Determinants of early childhood asthma and atopy following infant RSV infection

项目总结（见说明）： 项目1：RSV细支气管炎和幼儿哮喘分别是婴儿期和儿童期最常见、最严重、最急性和最慢性的疾病，也是给弱势群体造成不成比例负担的疾病。 机会和影响。该项目汇集了三个重要因素，以了解RSV在反复喘息和哮喘发病中的作用- RSV感染严重程度，宿主反应和易感性。 在研究RSV与哮喘发病的相关性时，研究主要集中在3-5%的RSV感染婴儿需要住院治疗，而绝大多数RSV感染是轻度的。轻度感染是否具有中等风险或具有保护作用是一个重要的问题。这个问题的答案将影响哮喘初级预防策略的建议。拟议的一系列调查将有助于我们了解RSV可能导致慢性肺部疾病的作用和机制，并可能防止慢性肺部疾病。 Approach.利用ReSPIRA队列（为本研究建立并在核心B中描述），我们将研究婴儿RSV感染、宿主对感染的反应以及RSV感染后复发性喘息、哮喘和过敏性疾病发展的遗传决定因素之间的关系。我们的具体目标是：（1）建立RSV LRTI、RSV URI/暴露和出生后前6个月内无RSV感染与复发性喘息和哮喘风险之间的关联，（2）确定婴儿RSV感染期间评估的宿主免疫应答和/或气道损伤生物标志物是否与复发性喘息、特应性疾病或早期儿童哮喘相关，（3）确定RSV感染后反复喘息、儿童早期哮喘和特应性表型的遗传决定因素。 该项目利用通过U19资助建立的ReSPIRA队列（包括2000名从婴儿早期到幼儿期的婴儿），将回答以下问题：（1）RSV如何引起哮喘，（2）婴儿期轻度RSV感染是否增加或减少哮喘的风险，以及（3）在婴儿RSV感染发展为儿童早期哮喘的过程中，哪些宿主因素是重要的。解决这些问题将使我们能够开发儿童慢性肺部疾病的预防干预措施，并最终改善美国和世界各地患有细支气管炎和哮喘的婴儿和儿童的健康。

PROJECT SUMMARY (See instructions): PROJECT 1: RSV bronchiolitis and early childhood asthma are the most common, serious, acute, and chronic conditions of infancy and childhood, respectively, and diseases that disproportionately burden vulnerable populations. Opportunity and Impact. This project draws together three important elements in understanding the role of RSV on recurrent wheezing and asthma inception - RSV infection severity, host response and susceptibility. In studying the association of RSV with asthma inception, studies have overwhelmingly focused on the 3-5% of RSV-infected infants requiring hospitalization, while the vast majority of RSV infections are mild. Whether mild infection confers intermediate risk or has a protective effect is an important question. The answer will influence proposals for primary asthma prevention strategies. The proposed series of investigations will aid in our understanding of the role and mechanisms through which RSV may both lead to chronic lung disease, and may protect from chronic lung disease. Approach. Utilizing the ReSPIRA cohort, established for this investigation and described in Core B, we will investigate the relationship between infant RSV infection, host response to infection, and genetic determinants of recurrent wheezing, asthma and allergic disease development following RSV infection. Our specific aims are to: (1) Establish the association between RSV LRTI, RSV URI/exposure, and no RSV infection in the first 6 months of life on the risk of recurrent wheezing and asthma, (2) Define whether host immune response and/or airway injury biomarkers assessed during infant RSV infection are associated with recurrent wheezing, atopic disease or early childhood asthma, and (3) Identify the genetic determinants of the phenotype of recurrent wheezing, early childhood asthma and atopy following infant RSV infection. Utilizing the ReSPIRA cohort which includes 2000 infants followed from early infancy through early childhood, and established through this U19 grant, this project will answer the following questions: (1) how does RSV cause asthma, (2) does mild RSV infection during infancy increase or decrease the risk of asthma, and (3) what host factors are important in the progression from infant RSV infection to early childhood asthma. Answering these questions will allow us to develop preventive interventions for chronic lung disease in children, and ultimately improve the health of infants and children with bronchiolitis and asthma in the U.S. and worldwide.