behavior Therapy Behavioral Biological Markers Biological Specimen Banks Caring Cause of Death Child Child Care Child health care Childhood Asthma Chronic Clinical Clinical Management Clinical Trials Cross-Sectional Studies DNA Methylation Data Development Development Plans Disease Emergency Situation Environment Epidemiology Epigenetic Process Epithelium Evidence based intervention Exposure to Funding Gene Expression Genes Genomics Goals Government Health Personnel Hospitalization Individual Institution Intervention K-Series Research Career Programs Knowledge Lead Lung diseases Mentors Methods Methylation Modeling Nasal Epithelium Nose Nutritional Outcome Particulate Matter Pathogenesis Pilot Projects Play Policies Pollution Positioning Attribute Predisposition Preparation Proxy Puerto Rican Recommendation Research Risk Sampling Schools Statistical Data Interpretation Statistical Methods Susceptibility Gene Testing Therapeutic Time Tissue-Specific Gene Expression Tissues Training United States Environmental Protection Agency United States National Institutes of Health Visit Vitamin D Work airway epithelium ambient air pollution asthma exacerbation biomarker identification career development clinical care clinical practice cohort cost design differential expression epigenetic variation ethnic diversity fine particles genome-wide health care service utilization improved indexing insight methylation biomarker novel novel therapeutics pediatrician pollutant predictive marker predictive tools prevent randomized, clinical trials response risk prediction skill acquisition skills tool traffic-related air pollution transcriptomics

项目摘要

ABSTRACT: Outdoor air pollution is a known cause of childhood asthma exacerbations yet is rarely addressed in routine asthma care. This gap between scientific knowledge and clinical practice must be addressed to improve healthcare for children with asthma. While there is no ‘safe’ level of pollution, personal susceptibility to both air pollution and asthma exacerbations varies in children. Childhood asthma exacerbations are difficult to predict, lead to missed school and parental work days, and contribute substantially to healthcare utilization and costs. It is unclear if our current asthma therapies protect against pollution-induced exacerbations. Pollution reduction policies are the best intervention, yet until such time as ‘clean’ air is guaranteed for all, developing biomarkers identifying children at greatest risk of pollution-induced exacerbations are needed to develop interventions. The airway epithelium is an ideal tissue to study omics and develop new biomarkers of pollution-induced asthma exacerbations, as susceptibility genes for asthma are expressed in airway epithelium and pollutants (e.g. particulate matter <2.5𝜇m (PM2.5)) induce epigenetic and gene expression changes. Little is known about the effects of chronic pollution exposure on DNA methylation and gene expression in children with asthma, or whether such changes are associated with asthma exacerbations. Further, it is unknown if pollution avoidance recommendations (the Air Quality Index (AQI)) results in differential DNA methylation or gene expression. This proposal will: 1) determine the association between exposure to PM2.5 and residential proximity to a major road (a proxy for traffic-related air pollution) and (a) genome-wide DNA methylation and (b) gene expression in nasal (airway) epithelium from children with asthma; 2) identify differentially DNA methylated markers or expressed genes (by exposure level to PM2.5 or roadway) that are associated with asthma exacerbations; and 3) conduct an exploratory analysis to estimate the effects of the Environmental Protection Agency-sponsored AQI behavioral intervention on DNA methylation and gene expression from a trial of children with asthma. Aims 1- 2 uses existing data from two completed NIH-funded studies. Aim 3 uses banked biospecimens from a pilot randomized clinical trial of children receiving the AQI intervention on asthma action plans (i.e. clinical care). This proposal addresses an unmet need, namely developing ‘omic’ markers of pollutant-induced asthma exacerbations in children. Dr. Rosser’s career development plan provides for mastery of statistical genomic methods and analyses, and builds upon clinical trial management and analysis skills. She is well positioned for her proposed research given epidemiology background, skills with spatial modeling, and pilot data. This career development award will provide the skills and preliminary data for an R01 seeking to test whether epigenetic/gene markers predict risk of asthma outcomes and response to the AQI intervention.

抽象的：室外空气污染是儿童哮喘恶化的一个已知原因，但在日常工作中很少得到解决必须解决科学知识与临床实践之间的差距以改善哮喘护理。哮喘儿童的医疗保健虽然没有“安全”的污染水平，但个人对这两种空气的易感性。污染和儿童哮喘发作情况各不相同儿童期哮喘发作很难预测，导致缺课和缺课，并大大增加医疗保健利用率和成本。目前还不清楚我们目前的哮喘治疗是否可以防止污染引起的病情恶化。政策是最好的干预措施，但在保证所有人享有“清洁”空气之前，开发生物标记物需要确定最有可能因污染而病情恶化的儿童，以制定干预措施。气道上皮是研究组学和开发污染引起的新生物标志物的理想组织哮喘加重，因为哮喘易感基因在气道上皮和污染物中表达（例如颗粒物 <2.5𝜇m (PM2.5)）会引起表观遗传和基因表达变化，但人们对此知之甚少。慢性污染暴露对哮喘儿童 DNA 甲基化和基因表达的影响，或这些变化是否与哮喘恶化有关，此外，尚不清楚是否避免污染。建议（空气质量指数 (AQI)）会导致 DNA 甲基化或基因表达差异。该提案将： 1) 确定 PM2.5 暴露与住宅靠近主要道路之间的关联（与交通相关的空气污染的代表）和（a）全基因组 DNA 甲基化和（b）基因表达哮喘儿童的鼻（气道）上皮；2) 识别差异 DNA 甲基化标记或与哮喘恶化相关的表达基因（根据 PM2.5 或道路暴露水平）； 3) 进行探索性分析以估计环境保护局资助的影响一项针对哮喘儿童的试验对 DNA 甲基化和基因表达进行 AQI 行为干预。 1-2 使用 NIH 资助的两项已完成研究的现有数据，目标 3 使用来自试点的存储生物样本。对接受哮喘行动计划（即临床护理）AQI 干预的儿童进行的随机临床试验。该提案解决了一个未满足的需求，即开发污染物诱发哮喘的“组学”标记罗瑟博士的职业发展计划提供了对统计基因组学的掌握。她擅长方法和分析，并以临床试验管理和分析技能为基础。她提出的研究给出了流行病学背景、空间建模技能和试点数据。开发奖将为 R01 提供技能和初步数据，以测试是否表观遗传/基因标记可预测哮喘结果的风险以及对 AQI 干预的反应。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Persistent overweight or obesity, lung function, and asthma exacerbations in Puerto Rican youth.

DOI：
10.1016/j.anai.2022.01.004
发表时间：
2022-04
期刊：
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
影响因子：
0
作者：
Wong M;Han YY;Rosser F;Acosta-Pérez E;Canino G;Forno E;Celedón JC
通讯作者：
Celedón JC

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