Childhood asthma causes substantial morbidity and health care costs. Of the 18 million asthmatics in the United States, roughly 10 million are children under the age of 16. Endotoxin, an established factor associated with airway inflammation, bronchial hyperreactivity and occupational asthma syndromes in adults, may play an important role in childhood asthma. Levels of endotoxin as high as those associated with adverse effects in occupational studies have been reported in home air samples by two groups of investigators. Endotoxin concentration in house dust has been associated with increased severity of asthma in adults. At a molecular level, endotoxin is a potent and direct stimulus for macrophage activation that does not require mature cellular immunity to exert its immuno-adjuvant effects. Thus, exposure to endotoxin early in life may play an important role in development of airways inflammation, wheeze, allergy and asthma before age five. The investigators propose to examine the role of exposure to endotoxin in a longitudinal cohort study of infants at high risk of developing asthma. This revised study proposal will take advantage of a new project (Grant # AI35786 'The Epidemiology of Home Allergens and Asthma') that will examine two main outcomes in relation to house dust mite, cockroach, and cat antigen and fungi in house dust: 1) asthma/wheeze during infancy and early childhood; and 2) allergic sensitization, as measured by skin test reactivity (during early childhood). By building on the Allergen Project, the endotoxin exposure-response analyses of these outcomes will be controlled for both allergen exposure and a wide range of other factors likely to contribute to these outcomes - with cohort identification, health data and most of the sample collection already funded. This proposal requests funds for endotoxin assay of settled dust and limited aerosol sample collection and assay, and for data analysis and interpretation of endotoxin health effects. If inflammatory-adjuvant exposure proves to be an important independent predictor of sensitization and development of asthma/wheeze in early life, it would be a finding of great public health significance. Such findings would lead to improved exposure control, and possibly indicate the need for early anti-inflammatory therapy, with potential to minimize the development of disease.
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