Trial of Infant Probiotic Exposure on Developing Asthma

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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.