Trial of Infant Probiotic Exposure on Developing Asthma

描述（由申请方提供）：卫生学假设表明，不存在内毒素暴露会导致不利的Th 1/Th 2平衡。婴儿期受控的抗原暴露可能有助于建立Th 1/Th 2平衡，阻断哮喘的发作或进展。乳酸杆菌是一种细菌，在典型的儿科饮食中的许多食物中发现，并被用作预防腹泻的补充剂。由于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，乳酸杆菌是一种理想的细菌，可用作暴露来测试卫生假设。我们假设这样的暴露可能会阻止或延迟哮喘早期标志物的发展。使用随机安慰剂对照试验设计，我们将测量6个月的每日接触乳杆菌作为婴儿配方奶粉补充剂对生命最初3年内免疫系统和哮喘发展的影响。我们将测量抗原暴露对以下指标的存在和出现时间的影响：（1）哮喘发展的早期临床标志物（频繁喘息、无感冒的喘息、鼻炎和特应性皮炎）;（2）哮喘发展的早期免疫学标志物（嗜酸性粒细胞增多症，IgE）;和（3）辅助性T细胞表型（Th-1 vs Th-2）的发展。我们将通过测量全血淋巴细胞对刺激物的反应来表征Th表型，重点是Th 1（IFN-γ，IL-12）和Th 2细胞因子（IL-10，IL-4，IL-13），以及实时逆转录酶聚合酶链反应（RT-PCR）和PCR扩增（TaqMan）来定量RNA转录物。临床和免疫学标志物将测量至3岁。将使用日记、药丸计数和乳酸杆菌粪便培养物评估依从性。我们将使用意向治疗分析，并使用多变量回归和生存分析技术控制家庭、环境、饮食和人口统计学因素对结局的影响。我们预计，与对照组相比，接受乳酸杆菌的受试者将减少和延迟哮喘标志物的发展，并更有可能发展为Th 1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.