TRIAL OF INFANT PROBIOTIC SUPPLEMENTATION TO PREVENT ASTHMA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。人们对哮喘的初级预防知之甚少。卫生假说认为，没有细菌接触会导致免疫系统的不利平衡。控制细菌接触可能有助于在发育中的免疫系统中创造更有利的平衡，并降低患哮喘的风险。乳酸菌是一种存在于典型儿科饮食（如酸奶）中许多食物中的细菌，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，乳杆菌是一种理想的细菌，可以用来测试这种卫生假设，看看它是否能创造一个有利的免疫平衡，以帮助预防哮喘。采用随机安慰剂对照试验设计，我们将测量6个月每日暴露乳酸菌作为婴儿配方奶粉补充剂对3岁前免疫系统和哮喘发展的影响。新生婴儿将被随机分为两组，一组在6个月内每天喂食少量乳酸菌补充剂，另一组在6个月内每天喂食少量安慰剂。我们将测量乳酸菌对哮喘发展的早期临床标志（频繁喘息、喘息无感冒、鼻炎和特应性皮炎）的存在和出现时间的影响；(2)哮喘发展的早期免疫标志物（嗜酸性粒细胞增多、IgE）；此外，我们将(3)跟踪免疫系统中标志物的发展，通过测量全血淋巴细胞对兴奋剂的反应来评估Th表型的发展，聚焦Th1 （ifn - γ, IL-12）和Th2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）来量化RNA转录物。临床和免疫指标将被测量到3岁。在最初的六个月里，我们还将通过要求父母填写日记来收集数据，了解父母实际服用补充剂的频率，以及前三次随访时的药片数量。在我们的数据分析中，我们将使用意向治疗分析，并将使用多变量回归和生存分析技术控制家庭、环境、饮食和人口因素对结果的影响。我们预计，与对照组相比，接受乳酸杆菌治疗的受试者哮喘标志物的发展将减少和延迟，Th1表型的可能性更大。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Little is known about the primary prevention of asthma. The hygiene hypothesis suggests that the absence of bacterial exposure leads to an unfavorable balance of the immune system. A controlled bacterial exposure may help create a more favorable balance in the developing immune system and lead to decreased risk of developing asthma. Lactobacillus is a bacterium found in many foods in the typical pediatric diet (e.g., yogurt), 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 this hygiene hypothesis and see if it can create a favorable immunologic balance to help prevent 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. Newborn babies will be randomized to either a group that will be fed a small amount of Lactobacillus supplement each day for 6 months, or a group that will be fed a small amount of placebo each day for 6 months. We will measure the effect of the Lactobacillus on the presence and time to presentation of (1) early clinical markers for asthma development (frequent wheezing, wheezing without colds, rhinitis, and atopic dermatitis); and (2) early immunologic markers for asthma development (eosinophilia, IgE); In addition, we will (3) follow the development of markers in the immune system to assess the development of 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. During the first six months we will also collect data on how frequently parents are actually feeding the supplement by asking parents to complete diaries, as well as pill counts at the first 3 follow-up visits. In our analysis of the data, 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.