Symptom clusters in children with exacerbation-prone asthma

项目摘要/摘要 在美国的大多数儿童中，哮喘症状的控制并不理想，尽管普遍存在 哮喘控制药物和标准化治疗指南的可获得性。而死于哮喘的人 已经下降，超过50%的哮喘儿童每年都会恶化，公众 健康负担很大。虽然与哮喘症状控制相关的因素很复杂，但它也是 认识到易加重哮喘的儿童是一个具有不同症状的异质性群体 可能有助于不同临床结果的概况。然而，现有的关于哮喘症状的研究 这个年龄段的人相当有限，主要集中在孤立的呼吸道症状上，而忽略了其他 身体症状和精神和社会健康的症状，对整体功能状态很重要 和生活质量。到目前为止，还没有尝试全面地识别和表型症状 聚集性(定义为独立于其他聚集性的两种或两种以上并发症状) 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 主要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(主要目标结果)和生活质量(患者报告 8-17岁易加重哮喘儿童的第二结果)。具体目标是：1)确定 和表型症状群，并评估它们的时间轨迹，2)确定 症状群和临床结果，以及3)确定炎症和代谢途径 易加重哮喘儿童的症状群。我们预计，一群患有 最糟糕的身体、心理和社会健康症状将会出现；我们进一步预计这些症状 这群儿童的表现将随着时间的推移保持稳定，并将导致最差的皮质类固醇 治疗反应性、最差的生活质量和最严重的炎症。这个项目 涉及一个具有协作历史的多学科团队，并与NINR战略计划保持一致，以 通过生物行为研究推进慢性疾病的症状科学研究。预期 该项目的成果包括：1)关于识别和临床应用的精炼知识 易加重哮喘儿童的症状群，以及2)潜在机制的识别 未来干预性研究中可作为靶点的症状群。因为病情恶化的孩子- 易感哮喘很少报告单一症状，这些发现有可能显著提高 个体化治疗，提高临床疗效，最终降低高发病率，改善 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.