Vitamin D, Steroids, and Asthma in African American Youth

摘要 迫切需要进一步研究，以确定有效和可持续的战略， 贫困、城市和少数民族哮喘青年所经历的巨大健康差异。维生素 D缺乏症在非洲裔美国人（AA）中更为常见，尤其是来自城市的人 环境或肥胖。我们和其他人已经为越来越多的证据做出了贡献， 营养不足可能通过增加呼吸道感染的风险导致更严重的哮喘， 糖皮质激素敏感性降低。事实上，维生素D水平低最近与需要 外源性糖皮质激素和哮喘严重程度增加。与健康差距特别相关的是，我们 在城市非洲裔美国人（AA）中，维生素D不足与哮喘之间存在很强的关联 青年因为居住在华盛顿市区的AA青少年的哮喘明显比其他地区的青少年严重， 种族/族裔群体（例如，发病率比全国发病率高20%， 利用率达到全国利用率的5倍，接近2010年健康人口目标利用率的10倍）， 我将利用我们对哮喘差异极端人群的访问，检查 维生素D对慢性控制和哮喘急性严重程度的差异。此应用程序的总体目标 是提供关键的流行病学/分子信息，为解释正在进行的 即将进行的补充维生素D治疗哮喘的随机临床试验，特别是在城市 青少年哮喘在这个应用程序中的实验所产生的知识将是至关重要的， 翻译这种便宜，容易获得的哮喘潜在疗法。我们假设低血清 25-羟维生素D [25（OH）D]水平与慢性哮喘控制不良、急性哮喘恶化 严重性和糖皮质激素不敏感性。AIM 1.定义哮喘表型簇并确定交叉- AA和非AA患者血清25（OH）D水平的分段群间和群内相关性 青年AIM 2.确定血清25（OH）D水平与以下因素之间的前瞻性关联：（a）慢性哮喘 对照组和（B）AA和非AA青年内和之间的急性哮喘严重程度。AIM 3.显示效果的 维生素D对糖皮质激素调节哮喘气道上皮细胞炎症介质的影响

Abstract Further studies are urgently needed in order to identify effective and sustainable strategies for reducing the dramatic health disparities experienced by disadvantaged, urban, and minority youth with asthma. Vitamin D deficiency is more common among African American (AA) individuals, especially those from urban environments or with obesity. We and others have contributed to increasing evidence that vitamin D insufficiency may contribute to more severe asthma through increased risk of respiratory infection and decreased glucocorticoid sensitivity. Indeed, low vitamin D levels were recently linked with the need for exogenous glucocorticoids and increased asthma severity. Particularly relevant to health disparities, we showed a strong association between vitamin D insufficiency and asthma in urban African American (AA) youth. Because AA youth residing in urban Washington, DC have markedly worse asthma than other racial/ethnic groups (e.g. prevalence rate 20% higher than the national rate 15 and emergency department utilization rates up to 5 times the national rates and nearly 10 times the Healthy People 2010 target rate), we will utilize our access to this population at the extreme of asthma disparities to examine the contribution of vitamin D to disparities in the chronic control and acute severity of asthma. The overall goal of this application is to provide critical epidemiological/molecular information that will inform the interpretation of ongoing and impending randomized clinical trials of vitamin D supplementation in asthma, especially with regard to urban AA youth with asthma. The knowledge generated by the experiments in this application will be crucial to translation of this inexpensive, easily-accessible potential therapy for asthma. We hypothesize that low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with poor chronic asthma control, worse acute asthma severity, and glucocorticoid insensitivity. AIM 1. Define asthma phenotypic clusters and determine cross- sectional inter- and intra-cluster associations with serum 25(OH)D levels within and between AA and non-AA youth. AIM 2. Determine prospective associations among serum 25(OH)D levels and: (a) chronic asthma control and (b) acute asthma severity within and between AA and non-AA youth. AIM 3. Show the effect of vitamin D on glucorticoid regulation of inflammatory mediators in asthmatic airway epithelial cells.