Asthma is the most common chronic respiratory disease of childhood with prevalence, morbidity and mortality increasing in epidemic proportions throughout the world despite better diagnosis and improved anti-inflammatory treatment. Recombinant humanized monoclonal anti-IgE is the most promising immunomodulatory agent available today to non-specifically modulate IgE, the major effector molecule in allergic asthma. Anti-IgE reduces free IgE and IgE receptors more than 95 percent, improves asthma symptoms, lung function, and reduces prn bronchodilator use and corticosteroid use in moderate to severe persistent allergic asthma in adolescents and adults. Proposed here are two projects, each prospective, randomized, masked, and placebo-controlled, to evaluate the effectiveness and safety of anti-IgE in primary and secondary asthma prevention in children. Proposal number 1 or primary asthma prevention will determine whether anti-IgE can prevent the development of asthma in 232 high-risk infants 1 to 2 years of age with atopic dermatitis, food allergy, or allergic rhinitis and specific IgE and a parental history of atopy. Patients will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo, and followed for the development of asthma for 3 years. Secondary objectives include determination if anti-IgE compared to placebo differ with respect to (1) the onset of at least mild persistent asthma, (2) lung impedance and bronchial responsiveness determined by impulse oscillation, (3) skin test reactivity and markers of inflammation, (4) effect on atopic disorders, and (5) long-term safety and growth. Proposal number 2 or secondary asthma prevention will determine the effectiveness of anti-IgE compared to placebo to reduce inhaled corticosteroid (ICS) requirements (steroid sparing) in 140 children 5-12 years of age with moderate to severe persistent allergic asthma requiring ICS. Subjects will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo for 1 year, and followed in two phases. During Phase I or the 12-week adjunctive phase, patients will maintain their stable dose of ICS, and during Phase II or the 40-week ICS withdrawal phase, subjects will have their ICS reduced according to protocol. The efficacy and safety of anti- IgE therapy versus placebo will be compared in terms of (1) the reduction in ICS dose measured by real time monitoring of ICS use electronically (primary aim), (2) asthma symptom scores, medication use, and peak expiratory flow levels monitored electronically, (3) levels of lung function and bronchial responsiveness, (4) humanistic and pharmacoeconomic measures, (6) skin test reactivity and markers of inflammation, (7) somatic growth, and (8) adverse events.
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