Mentored patient-oriented research in preschool wheezing disorders

项目摘要/摘要 喘息是学龄前儿童中一种非常普遍的症状，众所周知，这种症状很难治疗。而当 与喘息相关的因素是复杂的，人们也认识到学龄前儿童是一种 异质性组，具有不同的症状特征，这可能有助于不同的临床结果和 疾病轨迹。然而，症状科学在学龄前儿童中非常有限，并集中在 主要是孤立地关注呼吸道症状，忽视其他身体症状和精神症状 照顾者的社会健康对整体功能状态和生活质量很重要。到目前为止，有 没有尝试识别或研究症状群(定义为两个或更多同时出现的症状 独立于其他群组)出现反复喘息的学龄前儿童。这款K24应用程序名为 “学龄前喘息障碍辅导病人研究”寻求五年支援 受保护的时间来扩大首席调查员的指导活动，促进她的职业发展和 为推动她在学龄前复发儿童症状聚集方面的研究提供动力 气喘吁吁。首席调查员建立了一个广泛的关于学龄前喘息的研究项目 拥有无与伦比的基础设施、资源和协作者的环境。职业发展目标是 确保首席调查员有足够的时间指导和以病人为中心的临床工作 研究活动。该奖项还将允许首席调查员继续她在统计方面的教育 方法和研究设计，分子生物学和精确医学，帮助她扩大以病人为导向 研究计划。这项培训还将促进干预措施的设计，以降低严重程度和 幼儿喘息的发生率。最重要的研究假设是症状群和 相关的炎症途径预测12-59个月龄儿童的临床结果 反复喘息。具体目标是确定症状群是否预测病情恶化(主要 结果)和生活质量(次要结果)，并利用下一代测序来确定 症状群潜在的途径及其轨迹。该项目解决了以下创新问题 症状科学，并可能导致识别个性化干预的新生物标记物。更大 了解潜在的发病症状也将有助于解决这一严重的公共卫生问题 (喘息)这影响了美国越来越多的儿童。

PROJECT SUMMARY/ABSTRACT Wheezing is a highly prevalent symptom among preschool children that is notoriously difficult to treat. While the factors associated with wheezing are complex, it is also recognized that preschool children are a heterogeneous group, with differing symptom profiles that may contribute to differing clinical outcomes and disease trajectories. However, symptom science is quite limited in preschool children and has focused primarily on respiratory symptoms in isolation, ignoring other physical symptoms and symptoms of mental and social health in caregivers that are important to overall functional status and quality of life. To date, there has been no attempt to identify or study symptom clusters (defined as two or more concurrent symptoms independent of other clusters) in preschool children with recurrent wheezing. This K24 application entitled “Mentored Patient-Oriented Research in Preschool Wheezing Disorders” seeks five years of support for protected time to expand the Principal Investigator’s mentoring activities, promote her career development and provide momentum to advance her research on symptom clustering in preschool children with recurrent wheezing. The Principal Investigator has built an extensive research program on preschool wheezing in an environment with unparalleled infrastructure, resources and collaborators. Career Development goals are to ensure that the Principal Investigator will be provided sufficient time for mentoring and patient-oriented clinical research activities. The award will also allow the Principal Investigator to further her education in statistical methods and study design, molecular biology, and precision medicine to help her expand her patient-oriented research program. This training will also facilitate the design of interventions to reduce the severity and incidence of wheezing in young children. The overarching research hypothesis is that symptom clusters and their associated inflammatory pathways predict clinical outcomes in preschool children age 12-59 months with recurrent wheezing. Specific aims are to determine whether symptom cluster predicts exacerbation (primary outcome) and quality of life (secondary outcome) and to utilize next-generation sequencing to identify pathways underlying symptom clusters and their trajectories. This project addresses innovative questions in symptom science and may result in identification of novel biomarkers for personalized intervention. Greater understanding of symptoms underlying morbidity will also help tackle a critical public health problem (wheezing) that affects a growing proportion of children in the United States.