Effect of a short course of clarithromycin therapy on sputum production in patients with chronic airway hypersecretion

Study objective: Long-term administration of macrolide antibiotics reduces sputum production in patients with chronic airway diseases, probably by inhibiting airway inflammation. The objective of the present study was to determine the acute effects of a macrolide on airway chloride secretion and sputum production. Methods: We first investigated the effect of erythromycin treatment on chloride diffusion potential difference (CPD) across tracheal mucosa in vivo. Next, we conducted a double-blind, parallel-group study examining the effect of 7 days of treatment with clarithromycin (400 mg/d), amoxicillin (1,500 mg/d), or cefaclor (750 mg/d) in patients with chronic bronchitis or bronchiectasis without apparent respiratory infection. Results: IV administration of erythromycin decreased the CPD of rabbit tracheal mucosa in a dose-dependent manner. Treatment of patients with clarithromycin decreased sputum production, whereas amoxicillin and cefaclor treatment had no effect. The percentage of patients whose sputum decreased > 30% from baseline (responders) was 38% in the clarithromycin group, 7% in the amoxicillin group, and 0% in the cefaclor group. During treatment with clarithromycin, the sputum solid composition increased and chloride concentration decreased in responders, but these changes were not observed in nonresponders. Conclusion: Short-term administration of 14-membered macrolide reduces chronic airway hypersecretion, presumably by inhibiting chloride secretion and the resultant water secretion across the airway mucosa.