SICAS- Diversity Supplement

 描述（由申请人提供）：哮喘是美国儿童最常见的慢性疾病，导致显著的发病率，特别是在市中心，并占数十亿美元的卫生保健利用，尽管积极的措施，以确定可补救的原因。家庭环境是加剧症状的既定接触源，以家庭为基础的干预措施被证明是有效的。在学校内城哮喘研究（SICAS-1）开始之前，没有美国研究全面评估学校，教室和家庭环境中的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都要在学校里呆7到12个小时，而且大部分时间都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小鼠过敏原，霉菌和颗粒污染物暴露与症状恶化有关。我们还证明了我们在忙碌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建立的，成功的学校为基础的基础设施，以确定是否学校/课堂干预将有效地和有效地改善哮喘发病率，减少这些风险。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/学校暴露于小鼠过敏原，霉菌和颗粒污染物将降低哮喘学生的哮喘发病率。我们计划在波士顿市中心40所小学的多个教室的300名哮喘小学生的干预研究中验证这一假设。我们的临床试验的目的是确定学校/教室为基础的环境干预（学校综合害虫管理和教室空气净化过滤器单元在这些学校），以减少哮喘发病率的有效性。我们的机制性目的是检验以下假设：基于学校/教室的环境干预对哮喘控制的症状/其他指标的影响是通过改变与气道功能和哮喘相关的通路（其次是基因）中的基因甲基化或表达发生的。这将扩大我们对哮喘免疫发病机制的理解，并为识别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气道细胞甲基化或基因表达的变化;（B）评估我们的干预相关的甲基化和基因表达变化如何影响哮喘结局;（c）通过中介分析估计有多少干预对哮喘症状的影响是通过甲基化/基因表达变化发生的。这项研究是一个前所未有的，高影响力的机会，以测试我们是否可以有效地受益于一个社区的儿童在学校环境中，而不是个人在单一的家庭。它还增加了一个新的机制的健康结果的应用。它有效地解决了一个关键的公共卫生问题，该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.