THEOPHYLLINE ATTENUATION OF AIRWAY RESPONSES TO ALLERGEN - COMPARISONWITH CROMOLYN METERED-DOSE INHALER

Background: The purpose of this study was to compare the protection af forded by individualized doses of theophylline and a cromolyn meter ed -dose inhaler (MDI) during allergen challenge. Methods: The study desi gn was randomized, double-blind, and crossover: Responses to inhaled a llergen were measured in 16 subjects with allergic asthma (age range, 18 to 35 years) after. 7 days of treatment with either placebo, once d aily slow-release theophylline producing a mean +/- SD serum concentra tion of 16 +/- 5 mu g/ml during the late phase, or 2 mg of cromolyn ad ministered by MDI four times daily. Forced expiratory volume in 1 seco nd was measured at frequent intervals, and airway responsiveness to hi stamine was measured before and 3 hours after allergen challenge. Resu lts: The mean +/- SD maximum decrease in forced expiratory volume in 1 second during the late phase was 30% +/- 14% during placebo treatment , 16% +/- 13% during theophylline treatment, and 13% +/- 14% during cr omolyn treatment (placebo vs theophylline and cromolyn, p = 0.0001; th eophylline vs cromolyn, p = 0.1). The geometric mean fold increase in airway responsiveness was 3.0 +/- 1.7 during placebo treatment, 1.7 +/ - 1.7 during theophylline treatment, and 1.5 +/- 1.6 during cromolyn t reatment (placebo vs theophylline and cromolyn, p = 0.0001; theophylli ne vs cromolyn, p = 0.1). Conclusions: Theophylline, when administered once daily as a slow-release formulation, was as effective as cromoly n, administered four times daily through an MDI, in attenuating airway responses to inhaled allergen. The protection afforded by both treatm ents, however; was modest when compared with the results of similar st udies with inhaled corticosteroids or other cromolyn formulations that deliver more drug to the lungs than the MDI available in the United S tates.