Establishing the role of the upper airway mycobiome on childhood respiratory outcomes

确定上呼吸道真菌群对儿童呼吸系统结局的作用

• 批准号: 10041554
• 负责人: Suman Ranjan Das
• 金额: $ 25.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041554
• 关键词: Address; Allergic Disease; Allergic rhinitis; Asthma; Bioinformatics; Biological; Biological Response Modifiers; Birth; Child; Childhood; Childhood Asthma; Chronic Disease; Clinical; Clinical assessments; Cohort Studies; Collaborations; Communities; Culture Techniques; Data; Development; Disease; Epidemiology; Future; Goals; Health Care Costs; Household; Human Microbiome; Immune response; Institution; Intervention; Knowledge; Laboratories; Life; Lung diseases; Measures; Methods; Modification; Morbidity - disease rate; Nursery Schools; Onset of illness; Outcome; Pathway interactions; Pattern; Population; Prevention strategy; Pulmonology; Recurrence; Research Personnel; Resources; Respiratory System; Risk; Risk Factors; Role; Sampling; Statistical Data Interpretation; Techniques; Testing; Translational Research; United States National Institutes of Health; Wheezing; Work; aged; bacterial community; bacteriome; base; bioinformatics pipeline; cohort; cost effective; design; early childhood; fungus; interest; microbial genomics; microbiome research; multidisciplinary; mycobiome; next generation sequencing; novel; population based; prevent; respiratory; respiratory colonization; respiratory microbiome; respiratory microbiota

PROJECT SUMMARY The aggregated evidence from prior studies using conventional-culture techniques suggests that early-life upper airway colonization with certain fungi is strongly associated with the development of childhood asthma and allergic rhinitis, which are leading causes of morbidity and increased health care costs in the pediatric population. However, fungal cultures are difficult to perform, have poor sensitivity, and do not provide a comprehensive assessment of the entire fungi in the respiratory tract. Thus, the diverse fungal communities (i.e., the mycobiome) inhabiting the upper airway of young children have not been adequately assessed and their effect on important biologic pathways or pediatric respiratory outcomes is largely unknown. To address these gaps in knowledge, the main goals of this proposal are to characterize the upper airway mycobiome during early childhood using next-generation sequencing techniques and to examine its association with common childhood respiratory illnesses and the local immune response. To achieve these goals, we propose the following specific aims: Aim 1: To assess whether early childhood upper airway mycobiome patterns are associated with the development of recurrent wheeze, allergic rhinitis, and childhood asthma. Aim 2: To examine whether early childhood upper airway mycobiome patterns are associated with the development of the local immune response. To accomplish these specific aims in a rapid, efficient, and cost-effective manner, we will 1) conduct a nested cohort study among a group of healthy children (n=361) with serial nasopharyngeal samples and detailed assessment of clinical outcomes obtained as part of an ongoing, large, population-based birth cohort that was specifically designed to identify and understand the early-life risk factors of the development of childhood respiratory diseases, 2) capitalize on the laboratory and bioinformatic pipelines we have assembled for our multiple prior studies of the early-life upper airway microbiome, as well as the abundant resources at our institution for human microbiome research, and 3) build upon an ongoing collaboration between experts in the field. The results of this proposal could inform the design of a future interventions aimed to prevent the inception and reduce the burden of childhood asthma and allergic rhinitis through the manipulation of the early-life upper airway microbial communities.

项目摘要 使用常规文化技术的先前研究的汇总证据表明，早期生活 带有某些真菌的上呼吸道定植与儿童哮喘的发展密切相关 和过敏性鼻炎，这是发病率的主要原因和小儿医疗保健成本的增加 人口。但是，真菌培养很难执行，敏感性差，并且不提供 全面评估呼吸道中的整个真菌。因此，多元化的真菌社区 （即Mycobiome）居住在幼儿的上呼吸道尚未得到充分评估，并且 它们对重要的生物学途径或小儿呼吸系统结果的影响在很大程度上尚不清楚。解决 这些知识的差距，该提案的主要目标是表征上呼吸道mycobiome 在幼儿期间，使用下一代测序技术，并检查其与 常见的儿童呼吸道疾病和局部免疫反应。为了实现这些目标，我们建议 以下具体目的：目标1：评估幼儿时期呼吸道上的mimcobiome模式是否是 与复发性喘息，过敏性鼻炎和儿童哮喘的发展有关。目标2：到 检查幼儿时期呼吸道上的mimcobiome模式是否与发展有关 局部免疫反应。以快速，高效且具有成本效益的方式实现这些特定目标 我们将1）在一组健康的儿童（n = 361）中进行嵌套队列研究 作为正在进行的大型，基于人群的一部分获得的临床结果的样本和详细评估 专门设计的出生队列，旨在识别和理解早期生活的危险因素 儿童期呼吸道疾病的发展，2）利用实验室和生物信息管道的利用 已经为我们对早期寿命上呼吸道微生物组的多次研究组装了 我们的人类微生物组研究机构的大量资源，3）建立在持续的基础上 该领域专家之间的合作。该提案的结果可以为未来的设计提供信息 旨在防止开始并减轻儿童哮喘和过敏性鼻炎的干预措施 通过操纵早期生命的上呼吸道微生物群落。