Asthma is a chronic inflammatory disease of the airways. Monocytes-macrophages are activated and produce increased amounts of inflammatory cytokines in asthmatics when compared to normals. AMs from asthmatics express increased amounts of the low affinity IgE (CD23) receptor. IgE dependent activation of the CD23 receptor on macrophages induces the production of several inflammatory cytokines, including Interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-a) as well as nitric oxide (NO) and cyclic AMP (cAMP). The increased exhaled NO seen in asthmatics is most likely due to enhanced production in epithelial cells and the AM. The investigators hypothesize that the higher percentage of CD23 positive AMs in asthmatics is a marker of AM activation with increased responsiveness to IgE-dependent stimulation. Ligation of this CD23 receptor enhances NFkB, resulting in cytokine production and, either directly or indirectly, increases in NO production. They propose to determine the relationships between IgE complex stimulation of the CD23 positive AMs to increases in NFkB activity and inflammatory cytokine production. They will then determine that the elevated AM CD23 expression and levels of NFkB are markers of inflammation that correlate with exhaled NO measurements, symptom scores, and methacholine challenge in asthmatics when compared to normals. These studies will relate markers of lung inflammation on a cellular level to exhaled NO, a measure of inflammation in the lung. Finding non-invasive ways to monitor the chronic inflammatory process in asthma could then be applied to subsets of asthmatics where CD23 receptor expression may be involved, such as populations exposed to allergen or environmental endotoxin, to identify inflammation and ultimately impact on therapy. For example, if evidence of ongoing inflammation could be documented, then earlier initiation of anti- inflammatory therapy could be instituted in disease modification strategies.
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