The school microbiome and asthma morbidity in inner-city children

内城区儿童的学校微生物组和哮喘发病率

• 批准号: 10541838
• 负责人: Peggy Sue Lai
• 金额: $ 68.82万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541838
• 关键词: Absenteeism; Address; Adult; Affect; Air; Allergens; Allergic Disease; Asthma; Child; Childhood Asthma; Chronic lung disease; Communicable Diseases; DNA; Data; Development; Diagnosis; Disease; Dust; Environment; Environmental Impact; Exposure to; Future; Goals; Health; Home; Human; Human Microbiome; Immune; Immune System Diseases; Indoor environment; Inflammatory; Infrastructure; Intervention; Intervention Studies; Joints; Knowledge; Life; Literature; Measures; Mediating; Mediation; Methods; Microbe; Mission; Morbidity - disease rate; Nose; Parents; Particulate; Persons; Pilot Projects; Placebo Control; Play; Prevention strategy; Property; Public Health; Randomized; Randomized, Controlled Trials; Research; Role; Sampling; Schools; Severities; Shotguns; Source; Specimen; Statistical Models; Structure; Symptoms; Testing; Toxin; United States; United States National Institutes of Health; Work; air cleaner; asthma prevention; asthmatic; burden of illness; clinical practice; design; environmental intervention; high efficiency particulate air filter; indoor pollutant; inner city; innovation; intervention effect; metagenomic sequencing; microbial; microbial community; microbiome; microbiome research; nasal microbiome; prevent; professional atmosphere; remediation; respiratory colonization; treatment strategy

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.

项目摘要/摘要 了解如何定义和创建“健康”室内微生物存在根本的差距 3亿儿童和成人哮喘的环境。人们越来越认识到室内 微生物组可能会影响哮喘的发育和发病率，但是很少有可用的环境微生物组 哮喘的研究表明，微生物暴露（例如微生物多样性）只是有益的 预防哮喘和对已经诊断为哮喘的儿童的哮喘症状有害。长期 术语目标是为哮喘儿童创造健康的室内环境。总体目标 应用是研究教室微生物组对哮喘发病率的贡献并确定 我们是否可以通过利用基础设施来修改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，这是我们的一项随机对照试验 一组综合的基于学校的综合害虫管理（IPM）干预措施与 安慰剂控制的教室高效颗粒空气（HEPA）清洁措施，以评估 这些对哮喘发病率的环境干预措施。我们强大的初步数据支持中央 假设教室微生物组是可修改的，并且影响哮喘发病率独立于过敏原 通过定殖接触。我们将通过追求三个具体目标来检验中心假设：1） 确定教室微生物组通过随机IPM和HEPA清洁剂的修改程度 干预，可能与其他传染病和炎症性疾病有关的发现； 2）确定具体 教室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，可能导致特定微生物菌株的发现 对于未来的环境修复工作很重要； 3）通过 在哮喘症状和宿主免疫轮廓上与课堂相关的微生物，这是一个重要的目的 导致我们如何缓解哮喘症状的暴露范围的范式转变，因为 暴露停止后，人类微生物组可能会持续。这种方法是创新的，因为该研究已 带有随机环境干预的学校环境，这是对人类研究的强大设计，允许 用于因果解释。该假设检验了与现状的偏离，这在很大程度上集中于 在家庭环境中的过敏原和微生物毒素。拟议的研究很重要，因为哮喘 在美国影响8.4％的儿童，是学校缺勤的主要原因。最终，这样的 知识有可能导致改善慢性肺的预防和治疗策略 由于环境微生物暴露而引起的疾病。

项目成果

Indoor Microbial Exposures and Chronic Lung Disease: From Microbial Toxins to the Microbiome.

• DOI: 10.1016/j.ccm.2020.08.005
• 发表时间: 2020-12
• 期刊: Clinics in chest medicine
• 影响因子: 5.7
• 作者: Wolf M;Lai PS
• 通讯作者: Lai PS

Host DNA depletion on frozen human respiratory samples enables successful metagenomic sequencing for microbiome studies.

冷冻人体呼吸道样本中宿主 DNA 的去除能够成功进行微生物组研究的宏基因组测序。

• DOI: 10.21203/rs.3.rs-3638876/v1
• 发表时间: 2024
• 期刊: Research square
• 作者: Kim,Minsik;Parrish2nd,RaymondC;Shah,ViralS;Ross,Matthew;Cormier,Juwan;Baig,Aribah;Huang,Ching-Ying;Brenner,Laura;Neuringer,Isabel;Whiteson,Katrine;Harris,JKirk;Willis,AmyD;Lai,PeggyS
• 通讯作者: Lai,PeggyS