HYGIENE  ENDOTOXIN  EARLY INTERVENTION  CHILDHOOD ASTHMA  INNER CITY ASTHMA  RHINOSINUSITIS  NATURAL HISTORY Andrew H. Liu, M.D. Staff Contact in association with:

click to enlarge The hygiene hypothesis purports that Nature may "immunize" against the development of allergic diseases and asthma through naturally occurring infections and microbial exposures of the respiratory and GI tracts (and possibly the skin) in early life. How does Nature separate the benefit of microbial exposures from the harm of infections? By better understanding Nature's ways, we hope to discover important clues for early interventions that can safely improve allergy and asthma outcomes. click to enlarge How could microbes alter immune responses and promote healthful immune development to prevent allergy and asthma? The classic paradigm is based on the typical, protective Th1 responses to microbes, which down-modulate Th2 development and atopy (i.e., high-affinity IgE to allergens). This keeps environmental exposures from becoming allergens. Th1 immune responses also improve host defense by inducing anti-viral mechanisms that keep respiratory viruses from proliferating in respiratory epithelium and spreading down the airways. Th1 immune responses during airways injury and inflammation also inhibit aberrant repair processes that underlie pathologic tissue changes in asthma. For example, IFN-g inhibits mucous gland and smooth muscle hyperplasia, fibrotic repair processes, and mast cell activation. Microbes also induce regulatory immune responses (e.g., regulatory T lymphocytes) to limit immune activation and inflammation when they are no longer needed, to prevent further tissue damage from "friendly fire". To summarize, optimal immune development promoted by microbial exposures would lead to: No environmental exposures seen by the immune system as allergens Good host defense Normal repair of tissue injury No "friendly fire" injury LiuLab publications Reviews: Liu/Murphy JACI 2003: Weighing the clinical evidence on the hygiene hypothesis Liu J Respir Dis 2004: Editorial with pro-con debate on the hygiene hypothesis Related Endotoxin, a prototypical microbial exposure in health and disease Early Intervention for allergic diseases & asthma Natural history of allergies & asthma in childhood Coming Hygiene Hypothesis book