Please select the eligibility criteria that correspond to the clinical trial below.
Title: Influence of Macrolide Maintenance Therapy and Bacterial Colonisation on Exacerbation Frequency and Progression of COPD, a Randomized Double-blind Placebo-controlled Trial
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* GOLD II or III COPD (GOLD II: FEV1/FVC \< 70%; 50% \< FEV1 \< 80% predicted, GOLD III: FEV1/FVC \< 70%; 30% \< FEV1 \< 50% predicted ).
* Stable disease (no exacerbations in the last 3 months).
* Age \> 40 yrs.
* Written informed consent.

Exclusion Criteria:

* Infections and/or use of antibiotics in the last month.
* Bacterial colonization of the airways, proven by sputum cultures or broncho-alveolar lavage (BAL).
* Allergy for tetracyclines or a history of substantial side-effects.
* Active respiratory diseases other than COPD (e.g. sarcoidosis, tuberculosis, lung cancer, bronchiectasis).
* Acute exacerbation of COPD as defined by Anthonisen et al. \[10\].
* Signs and/or symptoms of a current respiratory or non-respiratory infection.
* Use of oral or intravenous corticosteroids or other immunosuppressive drugs within the last month.
B: * Key Inclusion Criteria: List primary criteria for study inclusion (i.e. do not need to enter entire list of inclusion criteria).

  1. Patient must be 50 years old or older.
  2. Patient must have a smoking history of at least 20 pack-years
  3. Patient must have stable COPD, GOLD 0, I and/or IIA.
  4. CT of chest with evidence of emphysema
* Key Exclusion Criteria: List primary criteria for study exclusion (i.e. do not need to enter entire list of inclusion criteria).

  1. FEV1 \< 70%.
  2. Exacerbations (defined as use of oral steroids or antibiotics) in the previous month.
  3. Cardiovascular Disease defined as abnormal EKG, known or suspected coronary artery disease or congestive heart failure.
  4. Diabetes mellitus
  5. Renal disease
  6. Liver disease
  7. Lung cancer
  8. ETOH use of more than \>6 beers \>4 mixed drinks daily
C: Inclusion Criteria:

* Age \> 45 years Tracheotomy History of COPD demonstrated by pulmonary function tests Informed Consent

Exclusion Criteria:

* Allergy to macrolides Life expectancy \< 1 year
D: 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.

Answer: D