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

哮喘是一种慢性异质性气道疾病，其特征是炎症，粘液分泌过多， 气道高反应性和气流受损。哮喘的严重恶化经常发生在儿童中， 需要立即使用全身类固醇治疗，以防止严重后果，如住院或死亡。 除了直接的健康风险外，儿童哮喘还造成了巨大的成本负担，因为哮喘急性发作是 急诊室就诊、住院和缺课的主要原因。多重环境 据称在哮喘症状中起作用的因素包括空气过敏原、污染物、天气变化， 和社区病毒爆发，如流感。此外，哮喘患病率在低收入儿童中更高。 社会经济地位（SES）和非洲裔美国人和西班牙裔/拉丁裔儿童，这表明 环境和遗传对哮喘发病率和严重程度的影响。地理哮喘的存在 “热点”表明哮喘的流行和严重程度受到基于地点的风险的影响，包括当地的空气 质量，建筑环境因素，获得医疗保健提供者，社会经济因素，文化和行为。 为了有效地预防和治疗儿童哮喘发作，有必要了解如何针对患者的具体情况， 特征与环境因素相互作用，使个体易患严重哮喘 加重由于缺乏足够的力量，以前的研究主要研究了哮喘的可疑触发因素， 因此，在环境因素如何与每个人相互作用方面存在着巨大的知识差距。 其他和患者水平的因素，以促进严重哮喘急性发作的儿科人群。我们 假设环境暴露和患者水平因素的纵向分析将阐明新的 严重哮喘急性发作的多因素原因。阐明的贡献和相互作用 环境和患者水平的因素，我们将应用机器学习方法，以纵向（2007-2017） 详细描述哮喘相关健康遭遇的患者电子健康记录的地理编码数据库， 现有的重叠时空环境数据。此外，我们还将评估 个人水平的临床因素，包括肥胖、早产/支气管肺发育不良史和特应性， 以确定它们对选定环境触发物的易感性的影响。这些分析将1）提供一个 分析环境因素对儿童哮喘急性发作的相对影响和相互作用，2） 确定哮喘患病率和严重程度的地理热点，以及3）确定个人水平的临床因素 影响对不同哮喘诱因的易感性。我们的研究结果将提供新的见解的风险因素， 严重的哮喘恶化，刺激了对相互作用的生物学机制的新研究 人类生物学与环境之间的关系，为预防策略和患者教育工作提供信息， 作为一个模型，可以扩展到更大的群体。

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.