Vitamin D, Steroids, and Asthma in African American Youth

描述（由申请人提供）：迫切需要进一步的研究，以确定有效和可持续的战略，以减少贫困，城市和少数民族青少年哮喘患者的巨大健康差距。维生素D缺乏症在非裔美国人（AA）中更为常见，尤其是那些来自城市环境或肥胖的人。我们和其他人已经提供了越来越多的证据，表明维生素D不足可能会增加呼吸道感染的风险，降低糖皮质激素的敏感性，从而导致更严重的哮喘。事实上，低维生素D水平最近与外源性糖皮质激素的需求和哮喘严重程度的增加有关。尤其与健康差异相关的是，我们显示了维生素D不足与城市非洲裔美国人（AA）青年哮喘之间的强烈关联。由于居住在华盛顿特区市区的AA青年的哮喘明显比其他种族/族裔更严重（例如患病率比全国发病率高20% 15，急诊科使用率高达全国发病率的5倍，是2010年健康人群目标率的近10倍），我们将利用我们对哮喘差异极端人群的访问，来检查维生素D对哮喘慢性控制和急性严重程度差异的贡献。本应用程序的总体目标是提供关键的流行病学/分子信息，为正在进行和即将进行的维生素D补充哮喘的随机临床试验提供解释，特别是关于城市AA青年哮喘。在这个应用程序的实验中产生的知识将是至关重要的翻译这种廉价的，容易获得的潜在治疗哮喘。我们假设低血清25-羟基维生素D [25(OH)D]水平与慢性哮喘控制不良、急性哮喘严重程度加重和糖皮质激素不敏感有关。目的1。定义哮喘表型集群，并确定集群间和集群内与AA青年和非AA青年之间血清25(OH)D水平的横断面关联。目标2。确定血清25(OH)D水平与：(a) AA青少年和非AA青少年之间的慢性哮喘控制和(b)急性哮喘严重程度之间的前瞻性关联。目标3。显示维生素D对哮喘气道上皮细胞中炎症介质糖皮质激素调节的影响。

DESCRIPTION (provided by applicant): 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 ill 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. PUBLIC HEALTH RELEVANCE: 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.