Theophylline in maintenance treatment of chronic asthma: concentration-dependent additional effect to beta 2-agonist...

The effect of long-term treatment with theophylline was studied in 20 chronic asthmatic patients receiving oral and inhaled beta 2-agonists. In a double-blind, randomized cross-over fashion during three consecutive 6-week periods, the patients received theophylline in individually adjusted dosages or placebo to obtain plasma concentrations of 25-45 mumol/l, 50-85 mumol/l and 0, respectively. PEF, beta 2-aerosol consumption, symptom scores and side-effects were recorded daily. The addition of theophylline caused a significant further bronchodilating effect. There was, however, a large interindividual variation in response to additional theophylline and only half of the subjects were responders. Those responding had increased therapeutic efficacy from a steady-state concentration in the range of 50-85 mumol/l compared to the lower concentration. The responders had, on average, more pronounced air-flow obstruction. The incidence of adverse reactions increased with increasing concentrations of theophylline.