Effect of theophylline on airway responses to inhaled platelet-activating factor in man

Abstract

It has been suggested that theophylline may possess anti-inflammatory actions which underlie its antiasthmatic properties. We examined whether theophylline could inhibit the bronchoconstriction and the bronchial hyperresponsiveness induced by inhaled platelet-activating factor (PAF) in eight nonasthmatic subjects in a double-blind, cross-over study. After oral theophylline (6 mg·kg-1), plasma theophylline at 1 h was 10.4 ± 1.8 mg·ml-1 (mean ± SEM) compared to 0.39 ± 0.19 mg·ml-1 on the placebo day (p < 0.005). PAF, inhaled in five successive doses every 15 min, caused a 56 ± 11% fall in V̇p30 (flow at 30% of vital capacity from a partial expiratory manoeuvre) after the first dose at 5 min, and diminishing responses with successive doses. Theophylline had no significant effect on PAF-induced bronchoconstriction. PAF caused a significant decrease in PC40 (the concentration of methacholine needed to cause 40% fall in baseline V̇p30) from a baseline of 12.8 mg·ml-1 (geometric standard error of mean (GSEM) 1.98) to 7.9 (1.79) mg·ml-1 on day 3 and 6.9 (1.74) on day 7 (p < 0.02). There was no significant difference when mean PC40 values on corresponding days after PAF were compared between placebo and theophylline treatment periods. Our results suggest that theophylline has negligible influence on the airway effects of PAF.