Airway as Target Organ in Infants with Atopic Dermatitis

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DESCRIPTION (provided by applicant): Asthma is a disease characterized by recurrent episodes of airway obstruction, by airway hyperresponsiveness, and airway inflammation. There is a strong genetic component to asthma; family history of asthma and allergy are strongly associated with the risk of an infant developing asthma and the persistence of asthma symptoms. Children with early onset of persistent asthma are also more likely to be atopic individuals, who develop eczema during infancy and then progress to having gastro-intestinal symptoms of specific food intolerance and then to having respiratory symptoms. Of atopic infants, more than 50% subsequently develop recurrent respiratory symptoms and asthma. This progression of atopic symptoms has been referred to as "the allergic march", which results from complex interactions between genetic susceptibility and environmental factors. The presence of an inflammatory process in multiple target organs such as the skin, gastrointestinal tract, and the airways supports the systemic nature of atopy. For infants with atopic dermatitis, allergen sensitization and the heightened Th2 response of the peripheral blood cells precedes the occurrence of clinical asthma; however, we currently do not know when the airway of the atopic infant becomes a target organ with inflammation and hyperresponsiveness, the phenotypic characteristics of asthma. In mice, epicutaneous allergen sensitization produces atopic dermatitis, as well as heightened airway reactivity. This finding has suggested that atopic dermatitis may not only precede asthma, but may also contribute to its development. If this also occurs in humans, then more aggressive treatment of atopic dermatitis in infants might minimize the development of asthma. Our understanding of the origins of asthma is limited. In order to design strategies for early intervention and prevention of this disease, it is critical to determine when the airway becomes a target organ and whether atopic infants have phenotypic characteristics of the asthmatic airway early in life. Specific Aim # 1: Evaluate whether infants with atopic dermatitis exhibit the phenotypic characteristics of the asthmatic airway. Airway reactivity and exhaled nitric oxide kinetics will be measured in infants with atopic dermatitis and healthy controls. Using cultured nasal airway epithelial cells from these infants, we will also evaluate the production of Th2 chemokines following stimulation of the cells with IL-4 and IL-13. Specific Aim # 2: Evaluate whether the presence of phenotypic characteristics of the asthmatic airway identifies infants and toddlers that develop clinical asthma by 5 years of age.