- Peebles R Jr.,
- Permutt S,
- Togias A
Purpose of the Study
To determine the degree to which β2-adrenergic receptor agonists can reverse the allergen-induced late reduction in lung function.
Seven allergic subjects with mild asthma.
In phase I of the study, terbutaline was administered as an initial bolus followed by continuous intravenous infusion over 45 minutes to determine the maximal attainable bronchodilation at baseline. In phase II, the subjects underwent an allergen inhalation (ragweed) challenge until forced expiratory volume in 1 second (FEV1) declined by at least 20%. Seven hours later, subjects were randomized and crossed over to receive terbutaline or a vehicle intravenous infusion identical to the phase I infusion protocol. Forced expiratory spirometry was performed at baseline and every hour after allergen-inhalation challenge. Spirometry was performed before and every 5 minutes through terbutaline (phase II and I) and placebo infusion (phase II) as well.
At baseline, there was no significant difference in FEV1 or forced vital capacity (FVC) between phase I and phase II. In phase I, terbutaline infusion led to significant improvement in FEV1compared with preinfusion value (P < .03). After ragweed bronchoprovocation FEV1 decreased <85% at any single timepoint between hour 4 and 7 postallergen inhalation. On the day placebo was infused 7 hours after allergen inhalation, FEV1 values did not change significantly compared with the preinfusion value (P > .2). In contrast, on the day terbutaline was infused, FEV1 was significantly higher than preinfusion (P < .02). The overall pattern of FVC was the same as for FEV1. The kinetic curves for bronchodilator response to terbutaline infusion in phase I and in phase II were superimposable, indicating that the terbutaline induced bronchodilation was driven by the same pharmacologic mechanism.
The late reduction in lung function caused by allergen inhalation challenge in asthmatic subjects is rapidly and almost completely reversible by an intravenous β2-adrenoreceptor agonist.
Most previous studies have demonstrated that inhaled β2-adrenoreceptor agonists are only partially effective in reversing allergen-inhaled late phase airway obstruction. Interestingly, the ability to reverse this type of airway obstruction appears to be significantly enhanced using an intravenous route for drug administration. These observations challenge the current dogma that the airway obstruction observed 4 to 8 hours after allergen challenge is mostly related to airway edema, inflammation, and mucus secretion as opposed to bronchial smooth muscle spasm. A third arm of the study in which equivalent doses of β-agonist were given by aerosol would have been helpful in determining what role drug delivery may have contributed to the observed results.