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Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations.

Abstract

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).

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  • Authors+Show Affiliations

    ,

    Department of Clinical Medical Sciences, St. Augustine Campus, University of the West Indies, St. Augustine, Trinidad and Tobago.

    , , , ,

    Source

    MeSH

    Aged
    Antibiotic Prophylaxis
    Double-Blind Method
    Erythromycin
    Female
    Forced Expiratory Volume
    Humans
    Inflammation
    Kaplan-Meier Estimate
    Macrolides
    Male
    Middle Aged
    Pulmonary Disease, Chronic Obstructive
    Sputum

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18723437

    Citation

    Seemungal, Terence A R., et al. "Long-term Erythromycin Therapy Is Associated With Decreased Chronic Obstructive Pulmonary Disease Exacerbations." American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 11, 2008, pp. 1139-47.
    Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178(11):1139-47.
    Seemungal, T. A., Wilkinson, T. M., Hurst, J. R., Perera, W. R., Sapsford, R. J., & Wedzicha, J. A. (2008). Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. American Journal of Respiratory and Critical Care Medicine, 178(11), pp. 1139-47. doi:10.1164/rccm.200801-145OC.
    Seemungal TA, et al. Long-term Erythromycin Therapy Is Associated With Decreased Chronic Obstructive Pulmonary Disease Exacerbations. Am J Respir Crit Care Med. 2008 Dec 1;178(11):1139-47. PubMed PMID: 18723437.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. AU - Seemungal,Terence A R, AU - Wilkinson,Tom M A, AU - Hurst,John R, AU - Perera,Wayomi R, AU - Sapsford,Ray J, AU - Wedzicha,Jadwiga A, Y1 - 2008/08/21/ PY - 2008/8/30/pubmed PY - 2008/12/18/medline PY - 2008/8/30/entrez SP - 1139 EP - 47 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 178 IS - 11 N2 - 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). SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/18723437/Long_term_erythromycin_therapy_is_associated_with_decreased_chronic_obstructive_pulmonary_disease_exacerbations_ L2 - http://www.atsjournals.org/doi/full/10.1164/rccm.200801-145OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -