Interaction of cromolyn and a muscarinic antagonist in inhibiting bronchial reactivity to sulfur dioxide and to eucapnic hyperpnea alone.

Abstract

To determine whether the combination of an agent thought to inhibit mediator release (cromolyn) and an agent that inhibits parasympathetic pathways inhibits sulfur dioxide-induced bronchoconstriction more than either agent alone, we measured the bronchomotor response of 9 asthmatic subjects to inhalation of sulfur dioxide after treatment with cromolyn sodium (200 mg by spinhaler), with atropine sulfate (2.0 mg by nebulizer), and with the 2 drugs given together. Then, to determine whether the combination of cromolyn and a parasympathetic antagonist would similarly inhibit bronchoconstriction provoked by a different nonallergic stimulus, we measured the bronchomotor response of another group of asthmatic subjects to eucapnic hyperpnea of dry air at room temperature after treatment with cromolyn (200 mg), with ipratropium bromide (100 and 200 micrograms by metered-dose inhaler), and with cromolyn (200 mg) and ipratropium bromide (200 micrograms) given together. In both studies, we found that the combination treatment provided greater protection than that obtained with either agent alone. The concentration of sulfur dioxide required to cause bronchoconstriction was significantly greater after treatment with the combination of cromolyn and atropine (2.58 ppm, geometric mean) than after cromolyn alone (0.84 ppm), after atropine alone (0.78 ppm), or after placebo (0.43 ppm). Similarly, the rate of ventilation with dry air required to cause bronchoconstriction was significantly greater after treatment with the combination of cromolyn and ipratropium (106 +/- 22 L/min, mean +/- SD) than after cromolyn alone (65 +/- 19 L/min), after 200 micrograms of ipratropium alone (64 +/- 13 L/min), or after placebo (43 +/- 10 L/min).(ABSTRACT TRUNCATED AT 250 WORDS)