Effect of antiasthma drugs on asthmatic reactions induced by toluene diisocyanate in sensitized subjects

Abstract

To determine the effect of antiasthma drugs on asthmatic reactions and airway inflammation, we studied several groups of sensitized subjects treated with active drugs or placebo before and after exposure to toluene diisocyanate in the laboratory. We observed that the steroidal anti-inflammatory agent prednisone, but not the nonsteroidal anti-inflammatory agent indomethacin, inhibits the late (but not the early) asthmatic reactions induced by TDI. Prednisone also inhibits the increase of bronchial responsiveness and the increase of neutrophils, eosinophils, and albumin in bronchoalveolar lavage fluid that are associated with late asthmatic reactions induced by exposure to TDI. Beclomethasone has a dose-dependent inhibitory effect on TDI-induced late asthmatic reactions, whereas theophylline has a partial inhibitory effect on both early and late asthmatic reactions, and verapamil, ketotifen, cromolyn. Beta 2-adrenergic agonists have variable effects: salbutamol has no effect on early and late asthmatic reactions by itself, but it potentiates the inhibitory effect of low doses of beclomethasone. Broxaterol inhibits early asthmatic reactions, but has no effect on the late asthmatic reactions and the associated inflammatory response. These results suggest that, in sensitized subjects, late asthmatic reactions induced by toluene diisocyanate can be prevented by steroidal anti-inflammatory agents, whereas early asthmatic reactions may be prevented either by an association of inhaled steroids and beta-adrenergic agonists, or by beta-adrenergic agonists (e.g., broxaterol) with more complex mechanisms of action.