Chronic treatment with indacaterol and airway response to salbutamol in stable COPD

Abstract

Tolerance to both the bronchoprotective effect, and, to a lesser extent, the bronchodilator activity, occurs with all inhaled β2-agonists. Assumed the importance of this topic and the lack of a clinical evaluation specifically designed to assess the impact of chronic administration of indacaterol on the response to salbutamol, we sought to compare the effect of 4-week treatment with indacaterol 150 μg once-daily versus formoterol 12 μg twice-daily on the dose-response curve to inhaled salbutamol (total cumulative dose of 800 μg) in a non-double-blinded, crossover, randomised, and controlled pilot trial that enrolled 20 outpatients with moderate to severe COPD. At the end of 4-week treatments, there was not a statistically significant difference between the two trough FEV1 (p = 0.16), and both indacaterol and formoterol were able to produce a significant (p < 0.001) increase in FEV1 mean differences (L) = indacaterol 0.15 (95% confidence interval (CI) 0.12-0.18); formoterol 0.10, (95% CI 0.08-0.12) 2 h after their inhalation. Salbutamol elicited an evident dose-dependent increase in FEV1 and this occurred also after regular treatment with indacaterol and formoterol with a further mean maximum increase of 0.10L (95% CI 0.05-0.14) and 0.05L (95% CI 0.02-0.08), respectively. The differences between indacaterol and formoterol in FEV1 increases after salbutamol were never statistically significant. The results of this study support the use of salbutamol as rescue medication for rapid relief of bronchospasm in patients suffering from COPD, even when they are under regular treatment with indacaterol.