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 Childhood asthma has been on the rise, and is tightly linked with allergies. Improvements in our management of these conditions has not translated into less disease. Might early intervention be important to achieve optimal outcomes? Allergy and asthma pathogenesis in early childhood This model of atopy and asthma pathogenesis in early childhood can serve as the basis for a stratified approach to early interventions: click to enlarge A combination of environmental exposures and inherent biological and genetic risks formulate post-natal immune development. The heart of the problem begins when the nascent immune system develops aberrant immune responses to common, ubiquitous, unavoidable exposures. The strongest evidence of such aberrant immune development is clinical and biological manifestations of atopy. Then, chronic ongoing exposures drive inappropriate and prolonged airways injury, inflammation, and aberrant repair of injured tissues. If these aberrant processes begin in early childhood and continue through critical periods of post-natal lung growth and differentiation, then the fully developed lung may differ from normal. This may underlie the persistent asthma phenotype. Early interventions in 3 categories may lead to optimal outcomes: "Early interventions," targeting disease processes early, to normalize conditions for lung growth and development. Example: inhaled corticosteroids in young children with recurrent wheezing and at risk for persistent asthma (PEAK study, NIH — ongoing) "Secondary preventions" in young at-risk children, but prior to the establishment of chronic lung processes. Examples of previous studies: cetirizine in young children with atopic dermatitis (ETAC study) calcineurin inhibitor in young children with new-onset atopic dermatitis (SAM study) pollen allergen immunotherapy in children with allergic rhinitis (PAT study) intermittent anti-inflammatory treatment of asthma exacerbations in young children with virus-induced wheezing episodes (AIMS study, NIH Ð ongoing) "Primary preventions," for shaping and optimizing early immune development and, in doing so, override other aspects of risk. Examples of previous studies, beginning from birth or prior to birth: Lactobacillus diet supplement Omega-3 fatty acid diet supplement Dust mite allergen exposure reduction Major indoor allergen exposure reduction Allergenic food exposure reduction LiuLab publications Reviews: Liu JACI 2004: Review of early interventions Liu/Taussig/Martinez chapter 2003: considering early interventions and preventive measures, in the context of natural history Article: Marotta/Liu JACI 2003: impulse oscillometry reveals lung dysfunction in young asthma-prone children Related Hygiene Hypothesis — Nature's Immunotherapy for allergies & asthma? Endotoxin, a prototypical microbial exposure in health and disease Natural history of allergies & asthma in childhood Coming PEAK study results