The school microbiome and asthma morbidity in inner-city children

项目概要/摘要 在理解如何定义和创造“健康”的室内微生物方面存在根本性的差距 为3亿儿童和成人哮喘患者提供良好的环境。越来越多的人认识到， 微生物组可能会影响哮喘的发展和发病率，但现有的环境微生物组很少， 对哮喘的研究表明，微生物暴露，如微生物多样性， 对预防哮喘和已诊断为哮喘的儿童的哮喘症状有害。很长的- 长期目标是为哮喘儿童创造健康的室内环境。本报告的总体目标 应用是调查教室微生物组对哮喘发病率的贡献， 我们是否可以改变室内微生物组，以减少哮喘症状， 学校内城哮喘干预（SICAS-2）研究，一项随机对照试验，由我们的 一组全面的学校为基础的综合虫害管理（IPM）干预结合 安慰剂对照教室高效微粒空气（HEPA）清洁剂干预，以评估 这些环境干预对哮喘发病率的影响。我们强大的初步数据支持中央 假设教室微生物组是可改变的，并且独立于过敏原影响哮喘发病率 通过殖民化暴露。我们将通过追求三个具体目标来检验中心假设：1） 确定教室微生物组在多大程度上可以通过随机IPM和HEPA清洁器进行修改 干预，可能与其他感染性和炎症性疾病相关的发现; 2）确定特定的 课堂微生物特征与哮喘症状独立相关，包括识别关节和 与过敏原暴露的相互作用效应，可能导致识别特定微生物菌株的发现 对未来的环境修复工作很重要; 3）通过以下方式估计上呼吸道定植的影响： 教室相关微生物对哮喘症状和宿主免疫状况的影响，这是一个重要的目标， 导致我们如何处理哮喘症状暴露缓解的范式转变，因为 人体微生物组可能在停止接触后继续存在。这种方法是创新的，因为这项研究是在 学校设置与随机环境干预，一个强大的设计，为人类研究， 进行因果解释。测试的假设偏离了现状，现状主要集中在 过敏原和微生物毒素。这项拟议中的研究意义重大，因为哮喘 影响了美国8.4%的儿童，也是造成学校旷课的主要原因。最终，这样的 知识有可能导致更好的未来预防和治疗策略，慢性肺 由于环境微生物暴露而引起的疾病。

PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding how to define and create a “healthy” indoor microbial environment for the 300 million children and adults with asthma. There is a growing recognition that the indoor microbiome may impact asthma development and morbidity, yet the few available environmental microbiome studies in asthma suggest that microbial exposures such as microbial diversity are simultaneously beneficial for asthma prevention and harmful for asthma symptoms in children already diagnosed with asthma. The long- term goal is to create healthy indoor environments for children with asthma. The overall objective of this application is to investigate the contribution of the classroom microbiome to asthma morbidity and determine whether we can modify the indoor microbiome to reduce asthma symptoms by leveraging the infrastructure of the School Inner-City Asthma Intervention (SICAS-2) study, a randomized controlled trial conducted by our group of a comprehensive school-based integrated pest management (IPM) intervention combined with a placebo-controlled classroom high efficiency particulate air (HEPA) cleaner intervention to assess the impact of these environmental interventions on asthma morbidity. Our strong preliminary data supports the central hypothesis that the classroom microbiome is modifiable and affects asthma morbidity independent of allergen exposure through colonization. We will test the central hypothesis by pursuing three specific aims: 1) To determine the extent to which the classroom microbiome is modifiable by a randomized IPM and HEPA cleaner intervention, findings that may be relevant for other infectious and inflammatory diseases; 2) Identify specific classroom microbial features independently associated with asthma symptoms, including identifying joint and interaction effects with allergen exposure, findings that may lead to identification of specific microbial strains important for future environmental remediation efforts; 3) Estimate the effect of upper airway colonization by classroom-associated microbes on asthma symptoms and the host immune profile, an important aim that may lead to a paradigm shift for how we approach exposure mitigation for asthma symptoms, since changes to the human microbiome may persist after exposure cessation. The approach is innovative, because the study is in the school setting with a randomized environmental intervention, a robust design for human studies that allows for causal interpretations. The hypothesis tested departs from the status quo, which is largely focused on allergens and microbial toxins in the home setting. The proposed research is significant, because asthma affects 8.4% of children in the United States and is the leading cause of school absenteeism. Ultimately, such knowledge has the potential to lead to better future prevention and treatment strategies for chronic lung disease due to environmental microbial exposures.