Impact of Sleep Duration on Immune Balance in Urban Children with Asthma

项目概要/摘要 由于环境不利于睡眠和睡眠，城市患有哮喘的儿童睡眠不足的风险很高。 哮喘管理。此外，这一群体的免疫平衡发生了改变，这是一个关键的生物过程 导致哮喘发病率和睡眠健康的个体差异。过敏性哮喘是一种慢性病 主要由辅助 T 1 (Th1)/ 2 (Th2) 细胞因子平衡紊乱（以 Th2 为标志）驱动的炎症性疾病 细胞因子（IL-4、IL-5 和/或 IL-13）占优势。对健康成年人的实验结果表明，缩短 睡眠会增加炎症细胞因子（例如 IL-6）和某些 Th2 细胞因子水平，并且恢复睡眠 睡眠限制后可促进免疫平衡的恢复。睡眠时间是否起着关键作用 城市哮喘儿童的免疫功能和相关的哮喘活动仍然是一个科学空白。我们会 使用以睡眠时间为目标的实验设计，因为 (1) 城市环境和哮喘 症状相互作用会缩短睡眠，（2）睡眠持续时间是一种可改变的行为，在临床护理中被忽视 患有哮喘的城市儿童，以及（3）实验数据对于测试睡眠时间与睡眠时间之间的因果关系至关重要 免疫平衡和哮喘的潜在机制。 我们将招募患有持续性过敏性哮喘且睡眠充足的城市儿童（N=204；年龄8-9岁） 持续时间（9-11 小时），谁将完成为期 4 周的受试者内协议，其中包括 3 个预定的实验 睡眠条件：(1) 1 周稳定睡眠（个性化；9-11 小时卧床时间），(2) 1 周缩短睡眠 （卧床时间减少 1.5 小时），以及 (3) 2 周恢复性睡眠（卧床时间增加 1.5 小时）。我们将监控 每天测量睡眠时间（体动记录仪）和肺功能（家庭肺活量测定），并每周评估免疫生物标志物 以及在睡眠时间缩短的中点。为了控制研究时间效应，我们的 1/3 样本将仅接受 在整个 4 周的方案中稳定的睡眠时间表。在这个项目中，我们将只研究患有以下疾病的城市儿童： 获得充足睡眠的过敏性哮喘患者（9-11 小时，符合国家指南）。我们的缩短睡眠方案 将模拟城市哮喘儿童因哮喘和/或城市环境而经历的睡眠不足。 此外，我们的恢复睡眠方案模拟了睡眠时间缩短后的睡眠优化干预 以一种良好控制的方法。 该研究的首要目的是检查睡眠时间缩短对免疫平衡的影响[例如，Th1 （干扰素-IFNγ）/Th2（白介素-IL-4、IL-5、IL-13）R 和血浆 IL-6 水平]。第二个目标涉及 确定恢复睡眠对免疫平衡的影响。第三个目标涉及检查 免疫平衡的变化与哮喘相关肺功能的变化有关（ FEV1) 在缩短和恢复睡眠的情况下。这项研究的结果最终将支持 开发可行的、生态有效的、具有临床意义的干预措施来优化睡眠时间， 该高危人群的免疫平衡和哮喘。

Project Summary / Abstract Urban children with asthma are at high risk for short sleep, due to an environment that jeopardizes sleep and asthma management. Further, this group suffers from altered immune balance, a key biological process contributing to individual differences in asthma morbidity and sleep health. Allergic asthma is a chronic inflammatory disorder driven primarily by disturbed T helper 1 (Th1)/ 2 (Th2) cytokine balance marked by Th2 cytokine (IL-4, IL-5 and/or IL-13) predominance. Experimental findings in healthy adults show that shortened sleep increases inflammatory cytokine (e.g., IL-6) and certain Th2 cytokine levels and that recovery sleep following sleep restriction promotes a return to immune balance. Whether sleep duration plays a key role in immune function and associated asthma activity in urban children with asthma remains a scientific gap. We will use an experimental design that targets sleep duration, because (1) the urban environment and asthma symptoms interact to shorten sleep, (2) sleep duration is a modifiable behavior overlooked in clinical care of urban children with asthma, and (3) experimental data are critical to test a causal link for sleep duration as a mechanism underlying immune balance and asthma. We will enroll urban children (N=204; ages 8-9 years) with persistent allergic asthma and adequate sleep duration (9-11 h) who will complete a 4-week within-subjects protocol that includes 3 scheduled experimental sleep conditions: (1) 1 week stabilized sleep (individualized; 9-11 h time in bed), (2) 1 week shortened sleep (1.5 h decrease in time in bed), and (3) 2 weeks recovery sleep (1.5 h increase in time in bed). We will monitor sleep duration (actigraphy) and lung function (home spirometry) daily and assess immune biomarkers weekly and at the midpoint of shortened sleep. To control time-in-study effects, 1/3 of our sample will receive only the stabilized sleep schedule across the 4-week protocol. In this project, we will study only urban children with allergic asthma who obtain sufficient sleep (9-11 h, within national guidelines). Our shortened sleep protocol will model the sleep loss that urban children with asthma can experience due to asthma and/or urban context. Additionally, our recovery sleep protocol simulates a sleep optimization intervention following shortened sleep in a well-controlled approach. The first aim of the study is to examine the effects of shortened sleep on immune balance [e.g., Th1 (Interferon-IFNγ)/Th2 (Interleukin-IL-4, IL-5, IL-13)R and plasma IL-6 levels]. The second aim involves determining the effects of recovery sleep on immune balance. The third aim involves examining the extent to which changes in immune balance are associated with changes in asthma-related lung function (changes in FEV1) under conditions of shortened and recovery sleep. Results from this study ultimately will support the development feasible, ecologically valid, and clinically meaningful interventions to optimize sleep duration, immune balance, and asthma in this at-risk group.