Midcareer Investigator Patient-oriented Research Award in Bronchiolitis & Asthma

描述（由申请人提供）：近期目标：确定环境和遗传因素对毛细支气管炎和哮喘发生的作用，目的是设计和实施更有效的预防性治疗，以降低婴儿病毒感染和儿童哮喘的发生率和严重程度。 职业发展目标：为指导和研究活动提供足够的时间。 研究项目：哮喘被认为是宿主（遗传）和环境相互作用的结果。病毒 感染是一种重要的、可改变的环境因素，已确定其是儿童和成人哮喘恶化的重要原因;由病毒如呼吸道合胞病毒（RSV）和鼻病毒（RV）引起的下呼吸道感染（LRTI）是婴儿细支气管炎的主要原因。因毛细支气管炎住院的婴儿发生反复喘息和儿童哮喘的风险显著增加。目前尚不清楚病毒性呼吸道感染是否直接导致哮喘的病因，或者只是确定有随后喘息风险的人。因此，存在许多可能的决定因素，可能有助于毛细支气管炎的严重程度和随后的哮喘的发展。该提案使用了一种组合的、平行的临床和实验方法来评估病毒如何对哮喘病因和自然史做出贡献的贡献、因果关系和机制，所有这些都与病毒作为一种重要的环境因素改变哮喘发生风险以及流行疾病的自然史的中心假设有关。与这一假说相关的具体可检验问题包括：1）婴儿期呼吸道病毒病原体、环境因素和感染时间影响儿童哮喘的风险; 2）婴儿期下呼吸道病毒感染，该感染的严重程度与儿童哮喘风险增加相关; 3）与呼吸道病毒感染严重程度相关的基因的等位基因变异将与婴儿毛细支气管炎和儿童哮喘的易感性或抗性相关。 指导奖的目的将通过允许PI将其实验专业知识转化为指导儿童病毒性疾病和哮喘的进展和功能结局的临床研究来实现，下一个目标是从风险因素确定过渡到干预和疾病预防。

DESCRIPTION (provided by applicant): Immediate Goals: To determine the role of environmental and genetic factors on the development of both bronchiolitis and asthma, with the goal of designing and implementing more effective preventive therapies to reduce the incidence and severity of both infant viral infections and childhood asthma. Career Development Goals: To provide sufficient time for mentoring and research activities. Research Project: Asthma is thought to result from host (genetic) and environment interactions. Viral infections are one important, and modifiable environmental factor that have been established to be important causes of asthma exacerbations in both children and adults; 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 are at significantly increased risk for both recurrent wheezing and childhood asthma. It is not known whether viral respiratory infections directly contribute to asthma causation or simply identify persons at risk for subsequent wheezing. Thus, many possible determinants exist that may contribute to the severity of bronchiolitis and the subsequent development of asthma. This proposal uses a combined, parallel clinical and experimental approach to evaluate the contribution of, causality, and mechanism of how viruses contribute to asthma causation and natural history, all relating 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) the respiratory viral pathogen, environmental factors, and timing of infection during infancy impact the risk of developing childhood asthma; 2) lower respiratory viral infection during infancy, and the severity of that infection correlates with an increased risk of childhood asthma; 3) allelic variations at genes involved with severity of respiratory viral infection will correlate with a predisposition or resistance to both infant bronchiolitis and childhood asthma. The aims of the mentored award will be met by allowing the PI to translate her experimental expertise to direct clinical studies of progression and functional outcome of childhood viral illness and asthma, with the next goal to make the transition from risk factor determination to intervention and disease prevention.