EARLY LIFE VITAMIN D, RACIAL DISPARITIES, AND WHEEZING

描述(由申请人提供)：这项研究将轻松、快速和有效地评估较低的产前和早期维生素D水平是否至少部分解释了非裔美国儿童比白人儿童更高的过敏性疾病结局发生率。儿科过敏和哮喘是相当大的公共卫生负担，在非裔美国人中更是如此，而且还没有得到证实的预防策略。此外，包括美国在内的西化文化中生活方式的变化导致了维生素D缺乏症的流行，与皮肤较白的人相比，这对非裔美国人的影响不成比例。维生素D缺乏是导致过敏性疾病风险增加的一个引人注目的候选因素，目前引起了极大的兴趣。这项拟议的研究将调查多种血清学水平的维生素D(25(OH)D)与皮肤点刺试验(SPT)和总IgE(SIgE)浓度和特异性血清IgE(SIgE)浓度的结果之间的关系，以及在已经建立的种族多样性出生队列中2岁时出现喘息和医生诊断的特应性皮炎的相关性。我们还没有找到任何已发表的研究，将产前、脐带和早期生命(6个月和1岁和2岁)的25(OH)D血清水平纳入到本文建议的单一过敏结果分析中。用于维生素D(25(OH)D)分析的样本已经在一家机构的生物储存库中，结果已通过医生检查确定。有明确的生物学机制可以解释产前和早期维生素D水平如何影响胎儿免疫发育和过敏性疾病的风险。以前对这些影响的人类研究明显受限于没有生物标志物的饮食维生素D量化(食物频率问卷)、主要是白人群体、主观结果和次优统计方法的使用。正在进行的，主要是非裔美国人(62%)由美国国立卫生研究院资助的出生队列研究“WHEALS”将用于这一应用。具体目标是确定早期生活25(OH)D水平(产前、脐带、6个月、1岁和2岁)在以下方面导致非裔美国儿童比白人儿童经历更差结局的程度：1)过敏原皮肤点刺试验呈阳性或sIgE试验升高的可能性增加；2)总IgE水平更高；3)特应性皮炎的发生率更高；以及4)喘息率更高(控制其他关键风险因素，如季节)。样本大小范围从448到537(因目标而异)。这项拟议的研究将利用包括倾向分数、结构方程模型和潜在变量在内的尖端统计技术来解决这些目标。随着最近国际移民组织报告的争议性和公众意识的提高，这项工作既具有重要意义，又具有紧迫性。需要对维生素D进行严格的评估，因为它是可修改的，并且可能提供一种低成本的公共卫生干预措施，有助于预防临床过敏和哮喘，并减少种族差异。 公共卫生相关性：非裔美国儿童比白人儿童更容易患过敏性疾病和喘息。社会经济地位不能完全解释这些差异。在密歇根底特律地区的一项研究中，我们试图检验早期维生素D水平是否可以解释这些种族差异。

DESCRIPTION (provided by applicant): This study will readily, quickly and efficiently evaluate whether lower prenatal and early life vitamin D levels can explain, at least in part, the higher rates of allergic disease outcomes among African American children compared with White children. Pediatric allergy and asthma are a considerable public health burden, even more so among African Americans, and there are no proven prevention strategies. Further, there is an epidemic of vitamin D deficiency caused by changes in lifestyles in westernized cultures, including the United States, which disproportionately affects African Americans compared to lighter skinned individuals. Vitamin D deficiency is a compelling candidate as a contributor to increased risk for allergic disorders and is of great current interest. This proposed study will investigate the associations between multiple serological levels of vitamin D (25(OH)D) and the outcomes of skin prick testing (SPT) and total and specific serum IgE (sIgE) concentration, as well as wheeze and doctor-diagnosed atopic dermatitis at age 2 years in an already established racially diverse birth cohort. We have not located any published research in which prenatal, cord and early life (ages 6 months and 1 and 2 years) serological levels of 25(OH)D are incorporated into a single analysis of allergic outcomes as proposed here. The samples for vitamin D (25(OH)D) analyses are already at hand in an institutional biorepository, and the outcomes have been ascertained by physician exam. There are clear biological mechanisms that explain how prenatal and early life vitamin D levels may affect fetal immune development and risk of allergic disease. Previous human studies examining these effects have been notably limited by the use of dietary vitamin D quantification (food frequency questionnaires) without biomarkers, predominantly White populations, subjective outcomes and sub-optimal statistical approaches. The ongoing, predominantly African American (62%) NIH-funded birth cohort study "WHEALS" will be used for this application. The Specific Aims are to determine the degree to which early life 25(OH)D levels (prenatal, cord, 6 months and 1 and 2 years of age) account for the worse outcomes experienced by African American children compared with White children with respect to the following: 1) an increased likelihood of having a positive allergen skin prick test or elevated sIgE test; 2) higher levels of total IgE; 3) higher rates of atopic dermatitis; and, 4) higher rates of wheeze (controlling for other key risk factors such as season). Sample size ranges from 448 to 537 (varies by aim). This proposed study will address the aims by utilizing cutting-edge statistical techniques including propensity scores, structural equation models and latent variables. With the recent controversial IOM report and increased public awareness, this work is highly significant as well as urgent. Vitamin D needs to be evaluated rigorously as it is modifiable and can potentially provide a low cost public health intervention that could help prevent clinical allergy and asthma and reduce racial disparities. PUBLIC HEALTH RELEVANCE: African American children are more likely than White children to have allergic diseases and to wheeze. Social economic status cannot fully explain these differences. We seek to examine whether early life vitamin D levels can explain these racial differences in a study in the Detroit, Michigan area.