Determinants of early childhood asthma and atopy following infant RSV infection

项目总结(见说明)： 项目1：呼吸道合胞病毒毛细支气管炎和儿童早期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，对脆弱人群造成不成比例的负担。 机遇和影响。该项目汇集了三个重要因素来理解呼吸道合胞病毒在反复喘息和哮喘发病中的作用--呼吸道合胞病毒感染的严重性、宿主反应和易感性。 在研究呼吸道合胞病毒与哮喘发病的关系时，研究压倒性地集中在需要住院的3-5%的呼吸道合胞病毒感染婴儿身上，而绝大多数呼吸道合胞病毒感染是轻微的。轻微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。答案将影响主要哮喘预防策略的建议。拟议的一系列研究将有助于我们了解RSV可能导致慢性肺部疾病的作用和机制，并可能预防慢性肺部疾病。 接近。利用为本次调查而建立并在核心B中描述的呼吸队列，我们将调查婴儿呼吸道合胞病毒感染、宿主对感染的反应以及呼吸道合胞病毒感染后反复喘息、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)建立呼吸道合胞病毒LRTI、呼吸道合胞病毒URI/暴露和出生后前6个月无呼吸道合胞病毒感染与反复喘息和哮喘风险之间的联系；(2)确定在婴儿呼吸道合胞病毒感染期间评估的宿主免疫反应和/或呼吸道损伤生物标志物是否与反复喘息、特应性疾病或儿童早期哮喘相关；以及(3)确定婴儿呼吸道合胞病毒感染后反复喘息、儿童早期哮喘和特应性过敏的表型的遗传决定因素。 通过这项U19资助建立的包括2000名婴儿的呼吸道队列将回答以下问题：(1)呼吸道合胞病毒是如何引起哮喘的，(2)婴儿期轻微的呼吸道合胞病毒感染是否增加或降低了哮喘的风险，以及(3)在婴儿呼吸道合胞病毒感染到儿童早期哮喘的过程中，哪些宿主因素很重要。回答这些问题将使我们能够开发针对儿童慢性肺部疾病的预防性干预措施，并最终改善美国和世界各地毛细支气管炎和哮喘儿童的健康。

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.