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Long-term Erythromycin Therapy Is Associated with Decreased Chronic Obstructive Pulmonary Disease Exacerbations

¹ Department of Clinical Medical Sciences, St. Augustine Campus, University of the West Indies, St. Augustine, Trinidad and Tobago; and ² Academic Unit of Respiratory Medicine, University College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to J. A. Wedzicha, M.D., Academic Unit of Respiratory Medicine, Royal Free & University College Medical School, Rowland Hill Street, Hampstead, London NW3 2PF, UK. E-mail: j.a.wedzicha{at}medsch.ucl.ac.uk

Rationale: Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations.

Objectives: To determine whether regular therapy with macrolides reduces exacerbation frequency.

Methods: We performed a randomized, double-blind, placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months, with primary outcome variable being the number of moderate and/or severe exacerbations (treated with systemic steroids, treated with antibiotics, or hospitalized).

Measurements and Main Results: We randomized 109 outpatients: 69 (63%) males, 52 (48%) current smokers, mean (SD) age 67.2 (8.6) years, FEV₁ 1.32 (0.53) L, FEV₁% predicted 50 (18)%. Thirty-eight (35%) of the patients had three or more exacerbations in the year before recruitment, with no differences between treatment groups. There were a total of 206 moderate to severe exacerbations: 125 occurred in the placebo arm. Ten in the placebo group and nine in the macrolide group withdrew. Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 (95% confidence interval: 0.489, 0.859; P = 0.003) and that these patients had shorter duration exacerbations compared with placebo. There were no differences between the macrolide and placebo arms in terms of stable FEV₁, sputum IL-6, IL-8, myeloperoxidase, bacterial flora, serum C-reactive protein, or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period.

Conclusions: Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population.

Clinical trial registered with www.clinicaltrials.gov (NCT 00147667)

Key Words: FEV₁ • chronic obstructive pulmonary disease exacerbation • macrolide • exacerbation frequency

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations. What This Study Adds to the Field Macrolide therapy was associated with a significant reduction in COPD exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this patient population.

 

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