Effects of Theophylline on Inhaled Methacholine and Histamine in Asthmatic Children

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Abstract
The effects of a therapeutic serum theophylline concentration on inhaled methacholine and histamine were studied in 8 stable, moderately severe asthmatic children 8-15 yr of age. Placebo or theophylline in a hydroalcoholic solution was administered in a double-blind fashion, and standard histamine and methacholine challenges were performed following both placebo and theophylline. Serum theophylline concentration averaged 13 mg/l (range 4.0-22.1). Theophylline caused a significant increase (P < 0.01, paired t test) in provocative dose for a 20% drop in FEV1 [forced expiratory vol in 1 s] (PD20FEV1) for both methacholine (from a mean of 19.1 to 57.5) and histamine (75.9 to 144.5). This effect did not correlate with the small (7.6% increase in FEV1) but significant bronchodilatation produced by theophylline. Evidently, theophylline in doses that achieve serum concentrations in the usual therapeutic range produces significant attenuation of the bronchoconstrictor response to methacholine and histamine challenges in asthmatic children. The mechanism and therapeutic implications of this remain undefined.