Environmental Determinants of Asthma Exacerbation in Children

儿童哮喘恶化的环境决定因素

• 批准号: 10009467
• 负责人: ANDREW H LIU
• 金额: $ 20.75万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10009467
• 关键词: Adrenal Cortex Hormones; Affect; Allergens; Alternaria; Asthma; Bioinformatics; Biological; Biometry; Canis familiaris; Cessation of life; Child; Clinical; Clinical assessments; Collaborations; Diagnostic; Dictyoptera; Disease; Economic Burden; Economics; Emergency department visit; Endotoxins; Environment; Environmental Exposure; Estrogen receptor positive; Exhalation; Exposure to; Felis catus; Functional disorder; Genetic Transcription; Goals; Health Care Costs; Hospitalization; Human; Immune response; Individual; Infection prevention; Inflammatory Response; Knowledge; Lead; Low income; Lung; Measures; Mediating; Medical Care Costs; Methods; Minority; Molds; Mycotoxins; Nasal Epithelium; Nitric Oxide; Nitrogen Dioxide; Nose; Outcome; Ozone; Particulate Matter; Pathway interactions; Patients; Predisposition; Process; Public Health; Quality of life; Research Personnel; Rhinovirus; Rodent; Sampling; Schools; Science; Severities; Spirometry; Sputum; Symptoms; Techniques; Testing; Therapeutic Intervention; Tobacco smoke; Virus; Virus Diseases; Visit; Work; airway epithelium; airway inflammation; asthma exacerbation; environmental intervention; environmental tobacco smoke; eosinophil; health disparity; improved; inflammatory marker; insight; microbial; minimally invasive; molecular phenotype; novel strategies; peripheral blood; pollutant; premature; prevent; pyroglyphid; respiratory virus; response; synergism; urban children; urgent care

Asthma exacerbations are a public health problem that disproportionately affects urban and minority low-income children. Multiple factors contribute to poor asthma outcomes including 1) exposure to environmental asthma triggers that worsen symptoms and lead to exacerbations, and 2) viral infections. We hypothesize that respiratory viruses and multiple respirable environmental exposures both independently and interactively provoke airway epithelial and immune responses in children with asthma that lead to asthma exacerbations and exacerbation- related outcomes. To test this hypothesis, we propose the following aims: Aim 1: Investigate how individual and composite asthma-relevant environmental exposures (viruses, allergens, tobacco smoke, nitrogen dioxide, ozone, particulate matter, molds, endotoxin) contribute to asthma exacerbations and related outcomes (lung dysfunction, airway inflammation, severity, control) in urban children with exacerbation-prone asthma. Aim 2: Determine if individual and composite environmental exposures are associated with differences in airway epithelial and immune responses (bronchial and nasal) with Project 2, PI: Seibold. Aim 3: Determine which airway biological responses to environmental exposures mediate exposure-exacerbation relationships. Our proposal seeks to improve scientific knowledge about the environmental determinants of asthma exacerbations by seasonally measuring and tracking environmental exposures that are known to worsen asthma, and gaining insights to the mechanisms by which they exert their effects. As a result of the synergy with the other PPG components and Cores, we will be able to study the relationship of environment exposures to exacerbations and exacerbation-related outcomes (Clinical Core and Biostatistics, Bioinformatics and Environmental Sampling Core), and to respiratory viruses and airway responses (Project 2). By achieving the proposed aims, this knowledge will lead to a better understanding of exposure susceptibility, better prediction of exacerbations, and multiple targets for environmental and therapeutic interventions. Ultimately, the goal is to prevent asthma exacerbations, which could lead to lower healthcare costs, reduced health disparities, and better quality of life.

哮喘加重是一个公共卫生问题，对城市和居民的影响尤为严重 少数民族低收入儿童。多种因素导致哮喘结果不佳，包括 1) 暴露于环境哮喘会引发症状恶化并导致病情加重， 2）病毒感染。我们假设呼吸道病毒和多种呼吸道病毒 环境暴露既独立又交互地刺激气道上皮和 哮喘儿童的免疫反应导致哮喘恶化和恶化- 相关结果。为了检验这一假设，我们提出以下目标： 目标 1：调查个体和复合哮喘相关环境暴露的情况 （病毒、过敏原、烟草烟雾、二氧化氮、臭氧、颗粒物、霉菌、 内毒素）会导致哮喘恶化和相关结果（肺功能障碍、气道 城市儿童哮喘易恶化的炎症、严重程度、控制情况。 目标 2：确定个体和复合环境暴露是否与 项目 2、PI 的气道上皮和免疫反应（支气管和鼻腔）的差异： 塞博尔德。 目标 3：确定对环境暴露介导的气道生物反应 暴露-恶化关系。 我们的提案旨在提高有关环境决定因素的科学知识 通过季节性测量和跟踪环境暴露来预防哮喘恶化 已知会使哮喘恶化，并深入了解它们发挥作用的机制 影响。由于与其他 PPG 组件和核心的协同作用，我们将能够 研究环境暴露与恶化和恶化相关的关系 结果（临床核心和生物统计学、生物信息学和环境采样核心）， 以及呼吸道病毒和气道反应（项目 2）。通过实现拟议的目标， 这些知识将有助于更好地了解暴露敏感性，更好地预测 恶化以及环境和治疗干预的多个目标。最终， 目标是预防哮喘恶化，这可能会降低医疗费用， 减少健康差距，提高生活质量。