Vitamin D and Susceptibility to Inhaled Pollutants in Urban Children with Asthma

描述（由申请人提供）：拟议的项目承诺将是一个丰富的培训经验，将使我能够开发临床研究所需的技能。它通过严格的研究计划，相关的课程和监督的专门指导相结合来实现这一目标。以下是研究建议的摘要。在美国，城市少数民族儿童人群的哮喘负担不成比例。有几个因素可能导致这种差异，包括高度暴露于环境污染物和过敏原，不良饮食以及贫困的其他不利因素。最近的注意力集中在维生素D的抗氧化和免疫调节作用，这可能会对疾病的发病率产生保护作用，一些临床观察和横断面研究支持低维生素D水平可能会导致更严重的过敏和哮喘表现。流行病学研究，包括我们自己在巴尔的摩的初步调查，已经发现相当大比例的非裔美国贫民区哮喘儿童的血清维生素D水平远低于推荐水平，并且在这些儿童中，室内颗粒物（PM）是哮喘发病的重要原因。因此，我们建议确定在这样一个高度受影响和脆弱的人群中，较低水平的维生素D是否会增加他们对吸入污染物的易感性。为了实现这一目标，我们将把这项拟议的研究嵌套在现有的资助（城市环境中的儿童哮喘中心DISCOVER #1 P50 ES 015903）中，该中心目前正在巴尔的摩城市招募130名5-12岁的哮喘儿童，主要是黑人，以研究空气污染诱导肺部炎症和氧化应激的机制。该项目提案有三个新目标。首先，为了更好地了解维生素D水平与哮喘健康之间的关系，我们将在一年中的每个季节重复测量每个受试者的血清维生素D水平、每日哮喘症状和药物使用情况，以及在4个为期一周的时间段内每天两次的肺功能。其次，为了确定不同水平的维生素D是否会改变对空气污染的炎症反应，我们还将监测每个孩子一整天暴露于环境PM的情况，同时测量血液、尿液和鼻腔灌洗液中存在的氧化应激和炎症的生物标志物。最后，我们将收集有关阳光照射、皮肤类型和饮食摄入的信息，以评估这一长期低水平人群维生素D状况的决定因素，为未来改善哮喘健康的公共卫生战略做准备。 公共卫生相关性：哮喘发作在城市非洲裔美国儿童中尤为严重，并造成重大的个人，经济和社会成本。最近的研究表明，这些儿童中的大多数血液中维生素D水平较低，并且水平越低，他们的哮喘症状似乎越严重。我们想知道，低维生素D水平是否会增加儿童受常见环境因素影响的风险;如果是这样，那么改善他们的维生素D状况可能最终会保护城市少数民族儿童免受高疾病负担的影响。

DESCRIPTION (provided by applicant): The proposed project promises to be a rich training experience that will allow me to develop the skills necessary for clinical research. It achieves this through a combination of a rigorous research plan, relevant coursework, and supervised dedicated mentorship. Below is a summary of the research proposal. The urban minority pediatric population in the United States has a disproportionate burden of asthma. Several factors may contribute to this disparity, including high exposure to environmental pollutants and allergens, a poor diet, and other disadvantages of poverty. Recent attention has focused on the antioxidant and immune-modulatory role of vitamin D which may confer a protective effect on disease morbidity, and several clinical observational and cross-sectional studies support that low vitamin D levels may lead to greater allergic and asthma manifestations. Epidemiological studies, including our own preliminary investigations in Baltimore, have discovered that a significant proportion of African-American inner-city children with asthma have well below the recommended levels of serum vitamin D, and that, in these same children, indoor particulate matter (PM) is a significant cause of asthma morbidity. We therefore propose to determine whether lowerlevels of vitamin D, in such a highly-affected and vulnerable population, may increase their susceptibility to inhaled pollutants. To achieve this goal, we will nest this proposed study within an existing grant (The Center for Childhood Asthma in the Urban Environment DISCOVER # 1P50ES015903), which is currently recruiting 130 predominantly-black children with asthma, ages 5-12 years, in urban Baltimore to study the mechanisms by which air pollution induces lung inflammation and oxidative stress. This project proposal has three novel aims. First, to better understand the relationship between vitamin D levels and asthma health, we will be repeatedly measuring each subject' s serum vitamin D levels, daily asthma symptoms and medication use, and twice-daily lung function during 4 one-week periods in each season of the year. Second, to determine if varying levels of vitamin D modify the inflammatory response to air pollution, we will also be monitoring each child' s personal exposure to environmental PM throughout the day and simultaneously be measuring biomarkers of oxidative stress and inflammation present in blood, urine, and nasal lavage fluid. Finally, we will be collecting information regarding sun exposure, skin type, and dietary intake in order to assess the determinants of vitamin D status in this chronically low population, in preparation for future public health strategies directed towards improving asthma health. PUBLIC HEALTH RELEVANCE: Asthma attacks are particularly severe among urban African-American children and account for significant personal, economic, and social costs. Recent studies show that the majority of these children have low blood levels of vitamin D, and that the lower their levels, the worse their asthma symptoms seem to be. We would like to understand if low vitamin D levels put children at increased risk to be affected by common environmental triggers; if true, then improving their vitamin D status may ultimately protect urban minority children from a high burden of disease.