Dose-response effects of atropine on thermal stimulus-response relationships in asthma

To determine how cholinergic blockade modifies the stimulus-response relationships to thermal provocations, we had seven asthmatics perform increasing levels of eucapnic hyperventilation of subfreezing air (-10.6 +/- 1.9 degrees C) after pretreatment with aerosols of saline and atropine in doses of 0.25, 0.5, 1.0, 3.0, and 6.0 mg. Testing was performed on 5 separate days with both placebo and a single dose of drug. In control experiments, increasing ventilation produced a progressive decrease in the 1-s forced expiratory volume in a stimulus-response fashion. There were no significant differences between any placebo study. Atropine pretreatment did not abolish the obstructive response to airway cooling at any dose but, rather, shifted the stimulus-response curve to the right, so that the effects of muscarinic blockade could be overcome by increasing the stimulus. There were no significant differences between the results observed with 0.25 or 6 mg of atropine. These data demonstrate that cholinergic mechanisms play, at best, a very minor role in exercise-induced bronchospasm and offer a unifying explanation for the disparate findings in the literature regarding antimuscarinic agents in this condition.