Trial of Infant Probiotic Exposure on Developing Asthma

婴儿益生菌暴露对发生哮喘的试验

• 批准号: 6831001
• 负责人: Michael D Cabana
• 金额: $ 49.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831001
• 关键词: Lactobacillus; antigen presentation; asthma; atopic dermatitis; baby food; biomarker; biotechnology; biotherapeutic agent; clinical research; clinical trials; developmental immunology; diet therapy; dietary supplements; eosinophilia; feces analysis; helper T lymphocyte; human subject; human therapy evaluation; immunoglobulin E; immunopathology therapy; infant human (0-1 year); longitudinal human study; nutrition related tag; patient oriented research; personal log /diary; polymerase chain reaction; rhinitis; therapy compliance

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.

描述（由申请人提供）：卫生假设表明，缺乏内毒素暴露会导致不利的TH1/TH2平衡。婴儿期受控的抗原暴露可能有助于建立阻塞哮喘发作或进展的TH1/TH2平衡。乳杆菌是在典型的小儿饮食中许多食物中发现的细菌，被用作预防腹泻的补充剂。由于安全性，可行性和早期有希望的结果，可防止特征性皮炎，乳酸杆菌是一种理想的细菌，用于检验卫生假设。我们假设这种暴露可能会阻止或延迟哮喘早期标记的发展。使用随机的安慰剂对照试验设计，我们将衡量乳酸杆菌每天6个月暴露作为婴儿配方奶粉，对免疫系统和哮喘发育的影响。我们将衡量抗原暴露对哮喘发育的早期临床标记的存在和时间的影响（频繁喘息，喘息，没有感冒，鼻炎和特应性皮炎）； （2）哮喘发育的早期免疫学标记（嗜酸性粒细胞，IgE）； （3）开发T-馆表型（TH-1与TH-2）。我们将通过测量对刺激剂的全血淋巴结反应来表征TH1（IFN-GAMMA，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）与PCR Amplificatifiation ranfiatifiatival ranna（taqMan）。临床和免疫标记将测量长达3岁。依从性将使用日记，药丸计数和乳杆菌且粪便培养物进行评估。我们将使用意向性治疗分析，并使用多元回归和生存分析技术来控制家庭，环境，饮食和人口统计学因素对结果的影响。我们预计，与对照组相比，接受乳杆菌的受试者将减少和延迟哮喘标记的发育，并且更有可能发展Th1表型。