Environmental Determinants of Asthma Exacerbation in Children

哮喘恶化是一个公共卫生问题，不成比例地影响城市和 少数低收入儿童。多种因素导致哮喘预后不良，包括1） 暴露于环境哮喘触发恶化症状并导致恶化， 和2）病毒感染。我们假设呼吸道病毒和多种可吸入病毒 环境暴露既独立又相互作用地引起气道上皮和 哮喘儿童的免疫反应导致哮喘加重和加重- 相关成果。为了验证这一假设，我们提出了以下目标： 目的1：调查个体和复合哮喘相关环境暴露如何影响 （病毒、过敏原、烟草烟雾、二氧化氮、臭氧、颗粒物、霉菌， 内毒素）导致哮喘恶化和相关结果（肺功能障碍、气道 炎症、严重程度、控制）。 目标2：确定个体和复合环境暴露是否与 气道上皮和免疫反应（支气管和鼻）与项目2的差异，PI： 赛博尔德 目的3：确定环境暴露介导的气道生物学反应 急性加重关系。 我们的建议旨在提高关于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， 众所周知，哮喘恶化，并获得深入了解他们发挥其作用的机制， 方面的影响.由于与其他PPG组件和核心的协同作用，我们将能够 研究环境暴露与急性加重和急性加重相关 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 急性加重，以及环境和治疗干预的多个目标。最后， 其目标是预防哮喘恶化，这可能导致更低的医疗费用， 减少健康差距，提高生活质量。

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.