Inhibition of exercise-induced asthma by theophylline

Abstract

Although an association between exercise and provocation of asthma has been recognized for 300 yr, Jones et al., ’ pediatricians at Alder Hey Children’s Hospital in Liverpool, appear to have been the first to attempt to assess the effect of drugs as modulators of the exercise-induced bronchoconstriction phenomenon. Among the drugs they investigated was the choline salt of theophylline, a formulation that contains 64% anhydrous theophylline. In a single-dose study in which the subjects were administered anhydrous theophylline of the equivalent of between 4.5 and 5.8 mg/kg body weight several hours before exercise challenge, the postexercise fall in FEV, was completely or partially prevented in eight of nine subjects, and Jones et al. concluded that theophylline was protective against exercise-induced wheezing. In retrospect, it appears that the FEV, was measured before drug administration and not immediately before exercise and thus one does not know how much of the putative inhibition of exercise-induced asthma (EIA) was due to the bronchodilator effect of theophylline. Anderson et al.’ have emphasized the importance of measuring expiratory flow rate immediately before exercise so that the bronchodilating effect of the drug and its inhibitory effect on EIA can be considered separately. Nonetheless, in the study of Jones et al., the maximal FEV, after exercise was observed at a mean of 90 min after drug administration, which would coincide with the time of the peak serum theophylline concentration after administration of a rapidly absorbed product such as the one used. This was the first suggestion of a pharmacodynamic effect of theophylline in asthma. During the past decade there have been 10 additional studies2-” in which the efficacy of theophylline in the prevention of EIA has been investigated (Table I). While these studies are not strictly comparable because of a number of differences in experimental design and particularly in dose of theophylline, there are some generalizations that can be made. First, the results of these studies have uniformly shown that the-