Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation.

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations.