Effect of ipratropium bromide and/or sodium cromoglycatepretreatment on water-induced bronchoconstriction in asthma

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 μg), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebocontrolled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean %±SD) was observed at 90 min: 63±28% and 58±22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36±19%, -42±19%, -49±18%, -56±15% mean %±SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5±23% NS) and significantly reduced the effect of 4 (-15±22%), 8 (-21±20%) and 16 ml (-24±18%) water. Ipratropium bromide caused a weaker but significant attenuation; fall in sGaw was -15±15%, -18±19%, -30±21% and -41±27% with 2, 4, 8 and 16 ml water respectively. Treatment with both drugs prevented UMDW bronchoconstriction; a decrease in sGaw greater than 10% was observed in four subjects only. These results suggest that water-induced bronchoconstriction is determined by more than one mechanism