TRIAL OF INFANT PROBIOTIC SUPPLEMENTATION TO PREVENT ASTHMA

婴儿益生菌补充剂预防哮喘的试验

• 批准号: 7376595
• 负责人: Michael D Cabana
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376595
• 关键词: asthma; balance; child rearing; diet; immune system; lead; parents; phenotype; placebos

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。对哮喘的一级预防知之甚少。卫生假说表明，没有细菌暴露会导致免疫系统的不利平衡。受控的细菌暴露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。乳酸杆菌是一种在典型的儿科饮食中的许多食物中发现的细菌（例如，酸奶），并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，可用作暴露来测试这种卫生假设，看看它是否能创造有利的免疫平衡来帮助预防哮喘。 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。新生儿将被随机分为两组，一组每天喂食少量乳酸菌补充剂，持续6个月，另一组每天喂食少量安慰剂，持续6个月。 我们将测量乳酸杆菌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）;和（2）哮喘发展的早期免疫学标志物（嗜酸性粒细胞增多症，IgE）;此外，本发明还提供了一种方法，我们会（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刺激物的反应来评估Th表型的发展，聚焦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）以定量RNA转录物。 临床和免疫学标志物将测量至3岁。在前六个月，我们还将通过要求父母填写日记以及前3次随访时的药丸数量来收集有关父母实际喂养补充剂的频率的数据。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。