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Previous Volume 337:1412-1419 November 13, 1997 Number 20 Next

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ABSTRACT

Background Inhaled glucocorticoids and oral theophylline are widely used to treat asthma. We compared the benefits of adding theophylline to inhaled glucocorticoid with those of doubling the dose of inhaled glucocorticoid in patients with persistent symptoms despite the use of inhaled glucocorticoid.

Methods In a double-blind, placebo-controlled trial, we randomly assigned 62 patients to receive either 400 µg of inhaled budesonide (low-dose budesonide) with 250 or 375 mg of theophylline (depending on body weight) or 800 µg of inhaled budesonide (high-dose budesonide). All doses were given twice daily for three months. Lung function was measured serially, and patients kept records of peak expiratory flow, symptoms, and albuterol use. The effects of treatment on endogenous cortisol levels were also assessed.

Results Both treatments resulted in improvements in lung function that were sustained throughout the study. As compared with treatment with high-dose budesonide, treatment with low-dose budesonide plus theophylline resulted in greater improvements in forced vital capacity (P = 0.03) and forced expiratory volume in one second (P = 0.03). There were significant and similar reductions in ₂-agonist use and the variability of peak expiratory flow, a correlate of bronchial hyperresponsiveness and the severity of asthma. Serum cortisol concentrations were significantly reduced in the group given high-dose budesonide (from a mean [±SE] of 18.4±2.4 µg per deciliter to 15.9±2.1 µg per deciliter, P = 0.02) but were unchanged in the other group. The median serum theophylline concentration was 8.7 µg per milliliter (therapeutic range, 10 to 20) among those who received theophylline. Both treatments were well tolerated.

Conclusions For patients with moderate asthma and persistent symptoms, low-dose inhaled budesonide with theophylline and high-dose inhaled budesonide produced similar benefits. Effects were achieved at theophylline concentrations below the recommended therapeutic range. The addition of low-dose theophylline to inhaled glucocorticoid may be preferable to and cheaper than increasing the dose of inhaled glucocorticoid.

Source Information

From the Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London (D.J.E., D.A.T., K.F.C., B.J.O., P.J.B.); and the Division of Respiratory Medicine, Thoracic Clinics, Karolinska Institute, Stockholm, Sweden (O.Z.).

Address reprint requests to Dr. Barnes at the Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St., London SW3 6LY, United Kingdom.

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