Symptom clusters in children with exacerbation-prone asthma

项目概要/摘要 在美国，哮喘症状控制在大多数儿童中是次优的，尽管广泛的 哮喘控制药物和标准化治疗指南的可用性。虽然哮喘死亡 每年有超过50%的哮喘儿童经历急性发作， 健康负担很重。虽然与哮喘症状控制相关的因素很复杂，但也 认识到有急性发作倾向的哮喘儿童是一个异质性群体，具有不同的症状， 可能导致不同临床结局的特征。然而，现有的哮喘症状研究， 这一年龄组是相当有限的，主要集中在孤立的呼吸道症状，忽视了其他 对整体功能状态很重要的身体症状和心理及社会健康症状 和生活质量。到目前为止，还没有尝试全面识别和表型症状， 集群（定义为独立于其他集群的两个或多个并发症状） 容易加重的哮喘鉴于这一主要缺点，这项为期48周的队列研究（N=173）将测试 总体假设，症状群及其相关的炎症和代谢途径 预测皮质类固醇治疗反应性（主要目标结局）和生活质量（患者报告 次要结果）在8-17岁有急性发作倾向的哮喘儿童中。具体目标是：（1）确定 和表型症状集群，并评估其时间轨迹，2）确定之间的关联 症状群和临床结果，以及3）识别潜在的炎症和代谢途径 有急性发作倾向的哮喘儿童的症状群。我们预计，一群患有 最差的身体，心理和社会健康症状将出现;我们进一步预计， 在这群儿童中的表现将随着时间的推移而稳定， 治疗反应性、最差的生活质量和最大程度的炎症。这个项目 涉及具有合作历史的多学科团队，并与NINR战略计划保持一致， 通过生物行为研究在慢性病中进行“先进症状科学研究”。预计 该项目的可交付成果包括：1）关于识别和临床效用的精确知识， 有急性发作倾向的哮喘儿童的症状群，2）确定潜在的机制 这些症状群可以在未来的干预性研究中作为目标。因为病情加重的孩子- 易发性哮喘很少报告单一症状，这些发现有可能显着推进 个体化治疗，改善临床结果，最终降低高发病率， 受影响儿童的生活质量。

PROJECT SUMMARY/ABSTRACT Asthma symptom control is suboptimal in the majority of children in the United States, despite widespread availability of asthma controller medications and standardized treatment guidelines. While deaths from asthma have declined, more than 50% of children with asthma experience an exacerbation each year and the public health burden is substantial. While the factors associated with asthma symptom control are complex, it is also recognized that children with exacerbation-prone asthma are a heterogeneous group, with differing symptom profiles that may contribute to differing clinical outcomes. However, existing research on asthma symptoms in this age group is quite limited and has focused primarily on respiratory symptoms in isolation, ignoring other physical symptoms and symptoms of mental and social health that are important to overall functional status and quality of life. To date, there has been no attempt to comprehensively identify and phenotype symptom clusters (defined as two or more concurrent symptoms independent of other clusters) in children with exacerbation-prone asthma. Given this major shortcoming, this 48-week cohort study (N=173) will test the overarching hypothesis that symptom clusters and their associated inflammatory and metabolic pathways predict corticosteroid treatment responsiveness (primary objective outcome) and quality of life (patient-reported secondary outcome) in children 8-17 years with exacerbation-prone asthma. Specific aims are to: 1) identify and phenotype symptom clusters and assess their temporal trajectories, 2) determine associations between symptom clusters and clinical outcomes, and 3) identify inflammatory and metabolic pathways underlying symptom clusters in children with exacerbation-prone asthma. We anticipate that a cluster of children with the poorest physical, mental and social health symptoms will emerge; we further anticipate that the symptom presentations in this cluster of children will be stable over time and will result in the poorest corticosteroid treatment responsiveness, the poorest quality of life, and the greatest magnitude of inflammation. This project involves a multidisciplinary team with a history of collaboration and is aligned with the NINR Strategic Plan to “Advance Symptom Science Research” in chronic conditions through biobehavioral research. Expected deliverables from this project include: 1) refined knowledge regarding the identification and clinical utility of symptom clusters in children with exacerbation-prone asthma, and 2) identification of mechanisms underlying symptom clusters that can be targeted in future interventional studies. Because children with exacerbation- prone asthma rarely report a single symptom, these discoveries have the potential to significantly advance individualized treatment and improve clinical outcomes, ultimately reducing the high morbidity and improving quality of life in affected children.