Air Pollution, Salivary Extracellular Vesicles, and Asthma Severity in Children with Asthma

项目总结 哮喘恶化影响到一半以上被诊断为哮喘的儿童，并导致巨大的 经济负担。生活在城市地区的少数族裔哮喘儿童尤其受到急性哮喘的影响。 小插曲，导致缺课和学业成绩下降。研究一直以来都是 已确定的环境污染物，如颗粒物(PM)，是哮喘恶化的触发因素，但 确切的机制尚不清楚。表观遗传修饰，包括细胞外小泡(EV)和 它们被包裹的microRNA可能是PM诱导儿童哮喘发病的一个机制 被诊断出患有哮喘。缺乏能够识别早期不良反应的信息性但非侵入性生物标记物 暴露在高水平哮喘中的儿童的健康影响--触发污染物限制了有效的机会 预防和管理。为了解决这一差距，我的目标是在唾液中识别新的机械生物标记物， 一种现成的生物流体，可以反映环境暴露的影响，并可以识别儿童患上癌症的风险 哮喘加重。 我将利用哮喘中EVS的研究，以及它们在唾液中作为全身炎症标志物的作用。 唾液电动汽车(SEV)是一个新兴的令人兴奋的非侵入性诊断应用领域，对于大多数 血液中发现的化合物也存在于唾液中。此外，唾液中的各种成分(如电动汽车) 几乎可以反映正常和疾病状态的整个光谱。基于唾液的诊断较少 与目前相比，侵入性更低，成本更低，对患者和医疗保健提供者的风险更小 方法论。然而，到目前为止，还没有研究确定SEV作为一种生物标记物的潜力。 对PM暴露和哮喘加重的生物标志物的影响。 为了实现这一目标，我将进行一项研究，利用市中心学校独特的资源 哮喘研究，一项关于哮喘儿童的研究(n=300)，有唾液收集，广泛的暴露数据，以及 临床哮喘措施。每个受试者家外PM及其成分的浓度将为 使用先前验证的时空模型进行估计。我假设SEV编号和SEV- 封装的microRNA反映了最近(1-2天)环境PM暴露的水平(目标1，前瞻性分析) SEV数量及其包裹的microRNAs与儿童的发病率结果相关 哮喘(目标2，横断面分析)。我将进一步使用高级统计建模来集成SEV 暴露与哮喘加重之间的联系路径上的生物标志物(探索性目标3)。这项研究 解决了NIEHS的几个战略计划目标，包括：“识别和理解…生物通路…至 支持开发适用的预防…战略“(目标1)和”…理解不成比例的 疾病风险…“(目标6)。总之，这项研究将提供一种新的、非侵入性的工具来测量 这将有助于我们了解电动汽车在哮喘中所起的作用。

PROJECT SUMMARY Asthma exacerbations affect over half of children ever diagnosed with asthma and cause an immense economic burden. Minority children with asthma living in urban areas are particularly affected by acute asthma episodes, which result in missed school days and lowered academic achievement. Studies have consistently identified environmental pollutants, such as particulate matter (PM), as triggers of asthma exacerbations, yet the exact mechanisms are unclear. Epigenetic modifications, including changes in extracellular vesicles (EVs) and their encapsulated microRNA, may be a mechanism underlying PM-induced asthma morbidity in children diagnosed with asthma. The lack of informative yet non-invasive biomarkers that can identify early adverse health effects in children exposed to high levels of asthma-triggering pollutants curbs opportunities for effective prevention and management. To address this gap, my goal is to identify novel mechanistic biomarkers in saliva, a readily available biofluid, that reflect effects of environmental exposures and can identify children at risk for asthma exacerbations. I will leverage research on EVs in asthma and their roles in saliva as markers of systemic inflammation. Saliva EVs (sEVs) are an emerging and exciting field for noninvasive diagnostic applications, for a majority of compounds found in blood are also present in saliva. Moreover, the diverse components in saliva (such as EVs) can reflect virtually the entire spectrum of both normal and disease states. Saliva-based diagnostics are less invasive, less expensive, and present less risk to both the patient and health care provider than current methodologies. Yet to date, no studies have been conducted to identify the potential of sEVs as a biomarker of effect to PM exposure and biomarker of asthma exacerbations. To achieve this goal, I will conduct a study that leverages the unique resources of the School Inner-City Asthma Study, a study of children with asthma (n=300) that has saliva collection, extensive exposure data, and clinical asthma measures. Concentration of PM and its components outside each subject’s home will be estimated using a previously validated spatiotemporal model. I hypothesize that sEV number and sEV- encapsulated microRNAs reflect levels of recent (1-2 day) ambient PM exposure (Aim 1, prospective analysis) and that sEV number and their enclosed microRNAs are associated with morbidity outcomes among children with asthma (Aim 2, cross-sectional analysis). I will further use advanced statistical modeling to integrate sEV biomarkers on the paths linking exposure and asthma exacerbations (Exploratory Aim 3). This research addresses several NIEHS Strategic Plan goals including: “Identify and understand…biological pathways … to enable the development of applicable prevention … strategies” (Goal 1), and “…understand the disproportionate risks of disease…” (Goal 6). In conclusion, this research will provide a new, noninvasive tool to measure the burden of adverse air pollution exposures and will provide insight into the role of EVs in asthma.