Environmental Determinants of Sleep Disturbance: Role of Ambient Air Pollution

睡眠障碍影响数百万美国人，每年花费数十亿美元。睡眠障碍的累积长期影响与广泛的有害健康后果相关，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。睡眠障碍患病率的地理差异已被记录了几十年，但造成睡眠障碍的环境因素在很大程度上仍然未知。动物实验表明，通过改变与睡眠有关的神经递质，臭氧暴露会导致睡眠紊乱。最近的空气污染毒性研究表明，颗粒物（PM）暴露可诱导神经毒性和不良全身反应，包括氧化应激和炎症反应。虽然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，但尚未对这种病理生理学上合理的影响进行流行病学调查。拟议的队列研究针对NIH确定的一个重要人群亚组，旨在调查环境空气污染物作为绝经后妇女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）和两项NIH支持的研究，以有效的方式解决这些重要问题。我们将研究暴露于环境空气污染和睡眠障碍之间的关联，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岁的女性的地理多样性队列中的睡眠障碍的空间变异性做出贡献。所提出的研究利用了关于良好表征的WHI-CT队列的睡眠障碍和生物物理属性的现有高质量纵向数据。此外，我们能够将所有WHI-CT参与者的空气污染数据纳入NIEHS资助的辅助研究，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。对于本申请，将在多水平分析中检查68，133名妇女的纵向睡眠概况，包括经验证的WHI-失眠评定量表，以确定其与居住水平暴露于环境空气污染物的相关性，主要关注PM和臭氧。将分析这些推定的协会由个人的生物物理属性的潜在修改，以确定亚群更容易受到睡眠障碍相关的不利的周围环境。这种对暴露于环境空气污染的神经行为影响的创新流行病学调查将扩展我们在睡眠障碍环境决定因素研究新领域的知识。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数百万美国人，并增加肥胖，高血压，糖尿病和心血管疾病的风险。动物实验已经证明了暴露在空气污染中会导致睡眠紊乱，但还没有研究将环境空气污染作为人类睡眠障碍的决定因素。这项关于环境空气污染对睡眠障碍影响的首次流行病学研究的预期结果将对睡眠障碍患者的公共卫生政策和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.