Effect of alpha-adrenergic blockade on exercise-induced asthma and conditioned cold air

Cooling and drying of the intrapulmonary airways have been shown to be important stimuli for the development of bronchospasm induced by exercise and isocapnic cold air hyperventilation. It has also been suggested that alpha-adrenergic receptor activity is increased at lower temperatures. To evaluate the role of alpha-adrenergic activity in the development of bronchoconstriction during airway cooling, we examined the effects of alpha-adrenergic blockade with phentolamine on bronchospasm induced by exercise and isocapnic cold air hyperventilation in 8 asthmatics. Exercise consisted of 6 min of steady-state exercise at 90% predicted maximal heart rate breathing compressed air at 0% humidity and 21 ± 1° C (mean ± SD). During baseline exercise studies, FEV₁ fell 41.6 ± 15.8%, but only 12.8 ± 8.5% during alpha-adrenergic blockade (p < 0.001). Isocapnic cold air challenge consisted of breathing compressed cold air (0% humidity, -17 ± 4° C) for 3-min periods, with stepwise increases in minute ventilation (V̇E) until the FEV₁ fell at least 20%. During baseline cold air challenges, FEV₁ fell 20% (PD₂₀ FEV₁) at a V̇E of 48.8 ± 21 L/min. However, during alpha-adrenergic blockade 6 asthmatics were able to achieve much higher levels of V̇E (86.6 ± 22.7 L/min) before FEV₁ fell 20% (p < 0.01), and 2 asthmatics did not decrease their FEV₁ by 20%, despite reaching maximal levels of ventilation of 132 and 108 L/min, respectively. Alpha-adrenergic blockade did not affect airways responses to histamine or ragweed antigen (p > 0.1). These results suggest that alpha-adrenergic mechanisms may partially mediate airways reactivity to exercise and cold air hyperventilation, but do not affect airway responses to nonspecific pharmacologic or immunologic challenges. It would appear that exercise- and cold-air-induced bronchospasm are partially mediated by alpha-adrenergic mechanisms that are activated during airway cooling.