Lovastatin as a Potential Modulator of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)

The impact of lovastatin, 40mg by mouth once daily on biological and clinical outcomes will
be evaluated in an exploratory 16-week comparative treatment efficacy trial in 44 adult
former smokers with established COPD of moderate severity. This trial employs a longitudinal
randomized, parallel-arm, double-blind, placebo-controlled design using biomarkers of airway
inflammation as the primary outcomes of interest.

Inclusion Criteria:

1. Adult (≥45 years) former smokers with ≥ 10 pack-years of cigarette smoking

2. FEV1/FVC ratio < 70%

3. Post-bronchodilator FEV1 between 50% and 80% of predicted if undergoing bronchoscopy,
or between 30% and 80% of predicted if undergoing induced sputum only

4. DLco/VA < 80% predicted

5. Ability to perform and adhere to study protocol

6. ability to provide informed consent.

Exclusion Criteria:

1. Asthma or other comorbid lung disease,

2. Hypoxemia (PaO2 < 55 mmHg or SpO2 < 88% on room air), if undergoing bronchoscopy

3. Exacerbation of COPD within the last 6 weeks

4. Upper or lower respiratory tract infection within the last 6 weeks

5. Current smoking

6. Significant coronary artery disease as reflected by unstable angina, myocardial
infarction or angioplasty/stenting/bypass surgery within 6 months

7. Current use of HMG-coA-reductase inhibitors

8. Current use of inhaled corticosteroid

9. Concurrent use of other Cyp3A4 (isoform of cytochrome P450) inhibitors

10. History of adverse reaction to HMG-coA-reductase inhibitors (rhabdomyolysis,
hepatitis)

11. For patients undergoing bronchoscopy, any contraindication to fiberoptic bronchoscopy
or conscious sedation, including abnormalities of the platelet count, prothrombin
time or partial thromboplastin time.