Environmental Determinants of Sleep Disturbance: Role of Ambient Air Pollution

描述(申请人提供)：睡眠障碍影响数百万美国人，每年造成数十亿美元的损失。睡眠障碍的累积长期影响与广泛的有害健康后果有关，包括全身炎症、免疫功能障碍和神经内分泌异常，导致肥胖、高血压、糖尿病和心血管疾病的风险增加。几十年来，睡眠障碍患病率的地理差异已经被记录在案，但导致睡眠障碍的环境因素在很大程度上仍不清楚。动物实验已经证明，暴露在臭氧中会通过改变与睡眠相关的神经递质而导致睡眠紊乱。最近对空气污染毒性的研究表明，暴露于颗粒物(PM)可引起神经毒性和不良全身反应，包括氧化应激和炎症反应。尽管这些毒理学数据支持环境空气污染物在睡眠障碍中的作用，但还没有对这种病理生理学上可信的影响进行流行病学调查。这项拟议的队列研究针对的是美国国立卫生研究院确定的一个重要人群亚群，旨在调查环境空气污染物是绝经后女性睡眠障碍的新决定因素。我们利用已完成的妇女健康倡议临床试验(WHI-CT)和美国国立卫生研究院资助的两项研究，有效地解决这些重要问题。我们将研究暴露在环境空气污染和睡眠障碍之间的联系，并评估环境空气污染物的假设影响如何在研究开始时对年龄在50-79岁之间的不同地理位置的女性队列的睡眠障碍的空间变异性做出贡献。这项建议的研究利用了现有的关于睡眠障碍的高质量纵向数据和特征良好的WHI-CT队列的生物物理属性。此外，我们能够纳入由NIEHS资助的辅助研究收集的所有WHI-CT参与者的空气污染数据，并根据EPA空气质量系统中记录的标准污染物数据验证其暴露估计方法。在这项应用中，68,133名女性的纵向睡眠状况，包括经过验证的WHI-失眠评定量表，将在多水平的分析中被检查，以确定她们与居住水平暴露在环境空气污染物中的相关性，主要关注PM和臭氧。这些假定的相关性的潜在修改将被分析，以确定更容易受到与不利环境有关的睡眠干扰的亚群。这项对暴露在环境空气污染中的神经行为影响的创新性流行病学调查将扩展我们在睡眠障碍环境决定因素研究的新领域的知识。睡眠障碍的环境决定因素：环境空气污染项目的作用叙述睡眠障碍影响着数百万美国人，并增加了肥胖、高血压、糖尿病和心血管疾病的风险。动物实验表明，暴露在空气污染中会导致睡眠紊乱，但还没有研究表明环境空气污染作为人类睡眠障碍的决定因素所起的作用。这项拟议的首个关于环境空气污染对睡眠障碍影响的流行病学研究的预期结果将对公共卫生政策和睡眠障碍患者的临床护理产生重大影响。

DESCRIPTION (provided by applicant): Sleep disturbance affects millions of Americans and costs billions of dollars each year. The cumulative long-term effects of sleep disturbance have been associated with a wide range of deleterious health consequences including systemic inflammation, immune dysfunction, and neuroendocrine abnormalities, resulting in increased risks for obesity, hypertension, diabetes, and cardiovascular diseases. Geographic difference in the prevalence of sleep disturbance has been documented for several decades, but the contributing environmental factors remain largely unknown. Animal experiments have demonstrated disorganization of sleep induced by exposure to ozone, through alterations of sleep-related neurotransmitters. Recent research in air pollution toxicity has shown that particulate matter (PM) exposures can induce both neurotoxic and adverse systemic reactions including oxidative stress and inflammatory responses. Although these toxicological data support the role of ambient air pollutants in sleep disturbance, no epidemiologic investigation has been conducted for this pathophysiologically plausible effect. The proposed cohort study targets an important population subgroup identified by the NIH and aims to investigate ambient air pollutants as novel determinants of sleep disturbance in postmenopausal women. We draw on the completed Women's Health Initiative Clinical Trials (WHI-CT) and two NIH-supported studies to address these important questions in an efficient manner. We will examine the association between exposure to ambient air pollution and sleep disturbance and assess how the hypothesized effects of ambient air pollutants contribute to the spatial variability of sleep disturbance in a geographically-diverse cohort of women aged 50-79 at study inception. The proposed study takes advantage of the extant high-quality longitudinal data on sleep disturbance and biophysical attributes of the well- characterized WHI-CT cohort. Further, we are able to incorporate the air pollution data for all WHI-CT participants assembled by an NIEHS-funded ancillary study and have validated its exposure estimation methodology based on the criteria pollutants data recorded in the EPA Air Quality System. For this application, longitudinal sleep profiles of 68,133 women, including the validated WHI-Insomnia Rating Scale, will be examined in multi-level analyses for their associations with residence-level exposure to ambient air pollutants, with primary focus on PM and ozone. Potential modifications of these putative associations by individual's biophysical attributes will be analyzed to identify subpopulations more susceptible to sleep disturbance related to adverse ambient environment. This innovative epidemiologic investigation of neurobehavioral effects of exposure to ambient air pollution will extend our knowledge in a novel area of research on environmental determinants of sleep disorders. Environmental Determinants of Sleep Disturbance: Role of Ambient Air Pollution Project Narrative Sleep disturbance affects millions of Americans and increases risks for obesity, hypertension, diabetes, and cardiovascular diseases. Animal experiments have demonstrated disorganization of sleep induced by exposure to air pollution, but no studies have examined the role of ambient air pollution as a determinant of sleep disturbance in humans. Expected results from this proposed first epidemiologic study on the effect of ambient air pollution on sleep disturbance will have major implications for public health policies and clinical care for patients with sleep disorders.