The Effect of Theophylline on Methacholine and Exercise-Induced Bronchoconstriction in Asthmatic Children

Abstract

The aim of the study was to investigate the effect of theophylline on bronchial hyper-responsiveness evaluated with exercise and methacholine challenge. Sixteen children with asthma were studied on 6 different days. On the first 2 days, baseline methacholine bronchoprovocation and exercise tests were performed. The children were randomly given a supply of active or placebo Theo-dur medication for 2 weeks in two divided doses of 16 to 24 mg/kg/day at 8 am and 8 pm. A second methacholine challenge was performed again after 10 days of treatment at 8 am, and the following day at the same time an exercise test was performed. A third methacholine challenge was performed on the 13th day of treatment at 12 noon, and the following day at the same time a third exercise test was performed. In the active treated group, PC₂₀ FEV₁ was significantly increased over baseline value both when the test was performed at 8 am (14.32 ± 10.16 mg/ml) (p < 0.002) and when the challenge was performed at 12 noon (17.31 ± 9.21 mg/ml) (p < 0.002). There was no significant change in the PC₂₀ FEV₁ in the placebo treated group. In the theophylline treated group the FEV₁ percentage fall during exercise-induced asthma (EIA) was significantly lower compared to baseline when the test was performed both at 8 am (delta FEV₁ 19.2% ± 13.93, p < 0.04) and at noon (delta FEV₁ 16.8% ± 12.2, p < 0.002). In the placebo group, there were no significant differences in the degree of EIA between baseline, morning, and noon tests. In the active treated group, there was a good correlation (r = -0.77, p < 0.01) between the severity of methacholine (PC₂₀ FEV₁) and exercise-induced bronchoconstriction (delta FEV₁%) in the baseline tests and no correlation at 8 am (r = 0.17, p > 0.1) and at 12 noon (r = 0.16, p > 0.1). In the placebo treated group, the correlation was significant at baseline, at 8 am, and at 12 noon. Theophylline immediately reduces airways responsiveness, and the response may differ in the same patient according to different stimuli.