TWICE DAILY SLOW-RELEASE THEOPHYLLINE VS PLACEBO FOR MORNING-DIPPING IN ASTHMA

The results of a double-blind control crossover trial of slow release theophylline Nuelin S.A. in improving symptoms of morning-dipping in 12 asthmatic patients are reported. Sleep disturbance was lessened and morning-dipping, though not abolished, was improved by 24% (P < 0.01). Mean peak expiratory flow-rate (PEFR) on waking was significantly higher on active drug (262 l/min vs. 226 l/min, P < 0.001) as were the evening PEFR (316 l/min vs. 285 l/min, P < 0.05). Of the 12 patients, 7 achieved 26% improvement in mean PEFR (P < 0.05) with plasma theophylline levels in the range 28-44 .mu.mol/l. The other 5 patients improved by 9% (P < 0.02) with levels in the range 55-66 .mu.mol/l. Mean plasma cAMP 4-6 h after theophylline was significantly higher than with placebo (27.0 nmol/l vs. 17.6 nmol/l, P < 0.05) but significant correlations between cAMP and theophylline levels, and cAMP and PEFR were not demonstrated. A total of 9 patients, 33% of those originally recruited for this study, withdrew prior to the double-blind phase because of unacceptable side-effects of theophylline, i.e., nausea and headache.