Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine

We undertook a study to determine whether inhalation of atropine could inhibit cold air-induced bronchoconstriction in a dose-dependent fashion. In seven subjects with asthma we assessed the effects of placebo and of various doses of inhaled atropine (0.13-2.08 mg) on base-line specific airway resistance (sRaw) and on the increase in sRaw produced by 5 min of voluntary eucapnic hyperventilation with subfreezing air at -17°C. We also assessed the effect of the lowest doses of atropine on the increase in sRaw produced by five breaths of 1.0% methacholine. Atropine in doses of 0.13 or 0.26 mg caused a maximal reduction in base-line sRaw and completely inhibited the effect of 1.0% methacholine on sRaw, but it did not inhibit the bronchomotor response to cold air. Higher doses of atropine did inhibit the effect of cold air on sRaw in a dose-dependent fashion. The dose of atropine required to inhibit this effect of cold air varied with the increase in sRaw produced by cold air after placebo. These results suggest that cold air causes bronchoconstriction through vagal pathways and that higher doses of antimuscarinic agents are required to inhibit vagally mediated bronchoconstriction than those required to reduce base-line airway tone or inhibit the effects of a large dose of an inhaled muscarinic agonist.