Multifactorial spatiotemporal analyses to evaluate environmental triggers and patient-level clinical characteristics of severe asthma exacerbations in children

多因素时空分析评估儿童严重哮喘急性发作的环境触发因素和患者水平的临床特征

基本信息

批准号：
9884782
负责人：
Benjamin Alan Goldstein
金额：
$ 12.08万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-04 至 2021-02-28
项目状态：
已结题

项目摘要

Asthma is a chronic heterogeneous airway disorder characterized by inflammation, mucus hypersecretion, airway hyperreactivity, and impaired airflow. Severe exacerbations of asthma occur frequently in children and require immediate use of systemic steroid therapy to prevent serious outcomes such as hospitalization or death. In addition to direct health risks, pediatric asthma exerts a substantial cost burden, as asthma exacerbations are a leading cause of emergency department visits, hospitalization, and missed school days. Multiple environmental factors are purported to play a role in asthma symptoms, including aeroallergens, pollutants, weather changes, and community viral outbreaks such as influenza. Additionally, asthma prevalence is greater in children of low socioeconomic status (SES) and in African-American and Hispanic/Latino children, suggesting both environmental and genetic effects on asthma incidence and severity. The existence of geographical asthma “hotspots” indicates that asthma prevalence and severity are influenced by place-based risks, including local air quality, built environment factors, access to health care providers, socioeconomic factors, culture, and behavior. To effectively prevent and treat pediatric asthma attacks, it is necessary to understand how patient-specific characteristics interact with environmental factors to render an individual susceptible to severe asthma exacerbations. Lacking sufficient power, previous studies have largely examined suspected asthma triggers in isolation; thus, there is a significant knowledge gap regarding how environmental factors interact with each other and with patient-level factors to promote severe asthma exacerbations in pediatric populations. We hypothesize that a longitudinal analysis of environmental exposures and patient-level factors will elucidate new multifactorial causes of severe asthma exacerbations. To elucidate the contributions and interactions of environmental and patient-level factors, we will apply machine learning approaches to a longitudinal (2007-2017) geocoded database of patient electronic health records detailing asthma-related health encounters and publicly available, overlapping spatiotemporal environmental data. Further, we will evaluate the interactions between person-level clinical factors, including obesity, history of premature birth/bronchopulmonary dysplasia, and atopy, to determine their effects on susceptibility to selected environmental triggers. These analyses will 1) provide an analysis of the relative contribution and interactions of environmental factors to pediatric asthma exacerbations, 2) identify geographic hotspots of asthma prevalence and severity, and 3) determine how person-level clinical factors influence susceptibility to different asthma triggers. Our findings will provide new insights into risk factors for severe asthma exacerbations, spur new studies into the biological mechanisms that underlie the interactions between human biology and the environment, inform preventive strategies and patient education efforts, and serve as a model that can be expanded to larger cohorts.

哮喘是一种慢性异质气道障碍，其特征是感染，粘液分泌，分泌性，气道高反应性和气流受损。哮喘的严重加剧经常发生在儿童中，需要立即使用全身立体疗法，以防止严重的住院或死亡等严重结果。除了直接的健康风险外，小儿哮喘还付出了巨大的成本伯恩，因为哮喘病情加剧急诊科的主要原因，住院和错过上学日。多个环境据称因素可以在哮喘症状中发挥作用，包括气盐，污染物，天气变化，以及社区病毒爆发，例如影响力。另外，低儿童的哮喘患病率更高社会经济地位（SES）以及非裔美国人和西班牙裔/拉丁裔儿童环境和遗传对哮喘入口和严重程度的影响。地理哮喘的存在 “热点”表明哮喘患病率和严重程度受到基于地方风险的影响，包括当地的空气质量，建立环境因素，获得医疗保健提供者，社会经济因素，文化和行为。为了有效预防和治疗小儿哮喘发作，有必要了解患者特定的特征与环境因素相互作用，使个人容易受到严重哮喘的影响恶化。缺乏足够的能力，以前的研究在很大程度上检查了可疑的哮喘触发因素隔离;因此，关于环境因素如何与每个相互作用存在很大的知识差距其他和患者水平的因素可促进小儿种群中严重哮喘加重。我们假设对环境暴露和患者水平因素的纵向分析将阐明新的严重哮喘加重的多因素原因。阐明环境和患者级别的因素，我们将在纵向上应用机器学习方法（2007-2017）患者电子健康记录的地理编码数据库详细介绍了与哮喘相关的健康遭遇和公开相关的健康记录可用的，重叠的时空环境数据。此外，我们将评估人级临床因素，包括肥胖，早产史/支气管肺发育不良和特应性，确定它们对选定环境触发器的易感性的影响。这些分析将为1）提供分析环境因素对小儿哮喘恶化的相对贡献和相互作用，2）确定哮喘患病率和严重程度的地理热点，3）确定人级临床因素如何影响对不同哮喘触发因素的敏感性。我们的发现将为风险因素提供新的见解严重的哮喘加剧，刺激了对相互作用的生物学机制的新研究在人类生物学和环境之间，为预防策略和患者教育工作提供信息，以及用作可以扩展到更大人群的模型。