Trial of Infant Probiotic Exposure on Developing Asthma

描述(由申请人提供)：卫生学假说认为，缺乏内毒素暴露会导致Th1/Th2平衡不良。在婴儿期控制抗原暴露可能有助于建立Th1/Th2平衡，阻止哮喘的发生或发展。乳杆菌是一种细菌，在典型的儿科饮食中存在于许多食物中，被用作预防腹泻的补充剂。由于乳杆菌在预防特应性皮炎方面的安全性、可行性和早期有希望的结果，乳杆菌是一种理想的细菌，可以用来作为检验卫生假说的暴露。我们推测，这样的暴露可能会阻止或延迟哮喘早期标志物的发展。采用随机安慰剂对照试验设计，我们将测量作为婴儿配方奶粉补充剂的乳酸菌每日暴露6个月对免疫系统和生命头3年内哮喘发生的影响。我们将测量抗原暴露对(1)哮喘发生的早期临床标志物(频繁喘息、无感冒喘息、鼻炎和特应性皮炎)的出现和出现的时间的影响；(2)哮喘发生的早期免疫学标志物(嗜酸性粒细胞增多症，IgE)；以及(3)T辅助细胞表型的发展(Th-1与Th-2)。我们将通过检测全血淋巴细胞对刺激剂的反应，重点关注Th1(干扰素-γ，IL-12)和Th2细胞因子(IL-10，IL-4，IL-13)，以及实时逆转录聚合酶链式反应(RT-PCR)和聚合酶链式反应(TaqMan)来定量RNA转录产物来表征Th的表型。临床和免疫学标志物将在3岁以下进行测量。依从性将使用日记、药片计数和乳杆菌粪便培养进行评估。我们将使用意向治疗分析，并将使用多元回归和生存分析技术控制家庭、环境、饮食和人口统计因素对结果的影响。我们预计，与对照组相比，接受乳杆菌治疗的受试者哮喘标志物的发展将会减少和延迟，并更有可能发展为Th1表型。

DESCRIPTION (provided by applicant): The hygiene hypothesis suggests that the absence of endotoxin exposure leads to an unfavorable Th1/Th2 balance. A controlled antigen exposure during infancy may help establish a Th1/Th2 balance that blocks the onset or progression of asthma. Lactobacillus is a bacterium found in many foods in the typical pediatric diet, and is used as a supplement to prevent diarrhea. Due to the safety, feasibility and early promising results in preventing atopic dermatitis, Lactobacillus is an ideal bacterium to use as an exposure to test the hygiene hypothesis. We hypothesize that such an exposure may block or delay development of early markers of asthma. Using a randomized placebo-controlled trial design, we will measure the effect of a 6-month daily exposure of Lactobacillus, as an infant formula supplement, on immune system and asthma development during the first 3 years of life. We will measure the effect of the antigen exposure on the presence and time to presentation of (1) early clinical markers for asthma development (frequent wheezing, wheezing without colds, rhinitis, and atopic dermatitis); (2) early immunologic markers for asthma development (eosinophilia, IgE); and (3) development of a T-helper phenotype (Th-1 vs Th-2). We will characterize the Th phenotype by measuring the whole blood lymphocyte response to stimulants, focusing Th1 (IFN-gamma, IL-12) and Th2 cytokines (IL-10, IL-4, IL-13), as well as real-time reverse transcriptase polymerase chain reaction (RT-PCR) with PCR amplification (TaqMan) to quantify RNA transcripts. Clinical and immunologic markers will be measured up to 3 years of age. Adherence will be assessed using diaries, pill count, and Lactobacillus stool cultures. We will use intention-to-treat analysis and will control for the impact of family, environmental, diet, and demographic factors on outcomes using multivariate regression and survival analysis techniques. We expect that when compared to controls, subjects receiving Lactobacillus will have decreased and delayed development of markers for asthma, and a greater likelihood of developing a Th1 phenotype.