Deposition of terbutaline in the large or small airways: A single-center pilot study of ventilation-perfusion distributions and airway tone

Background: Beta₂-receptor agonists are used as bronchodilators and may influence gas exchange, leading to transient hypoxemia via hypoxic vasoconstriction.Objectives: This single-center pilot study assessed whether responses of gas-exchanging elements or airway tone would vary depending on where terbutaline sulfate, as an aerosol, a beta₂-receptor agonist commonly used by patients with asthma, is deposited in the airways. We also questioned whether identical doses of nebulized terbutaline would elicit different responses in airway tone after differential deposition.Methods: Terbutaline mixed with a solution of technetium 99m diethylenetriamine pentaacetic acid was nebulized and inhaled in different modes on 2 study days by patients with stable asthma. The aerosol was directed to either the large or small airway. To confirm that different deposition patterns were obtained while identical doses were given on the 2 study days, the deposition pattern and total count over the lungs were recorded by a gamma camera. Arterial oxygen tension (PaO₂), ventilation-perfusion (V_A/Q) distributions (by multiple inert-gas-elimination technique), and specific airway conductance (by body plethysmography) were studied before and after the inhalations.Results: Five patients (3 women, 2 men) aged 27 to 71 years (mean age, 39 years) were enrolled. An 8-fold difference in penetration index indicated major differences in the deposition pattern on the 2 study days. Despite the low statistical power of the study (45%) due to the low number of participating asthmatic patients, we found that (V_A/Q) inequality increased significantly (P < 0.05) after large-airway deposition but not after small-airway deposition. Preservation of normal or near-normal PaO₂ was noted in both series of experiments, even though increased (V_A/Q) mismatch occurred after terbutaline was deposited in the large airways. We also confirmed significant responses in airway tone after both sets of terbutaline administration (P < 0.05 for both), and no differences in bronchodilation due to deposition site were found, showing that the changes in airway tone after the 2 modes of administration occurred independently of changes in (V_A/Q) matching.Conclusions: Our results suggest that the deposition of terbutaline in the large airways tends to increase (V_A/Q) inequality and that bronchodilation occurs regardless of the deposition pattern.