SICAS- Diversity Supplement

 描述(申请人提供)：哮喘是美国最常见的儿童慢性疾病，会导致严重的发病率，特别是在市中心，尽管采取了积极的措施来确定可补救的原因，但仍造成了数十亿美元的医疗保健利用。家庭环境是加剧症状的既定暴露来源，基于家庭的干预被证明是有效的。在学校内城市哮喘研究(SICAS-1)开始之前，还没有一项美国研究全面评估学校、教室和家庭环境中城市暴露与哮喘发病率之间的关系。几乎所有的小学生每天在学校的时间是7到12个小时，其中大部分时间是在一个教室里度过的。从SICAS-1中，我们了解到学生教室特定的老鼠过敏原、霉菌和颗粒污染物暴露与症状恶化有关。我们还展示了我们在繁忙的学校环境中减少这些暴露的能力。我们的建议建立在我们已建立的、成功的以学校为基础的基础设施上，以确定学校/课堂干预是否将通过减少这些暴露而有效和有效地改善哮喘发病率。我们的目标是确定以学校/教室为基础的环境干预在降低城市学龄儿童哮喘发病率方面的有效性。我们的中心假设是，减少教室/学校接触老鼠变应原、霉菌和颗粒物污染物将降低哮喘学生的哮喘发病率。我们计划对来自波士顿市中心40所小学多个教室的300名患有哮喘的小学生进行干预研究，以检验这一假设。我们的临床试验旨在确定以学校/教室为基础的环境干预措施(这些学校内的学校综合虫害管理和教室空气净化过滤器)的有效性，以减少哮喘发病率。我们的机械目的是验证一种假设，即基于学校/课堂的环境干预对哮喘症状/其他控制措施的影响是通过与呼吸道功能和哮喘相关的途径(其次是基因)中基因甲基化或表达的变化来实现的。这将扩大我们对哮喘免疫发病机制的理解，并为寻找哮喘治疗的潜在新靶点创造机会。在基因通路或网络中，我们将(A)确定我们的干预如何影响鼻呼吸道细胞甲基化或基因表达的变化；(B)评估我们干预相关的甲基化和基因表达变化如何影响哮喘预后；以及(C)通过中介分析估计干预在多大程度上是通过甲基化/基因表达变化来缓解哮喘症状。这项研究是一个史无前例的、影响巨大的机会，以测试我们是否可以有效地使学校环境中的儿童社区受益，而不是单身家庭中的个人。它还增加了一种关于健康结果的新的机械性应用。它有效地解决了一个严重的公共卫生问题，这个问题影响着越来越多的美国城市弱势儿童。

 DESCRIPTION (provided by applicant): Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization, despite aggressive measures to identif remediable causes. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are proven effective. Prior to the inception of the School Inner-City Asthma Study (SICAS-1), no American study had comprehensively evaluated the relationship between urban exposures in school, classroom, and home environments and asthma morbidity. Nearly all elementary school children spend 7 to 12 hours a day in school, and most of that time is spent in one classroom. From SICAS-1, we learned that student classroom-specific mouse allergen, mold, and particulate pollutant exposure is associated with worsening symptoms. We also demonstrated our ability to reduce these exposures in a busy, school setting. Our proposal builds upon our established, successful school-based infrastructure to determine whether a school/classroom intervention will efficiently and effectively improve asthma morbidity by reducing these exposures. Our goal is to determine the efficacy of school/classroom based environmental intervention in reducing asthma morbidity in urban schoolchildren. Our central hypothesis is that reducing classroom/school exposure to mouse allergen, mold, and particulate pollutants will decrease asthma morbidity in students with asthma. We plan to test this hypothesis in an intervention study of 300 elementary students with asthma from multiple classrooms in 40 Boston inner-city elementary schools. Our clinical trial aims are to determine the effectiveness of a school/classroom based environmental intervention (school integrated pest management and classroom air purifying filter units within these schools) to reduce asthma morbidity. Our mechanistic aim is to test the hypothesis that effects of school/classroom- based environmental interventions on symptoms/other measures of asthma control occur through changes in gene methylation or expression in pathways (and secondarily, in genes) relevant to airway function and asthma. This will expand our understanding of asthma immunopathogenesis and create opportunities to identify potential novel targets for asthma therapy. Within pathways or networks of genes we will (a) determine how our interventions influence changes in nasal airway cell methylation or gene expression; (b) evaluate how our intervention-associated changes in methylation and gene expression influence asthma outcomes; and (c) estimate through mediation analysis how much of the intervention effects on asthma symptoms occurs through methylation/gene expression changes. This study is an unprecedented, high impact opportunity to test whether we can efficiently benefit a community of children in the school environment as opposed to individuals in single homes. It also adds a novel mechanistic application on health outcomes. It efficiently tackles a critical public health problem that affects a growing proportion of disadvantaged, urban U.S. children.