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

项目摘要/摘要 患有哮喘的城市儿童睡眠不足的风险很高，因为环境危害睡眠和 哮喘管理。此外，这一群体还遭受着免疫平衡的改变，这是一个关键的生物学过程 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疾病 以Th2为标志的T辅助细胞1(Th1)/2(Th2)细胞因子失衡引起的炎症性疾病 细胞因子(IL-4、IL-5和/或IL-13)占优势。在健康成年人中的实验结果表明，缩短的 睡眠增加炎性细胞因子(如IL-6)和某些Th2细胞因子水平，恢复睡眠 限制睡眠会促进免疫平衡的恢复。睡眠时间是否对睡眠起关键作用 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)睡眠持续时间是临床护理中忽视的一种可改变的行为 患有哮喘的城市儿童，以及(3)实验数据对于测试睡眠时间作为一种 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和充足睡眠的城市儿童(N=204，年龄8-9岁) 持续时间(9-11小时)谁将完成为期4周的受试者内方案，其中包括3个预定的实验 睡眠状况：(1)1周稳定睡眠(个体化，上床时间9-11小时)，(2)1周睡眠缩短 (3)恢复睡眠2周(卧床时间增加1.5h)。我们会监控 每天的睡眠时间(活动描记)和肺功能(家庭肺活量测定)，并每周评估免疫生物标志物 在睡眠时间缩短的中点。为了控制学习时间的影响，我们的样本中有三分之一将只收到 在为期4周的方案中稳定了睡眠时间表。在这个项目中，我们将只研究城市儿童 获得充足睡眠(9-11小时，在国家指南内)的过敏性哮喘患者。我们缩短的睡眠协议 将模拟患有哮喘的城市儿童由于哮喘和/或城市环境而可能经历的睡眠不足。 此外，我们的恢复睡眠协议模拟了睡眠缩短后的睡眠优化干预 以一种控制良好的方法。 这项研究的第一个目的是检查睡眠减少对免疫平衡的影响[例如，Th1 (干扰素-干扰素γ)/Th2(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以下方面的程度 免疫平衡的哪些改变与哮喘相关的肺功能改变有关(改变 FEV1)在睡眠缩短和恢复的条件下。这项研究的结果最终将支持 开发可行的、生态上有效的、具有临床意义的干预措施，以优化睡眠时间， 免疫平衡，以及这一高危人群中的哮喘。

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.