Twice daily slow‐release theophylline vs placebo for ‘morning‐dipping’ in asthma.

Abstract

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.