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: 7102572
• 负责人: Michael D Cabana
• 金额: $ 48.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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/7102572
• 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）：卫生假说表明，不接触内毒素会导致不利的 Th1/Th2 平衡。婴儿期控制抗原暴露可能有助于建立 Th1/Th2 平衡，从而阻止哮喘的发作或进展。乳酸菌是一种在典型儿科饮食中的许多食物中发现的细菌，被用作预防腹泻的补充剂。由于其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，乳酸菌是一种理想的细菌，可用作测试卫生假设的暴露物。我们假设这种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 个月每日接触乳杆菌（作为婴儿配方奶粉补充剂）对生命前 3 年免疫系统和哮喘发展的影响。我们将测量抗原暴露对以下情况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、非感冒喘息、鼻炎和特应性皮炎）； (2) 哮喘发展的早期免疫标志物（嗜酸性粒细胞增多，IgE）； (3) T辅助表型的发展（Th-1 vs Th-2）。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，重点关注 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式反应 (RT-PCR) 和 PCR 扩增 (TaqMan) 来量化 RNA 转录本。临床和免疫学标志物将在 3 岁时进行测量。将使用日记、药丸计数和乳酸菌粪便培养物来评估依从性。我们将使用意向治疗分析，并使用多元回归和生存分析技术来控制家庭、环境、饮食和人口因素对结果的影响。我们预计，与对照组相比，接受乳酸菌治疗的受试者哮喘标记物的发展会减少并延迟，并且出现 Th1 表型的可能性更大。