A double-blind, placebo-controlled comparison of the efficacy of standard and individually titrated doses of theophylline in patients with chronic asthma.

Forty adult patients with chronic asthma completed a 3-month double-blind crossover study to compare the effect of sustained-release theophylline given both as a fixed 300 mg twice daily dose (standard) and an individually titrated dose (titrated) with placebo. Theophylline was given in addition to other usual therapy, inhaled bronchodilators, inhaled steroids and, in 12 patients, oral steroids. The 3-month period was preceded by a run-in phase to determine the dose of theophylline which each subject required to achieve peak serum levels of 12-20 mg/litre and trough levels of 8-12 mg/litre. Doses ranged from 300 mg to 700 mg twice daily. Twenty-one patients needed more than the standard dose to achieve satisfactory serum levels. Patients recorded daily peak flow rates and symptom scores and were seen at monthly intervals to measure lung function, check serum theophylline levels and change treatments, which were given in random order. FEV1 was significantly higher for the whole group after standard (2.11 litres) and titrated (2.15 litres) theophylline therapy than after placebo (1.89 litres), as was FVC, but in the large subgroup whose titrated dose was greater than the standard dose, the FEV1 only improved with the titrated dose. Peak flow measurements at home showed the same pattern. Patients taking oral steroids appeared to derive less benefit from theophylline than others. It is concluded that theophylline can usefully be added as a third-line drug in chronic asthma, but that since half the patients are likely only to benefit from a dose greater than 300 mg twice daily, while the other half may have high serum levels above this dose, it is essential to measure serum levels in order to use the drug effectively and safely.

Topical sodium cromoglycate in the management of atopic eczema--a controlled trial.

A double-blind, group comparison trial of a topical cream containing 4% sodium cromoglycate (SCG) was undertaken in forty-six patients with chronic atopic eczema. A statistically significant improvement was seen after 9 weeks in the actively treated patients compared with the placebo group. However, in general, no benefit was observed in severe eczema, perhaps due in some part to the seemingly late onset of action of SCG. Measurement of total serum IgE before and after the trial showed an increase in levels which was apparently unrelated to treatment with SCG or placebo or to a change in severity of the eczema. The amount of SCG in the urine was small and very variable, indicating low percutaneous absorption. The calculated bioavailability ranged from 0.01% to 2.75% of the applied dose. These results together with follow-up studies suggest that topical SCG as a long-term measure may be useful in the management of mild or moderately severe eczema, reducing the frequency of acute exacerbations.