Specific antagonism of adenosine‐induced bronchoconstriction in asthma by oral theophylline.

Abstract

The airway response to increasing concentrations of inhaled adenosine and histamine after oral theophylline or matched placebo was studied in 9 asthmatic subjects. Changes in airway caliber were followed as sGaw [specific airways conductance] and FEV1 [forced expiratory volume in 1 s] and concentration-response curves constructed. Inhaled adenosine caused concentration-related bronchoconstriction and was 4-5 times less potent than inhaled histamine. Theophylline, which achieved a mean plasma level of 15.9 and 16.6 .mu.g/ml on the histamine and adenosine study days, respectively, caused significant increases in FEV1 (17%) and sGaw (41-53%) whereas placebo had no effect. Theophylline also protected the airways against histamine- and adenosine-induced bronchoconstriction. Theophylline had a greater protective effect against adenosine (concentration-ratio 17.4 for FEV1 and 12.8 for sGaw) than against histamine (concentration ratio 5.6 for FEV1 and 5.4 for sGaw (P < 0.05)). At therapeutic concentrations theophylline is a specific antagonist of the airway effects of adenosine in addition to being a bronchodilator and a functional antagonist.