To assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the preceding year of inclusion can decrease the exacerbation rate in the year of treatment.

COPD is characterized by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response.One of the hypothesis for persistent airway inflammation is that the presence of recurrent infections is responsible for this condition.

Macrolide antibiotics have a bacteriostatic as well as anti-inflammatory properties. This clinical trial will investigate whether maintenance treatment with macrolide antibiotics during 1 year in people with 3 or more exacerbations in the preceding year of inclusion can decrease the exacerbation rate in that same year of treatment.

Inclusion Criteria:

• Diagnosis of COPD according to GOLD criteria (FEV1/FVC<70%), classification into GOLD I (FEV1 70-100% predicted), GOLD II (FEV1 50-70% predicted), GOLD III (FEV1 30- 50% predicted) or GOLD IV (FEV1 ≤ 30% predicted)
• Age ≥ 18 years
• Three or more exacerbations of COPD in one year for which a course of prednisone and/or antibiotic therapy was started
• Clinically stable during 1 month. Patients have to be free of COPD exacerbation or respiratory tract infection within a month prior to involvement in the study and they should not have received a high dose of systemic glucocorticoids or antibiotics in this period
• Informed consent

Exclusion Criteria:

• Use of antibiotics or high dose of systemic steroids within a month prior to involvement in the study.
• Addition of inhalation steroids to the patient's therapy regimen, shortly before entering the study.
• Pregnant or lactating women.
• Allergy to macrolides.
• Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).
• Asthma, defined as episodic symptoms of airflow obstruction which is reversible with bronchodilators, assessed with lung function testing.
• Presence of a malignancy which is clinically active.
• Bronchiectasis.
• Malignancy of any kind for which the subject is under treatment or is being monitored as part of follow up after treatment.
• Heart failure.
• Use of drugs which can adversely interact with macrolides and for which therapeutic monitoring cannot be undertaken.