TRIAL OF INFANT PROBIOTIC SUPPLEMENTATION TO PREVENT ASTHMA

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.