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

项目总结 使用传统培养技术的先前研究的综合证据表明，早期生命 上呼吸道真菌定植与儿童哮喘的发生密切相关 和过敏性鼻炎，这是导致儿童发病率和医疗费用增加的主要原因 人口。然而，真菌培养很难进行，敏感性很差，而且不能提供 对呼吸道中的整个真菌进行全面评估。因此，不同的真菌群落 (即，真菌菌群)栖息在幼儿的上呼吸道，还没有得到充分的评估，而且 它们对重要的生物途径或儿科呼吸结局的影响在很大程度上是未知的。致信地址 这些知识上的空白，这项建议的主要目标是描述上呼吸道真菌生物群的特征 在儿童早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 以下具体目标：目标1：评估儿童早期上呼吸道真菌菌群模式 与反复喘息、过敏性鼻炎和儿童哮喘的发展有关。目标2：实现 检查儿童早期上呼吸道真菌菌群模式是否与儿童肺炎的发生有关 局部免疫反应。为了快速、高效、经济地实现这些具体目标， 我们将1)在一组患有鼻咽癌的健康儿童(n=361)中进行嵌套队列研究 作为正在进行的大规模人口调查的一部分而获得的临床结果的样本和详细评估 出生队列，专门设计来识别和了解早产儿的风险因素 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 为了我们先前对早期生命的上呼吸道微生物群的多项研究而聚集在一起，以及 我们机构用于人类微生物组研究的丰富资源，以及3)建立在正在进行的 该领域专家之间的合作。这项提议的结果可能会为未来的设计提供参考 旨在预防和减轻儿童哮喘和过敏性鼻炎负担的干预措施 通过操纵早期生命的上呼吸道微生物群落。

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.