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

• 批准号: 10470284
• 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
• 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/10470284
• 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; DNA Methylation; Data; Development; Development Plans; Disease; Emergency Situation; Environment; Epidemiology; Epigenetic Process; Evidence based intervention; Exposure to; Funding; Gene Expression; Genes; Genomics; Goals; Government; Health Care Costs; Health Personnel; Hospitalization; Individual; 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; Randomized Clinical Trials; 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; care providers; career development; clinical care; clinical practice; cohort; design; differential expression; epigenetic variation; ethnic diversity; fine particles; genome-wide; health care service utilization; improved; indexing; insight; methylation biomarker; novel; novel therapeutics; pollutant; predictive marker; predictive tools; prevent; response; skill acquisition; skills; tool; traffic-related air pollution; transcriptomics

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.

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