A COMPARISON OF LOW-DOSE INHALED BUDESONIDE PLUS THEOPHYLLINE AND HIGH-DOSE INHALED BUDESONIDE FOR MODERATE ASTHMA

Background Inhaled glucocorticoids and oral theophylline are widely us ed to treat asthma. We compared the benefits of adding theophylline to inhaled glucocorticoid with those of doubling the dose of inhaled glu cocorticoid in patients with persistent symptoms despite the use of in haled glucocorticoid. Methods In a double-blind, placebo-controlled tr ial, we randomly assigned 62 patients to receive either 400 mu g of in haled budesonide (low-dose budesonide) with 250 or 375 mg of theophyll ine (depending on body weight) or 800 mu g 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 treatmen t on endogenous cortisol levels were also assessed. Results Both treat ments resulted in improvements in lung function that were sustained th roughout the study. As compared with treatment with high-dose budesoni de, treatment with low-dose budesonide plus theophylline resulted in g reater improvements in forced vital capacity (P = 0.03) and forced exp iratory volume in one second (P = 0.03). There were significant and si milar reductions in beta(2)-agonist use and the variability of peak ex piratory flow, a correlate of bronchial hyperresponsiveness and the se verity of asthma. Serum cortisol concentrations were significantly red uced in the group given high-dose budesonide (from a mean [+/-SE] of 1 8.4 +/- 2.4 mu g per deciliter to 15.9 +/- 2.1 mu g per deciliter, P = 0.02) but were unchanged in the other group. The median serum theophy lline concentration was 8.7 mu g per milliliter (therapeutic range, 10 to 20) among those who received theophylline. Both treatments were we ll tolerated. Conclusions For patients with moderate asthma and persis tent symptoms, low-dose inhaled budesonide with theophylline and high- dose inhaled budesonide produced similar benefits. Effects were achiev ed at theophylline concentrations below the recommended therapeutic ra nge. The addition of low-dose theophylline to inhaled glucocorticoid m ay be preferable to and cheaper than increasing the dose of inhaled gl ucocorticoid. (C) 1997, Massachusetts Medical Society.