Anti-Platelets in Chronic Obstructive Pulmonary Disease

This is a 6 week crossover study in current and former smokers with and without COPD to evaluate whether 2 weeks of dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs measured on a contrast CT scan) compared to placebo.

This is a single-center Phase IIa randomized double-blind crossover study in smokers with and without chronic obstructive pulmonary disease (COPD) to test whether dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs) compared to placebo.

We will enroll 30 subjects (20 with COPD, 10 without) who will each take part for 6 weeks. Participants and researchers will be blinded, they will not know which medications they are on first. Each participant will be asked to take aspirin and clopidogrel together for 2 weeks and also matching placebos for 2 weeks, with a 2 week washout period in between. Pulmonary blood flow will be evaluated with a contrast-enhanced CT scan of the chest two times over the 6 week study.

Eligibility Criteria:
Inclusion Criteria - COPD Cases:

* COPD (FEV1/FVC \< 0.7, FVC \>= LLN), GOLD Stage I/II/III (FEV1 \>= 40%)
* Current or former smoker of at least 10 pack years

Inclusion Criteria - Controls:

* Normal lung function (FEV1/FVC \>= 0.7, FEV1 and FVC \>= LLN)
* Current or former smoker of at least 10 pack years

Exclusion Criteria:

* Platelet count \< 150,000/dL or self-report of a bleeding disorder;
* Regular use of aspirin, clopidogrel or another antiplatelet medication;
* Allergy to aspirin, clopidogrel, albuterol or iodine/IV contrast;
* BMI \> 35;
* History of intracranial hemorrhage, severe GI bleed or other life-threatening bleed;
* Use of blood thinner (e.g. warfarin, lovenox or novel oral anti-coagulants);
* Continuous use of supplemental oxygen at home;
* Regular use of an NSAID;
* Daily use of oral steroids, theophylline, roflumilast, or loop diuretics;
* History of organ transplant or autoimmune disease on systemic therapy (rheumatoid arthritis, lupus);
* Use of a biologic medication with regular injections;
* Other current lung disease (interstitial lung disease, idiopathic pulmonary fibrosis, asthma);
* IV drug use within the last year;
* History of lung surgery to remove part of the lung;
* Known bullae or advanced destructive emphysema in more than 1/3 of the lungs;
* Treatment for cancer (systemic therapy or surgical/radiation within the thorax) in the last 12 months;
* Known diagnosis of pulmonary hypertension;
* Known systolic heart failure (RV or LV EF \< 40%);
* Acute or chronic renal insufficiency (estimated glomerular filtration rate \[GFR\] \<60 mL/min/1.73 m2 or self-report). GFR will be calculated using the CKD-EPI equation;
* Current or planned pregnancy in the next year;
* Regular marijuana smoking;
* Exacerbation of respiratory symptoms within the previous 6 weeks, such as that requiring hospitalization, oral prednisone or antibiotics to control symptoms, or longer and not yet returned to baseline; and
* Chest, abdominal or eye surgery, or a heart attack or stroke, within the last 3 months.