Midcareer Investigator Patient-oriented Research Award in Bronchiolitis & Asthma

职业生涯中期研究员毛细支气管炎患者导向研究奖

• 批准号: 8443115
• 负责人: Tina V Hartert
• 金额: $ 10.83万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443115
• 关键词: Address; Adult; Asthma; Award; Bronchiolitis; Child; Childhood; Childhood Asthma; Clinical; Development; Disease; Education; Environment; Environmental Risk Factor; Etiology; Extrinsic asthma; Funding; Genes; Grant; Human respiratory syncytial virus; Immune response; Infant; Infection; Integration Host Factors; Intervention Studies; Life; Lower Respiratory Tract Infection; Mentors; Midcareer Investigator Award in Patient-Oriented Research; Morbidity - disease rate; Natural History; Persons; Predisposition; Prevention; Prevention strategy; Primary Prevention; Recurrence; Research; Research Personnel; Research Project Grants; Resistance; Respiratory syncytial virus; Rhinovirus; Risk; Risk Factors; Role; Severities; Severity of illness; Time; Translating; Variant; Viral; Virus; Virus Diseases; Wheezing; asthma prevention; career; disease natural history; disorder prevention; experience; functional outcomes; infancy; interest; lung injury; meetings; patient oriented; patient oriented research; programs; public health relevance; respiratory

DESCRIPTION (provided by applicant): Asthma is the result of host and environment interactions. Lower respiratory tract infections (LRTI), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis not only experience significant morbidity, but are also at significantly increased risk for both recurrent wheezing and childhood asthma. We have established that respiratory syncytial viral infections appear to directly contribute to asthma causation, not just simply identify persons at risk for subsequent wheezing. Viral infections outside the infant period are also important, as they are modifiable environmental factors that have been established to be the most common cause of asthma exacerbations in both children and adults. This proposal uses a combined, parallel clinical and experimental approach to evaluate the contribution of, causality, and mechanisms through which respiratory syncytial virus, and human rhinovirus, contribute to asthma development and disease natural history. These studies all relate to the central hypothesis that viruses, as one significant environmental factor, alter the risk for developing asthma, as well as the natural history of prevalent disease. Specific testable questions related to this hypothesis include: 1) to determine the host factors among those with RSV and HRV infection that contribute to asthma development, 2) to determine the timing of infection during infancy and how that impacts the risk of developing childhood asthma; 3) to determine the mechanisms through which RSV and HRV contribute to asthma development, specifically focusing on lung injury and differential immune response to infection; 4) to determine if there are allelic variations in host genes involved with severity of respiratory viral infection that correlate with a predisposition or resistance to both infant bronchiolitis and childhood asthma; 5) to determine if there are allelic variation in RSV genes that are associated with both infant LRTI severity, and subsequent risk of asthma development.

描述（由申请人提供）：哮喘是宿主和环境相互作用的结果。由呼吸道合胞病毒（RSV）和鼻病毒（RV）等病毒引起的下呼吸道感染（LRTI）是婴儿毛细支气管炎的主要原因。婴儿 患有细支气管炎住院的患者不仅发病率很高，而且复发性喘息和儿童哮喘的风险也显着增加。我们已经确定呼吸道合胞病毒感染似乎直接导致哮喘的病因，而不仅仅是简单地识别出有随后喘息风险的人。婴儿期以外的病毒感染也很重要，因为它们是可改变的环境因素，已被确定为儿童和成人哮喘加重的最常见原因。该提案使用一种联合的、平行的临床和实验方法来评估呼吸道合胞病毒和人鼻病毒对哮喘发展和疾病自然史的贡献、因果关系和机制。这些研究都涉及到一个中心假设，即病毒作为一个重要的环境因素，改变了哮喘的发病风险，以及流行疾病的自然史。与该假设相关的具体可检验问题包括：1）确定RSV和HRV感染者中导致哮喘发展的宿主因素，2）确定婴儿期感染的时间以及如何影响儿童哮喘的风险; 3）确定RSV和HRV促进哮喘发展的机制，特别关注肺损伤和对感染的不同免疫反应; 4）确定在涉及呼吸道病毒感染严重性的宿主基因中是否存在等位基因变异，所述等位基因变异与婴儿细支气管炎和儿童哮喘的易感性或抗性相关; 5）确定RSV基因中是否存在与婴儿LRTI严重程度和随后的哮喘发展风险相关的等位基因变异。