This prospective, randomised, double blind, multicentre, placebo controlled study examined the effect of ambroxol (an agent stimulating mucociliary clearance and surfactant production) in preventing acute exacerbations of COPD. 242 patients with GOLD stage IIa COPD, a history of chronic bronchitis, abnormal chest auscultation, and at least one exacerbation in the previous year were recruited and randomised to receive ambroxol or placebo for 12 months. An exacerbation was defined as the presence of purulent sputum with at least one of the following: temperature >38°C, general malaise, dyspnoea, difficult expectoration, or new systemic leucocytosis. There was no significant difference in the primary end point—the number of patients free from exacerbation—between the ambroxol and placebo groups at either 6 or 12 months (63% v 60% at 6 months, 56% v 53% at 12 months, respectively).

Systematic reviews have suggested a significant reduction in the number of exacerbations in patients with mild COPD and chronic bronchitis treated with mucolytic agents. These reviews included many studies using N-acetylcysteine. The AMETHIST trial shows the importance of examining the evidence for individual mucolytic drugs before prescription.