Effect of theophylline on airway responsiveness to methacholine and on exercise-induced bronchoconstriction

The aim of this study was to compare the relative effect of (1) a single dose of a rapid release theophylline, (2) treatment for 1 week with a sustained release theophylline, and (3) placebo after a washout period of at least 2 weeks on bronchial hyperresponsiveness to methacholine and on exercise-induced bronchoconstriction in 14 mildly asthmatic children. A dose of rapid release theophylline increased geometric mean (GM) PC20 (mg/mL) for methacholine from 0.25 to 0.85 (P < .001) at a mean (+/- SD) serum theophylline concentration of 9.5 +/- 2.5 mg/L (52.3 +/- 14.24 mumol/L). After 1 week on a slow release theophylline, GM PC20 increased to 0.41 (P < .01) at a mean serum theophylline concentration of 13.63 +/- 4.7 mg/L (74.9 +/- 25.8 mumol/L), (P < .01) compared with rapid release theophylline. The difference in PC20 between both theophylline treatments was statistically significant (P < .05). No significant changes in PC20 were noted after placebo compared with baseline values. During baseline and after placebo mean maximum FEV1 fall (MMFF) after exercise was 40 +/- 19.9% and 31.7 +/- 15.5%, respectively (n.s.). After a dose of rapid release theophylline, MMFF on exercise test was 8.7 +/- 8.2% (mean serum theophylline concentration 10 +/- 3.2 mg/L (55.4 +/- 17.82 mumol/L)), P < .001 compared with baseline and placebo. After 1 week of treatment with slow release theophylline, MMFF was 26.2% +/- 18.3 (mean serum theophylline concentration 12.2 +/- 3.9 mg/L (67.43 +/- 21.5 mumol/L)) (P = .01 and P = .30 compared with baseline and placebo, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)