Please select the eligibility criteria that correspond to the clinical trial below.
Title: Doxycycline and Airway Inflammation in COPD: A Randomised Placebo Controlled Trial Studying the Effects of Doxycycline on Airway Inflammation in Patients With Moderate and Severe Stable COPD.
Brief Summary: COPD is a progressive pulmonary disease that is characterized by an inflammatory process in the airways and the lungs which leads to progressive airway obstruction. The inflammation is associated with tissue loss and remodelling. The investigators hypothesized that doxycycline reduces neutrophilic airway inflammation in patients with COPD. Therefore the investigators will conduct a randomized trial of doxycycline in 30 patients.


Options:
A: Inclusion Criteria:

* Patients \> 40 years of age, in our outpatient clinic with chronic cough and COPD (gold2-4)
* Chronic cough is defined as a cough \> 12 weeks duration, at least 12 weeks a year in 2 subsequent years.
* Analysed for bronchiectasis prior to participation by CT-thorax.

Exclusion Criteria:

* Prior history of asthma
* Use of i.v. or oral corticosteroids and or antibiotics for an exacerbation 3 weeks before inclusion
* Patients suffering from other relevant lung diseases.
* Clinically relevant abnormal laboratory values suggesting an unknown disease requiring further clinical evaluation.
* Liver disease, (ALAT and/or ASAT levels two or more times the upper limit of normal).
* Pregnancy or lactation.
* Use of macrolides the last 6 weeks prior to inclusion.
* Allergy or intolerance to macrolides.
* Other research medication started 2 months prior to inclusion.
* Prior randomisation in this study.
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:

* 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.

Answer: D