EARLY LIFE VITAMIN D, RACIAL DISPARITIES, AND WHEEZING

描述（由申请人提供）：本研究将方便、快速和有效地评估产前和生命早期较低的维生素D水平是否可以解释（至少部分解释）非裔美国儿童与白人儿童相比过敏性疾病结果的较高发生率。儿科过敏和哮喘是一个相当大的公共卫生负担，在非裔美国人中更是如此，而且没有经过证实的预防策略。此外，在包括美国在内的西化文化中，生活方式的改变导致了维生素D缺乏症的流行，与肤色较浅的人相比，非洲裔美国人受到的影响尤为严重。维生素D缺乏是一个令人信服的候选因素，是过敏性疾病风险增加的一个因素，目前引起了人们的极大兴趣。本研究将调查多种血清学水平维生素D （25(OH)D）与皮肤点刺试验（SPT）结果、总血清和特异性血清IgE （sIgE）浓度、喘息和医生诊断的2岁时特应性皮炎之间的关系，该研究已经建立了种族多样化的出生队列。我们没有找到任何已发表的研究，其中产前、脐带和生命早期（6个月、1岁和2岁）25(OH)D的血清学水平被纳入本文提出的过敏结果的单一分析。维生素D （25(OH)D）分析的样本已经在一个机构生物储存库中，结果已经由医生检查确定。有明确的生物学机制可以解释产前和生命早期维生素D水平如何影响胎儿免疫发育和过敏性疾病的风险。先前的人类研究检查了这些影响，但由于使用饮食维生素D量化（食物频率问卷）而没有生物标志物，主要是白人人群，主观结果和次优统计方法，这些研究明显受到限制。正在进行的主要是非裔美国人（62%）的美国国立卫生研究院资助的出生队列研究“WHEALS”将用于该应用。具体目的是确定生命早期25（OH)D水平（产前、脐带、6个月、1岁和2岁）对非洲裔美国儿童与白人儿童相比在以下方面经历的更差结果的影响程度：1）过敏原皮肤点刺试验阳性或sIgE试验升高的可能性增加；2)总IgE水平升高；3)特应性皮炎发病率较高；4)喘息率更高（控制其他关键风险因素，如季节）。样本量从448到537不等（因目标而异）。本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一问题。随着最近有争议的国际移民组织报告和公众意识的提高，这项工作非常重要和紧迫。维生素D需要严格评估，因为它是可修改的，并且可能提供低成本的公共卫生干预，有助于预防临床过敏和哮喘，并减少种族差异。

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.