Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹
¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, Italy

Background: Use of short-acting ß₂-agonists in chronic obstructive pulmonary disease (COPD) during treatment with long-acting ß₂-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.
Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose) after a 1-week washout (baseline), 8 hours after the first administration of formoterol 12 µg (day 1), and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler). Peak expiratory flow, forced expiratory volume in one second (FEV₁), forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.
Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV₁, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV₁ dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001). Within each dose-response curve, FEV₁ was different only at baseline and at day 1 (P < 0.001), when FEV₁ was still greater at 800 µg than at 0 µg (P < 0.02). In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001), always being higher at 800 µg than at 0 µg (P < 0.05).
Conclusion: In patients with stable COPD, the maximal effect of salbutamol on peak expiratory flow, FEV₁, and forced vital capacity was unchanged after either acute or chronic treatment with formoterol. With increasing doses of salbutamol, FEV₁ increased only after acute administration of formoterol. Forced vital capacity also significantly improved during long-term treatment with formoterol.

Keywords: chronic obstructive pulmonary disease, salbutamol, formoterol, long-acting ß₂-agonists