Twice daily slow-release theophylline vs placebo for 'morning-dipping' in asthma

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