Vitamin D, Steroids, and Asthma in African American Youth

摘要 迫切需要进一步研究，以便确定有效和可持续的战略，减少 患有哮喘的弱势青年、城市青年和少数族裔青年所经历的巨大健康差距。维生素 D缺乏症在非裔美国人中更为常见，尤其是来自城市的人。 环境或肥胖。我们和其他人促成了越来越多的证据表明维生素D 功能不全可能通过增加呼吸道感染的风险和 糖皮质激素敏感性降低。事实上，低维生素D水平最近被认为与对 外源性糖皮质激素和哮喘严重程度增加。尤其与健康差距有关的是，我们 在城市非裔美国人(AA)中显示维生素D缺乏与哮喘之间有很强的相关性 青春年华。因为居住在华盛顿特区市区的AA青少年的哮喘明显比其他地区严重 种族/族裔群体(例如，患病率比全国高出20%)15和急诊科 使用率高达全国使用率的5倍，是健康人口2010年目标使用率的近10倍)，我们 将利用我们对处于哮喘差异极端的人群的访问来检查 维生素D与慢性控制和哮喘急性严重程度的差异有关。此应用程序的总体目标是 是提供关键的流行病学/分子信息，为解释正在进行的和 即将进行的维生素D补充治疗哮喘的随机临床试验，特别是关于城市 患有哮喘的青少年。本应用程序中的实验所产生的知识对于 翻译这一廉价、容易获得的哮喘潜在疗法。我们假设低血清值 25-羟基维生素D[25(OH)D]水平与慢性哮喘控制不佳、急性哮喘加重有关 严重程度和糖皮质激素不敏感。目标1.定义哮喘表型群并确定交叉- 再生障碍性贫血和非再生障碍性贫血之间的节段性簇间和簇内与血清25(OH)D水平的相关性 青春年华。目的2.确定血清25(OH)D水平与：(A)慢性哮喘之间的前瞻性关联 控制和(B)再生障碍性贫血和非再生障碍性贫血青年之间的急性哮喘严重程度。目标3.展示 维生素D对哮喘呼吸道上皮细胞炎症介质糖皮质激素的调节作用。

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.