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.

项目概要 先前使用传统培养技术进行的研究汇总的证据表明，生命早期 某些真菌的上呼吸道定植与儿童哮喘的发生密切相关 和过敏性鼻炎，这是儿科发病和医疗费用增加的主要原因 人口。然而，真菌培养很难进行，灵敏度差，并且不提供 对呼吸道内整个真菌的综合评估。因此，多样化的真菌群落 居住在幼儿上呼吸道的菌群（即菌群）尚未得到充分评估和 它们对重要生物途径或儿科呼吸结果的影响在很大程度上尚不清楚。致地址 由于知识上的差距，该提案的主要目标是描述上呼吸道真菌组的特征 在幼儿期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 目标 1：评估幼儿上呼吸道真菌组模式是否 与反复喘息、过敏性鼻炎和儿童哮喘的发生有关。目标 2： 检查儿童早期上呼吸道真菌组模式是否与以下疾病的发展相关： 局部免疫反应。为了以快速、高效和具有成本效益的方式实现这些具体目标， 我们将 1) 在一组患有连续鼻咽癌的健康儿童 (n=361) 中进行一项巢式队列研究 作为正在进行的、大规模的、基于人群的研究的一部分，获得了样本和对临床结果的详细评估 专门设计用于识别和了解婴儿早期生命危险因素的出生队列 儿童呼吸道疾病的发展，2）利用我们的实验室和生物信息管道 为我们之前对生命早期上呼吸道微生物组的多项研究以及 我们的机构拥有丰富的人类微生物组研究资源，并且 3）以持续的研究为基础 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 旨在预防儿童哮喘和过敏性鼻炎发生并减轻其负担的干预措施 通过操纵生命早期的上呼吸道微生物群落。