Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH

Eligibility Criteria

• 1. Outpatients with COPD, defined as airflow limitation with post-bronchodilator obstruction on baseline visit spirometry, identified by FEV1/FVC \< 70% or \< the lower limit of normal (5th percentile of a normal population based on Global Lung Function Initiative reference equations), OR any emphysema on chest CT noted in a clinical radiology report confirmed by study investigator review.
• 2. Eligible subjects must have PH documented as follows:
• * Main Pulmonary Artery/Ascending Aorta (PA/A) diameter \> 1.0 on clinically available CT scans AND transthoracic outpatient echocardiography showing normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction. Previous CT scan within 12 months of enrollment and echocardiogram done within 3 months of enrollment.
• * outpatient echocardiography done within 3 months of enrollment demonstrating PA sys \> 40 mmHg AND normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction
• 1. have been using a contraceptive measure (an intrauterine device (IUD), a contraceptive implant, oral contraceptives, barrier methods, or abstinence)
• 2. have a male partner with a vasectomy
• 3. have a tubal ligation procedure or a medical diagnosis (such as infertility) or therapies/procedures that precludes pregnancy (such as cancer treatments or endometrial ablation)
• 4. are in a same-sex relationship
• 5. have a male partner not capable of fathering children because of congenital anomalies, other surgery, or medical treatment
• 3. Moderate or severe hepatic impairment (Child-Pugh B and C). 4. Severe renal insufficiency (GFR \<30 ml/min/1.73 m2) 5. Echocardiography showing greater than moderate aortic stenosis (aortic valve area \<1.0 cm2), greater than moderate mitral regurgitation, or diastolic dysfunction (Any two of the following: Average E/e' \>14, Septal e' velocity \< 7 or lateral e' velocity \<10, LA volume index \> 34 ml/m2). LVEF \< 50%.
• 6. Any acute or chronic impairment (other than dyspnea) that limits ability to comply with the study requirements.
• 7. Current unstable angina, myocardial infarction or stroke within 6 months. 8. Requirement for nitrate therapy for any clinical indication. 9. Active prescription for a PDE-5 inhibitor or other pulmonary vasodilator other than oxygen as a PH treatment.
• 10. History of retinal disorders including retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy or crowded optic disc noted on ophthalmology examinations recorded in CPRS.
• 11. Contraindications: PDE-5i allergy, penile anatomical deformations, sickle cell anemia, multiple myeloma, leukemia, bleeding disorders, active peptic ulcer disease, retinitis pigmentosa or other retinal disorders. In accordance with 38 USC 7332, this information will be kept confidential and will not be disclosed in presentations, publications, or any other dissemination of the study results, or to anyone outside of the IRB-approved study team.
• 12. Use of any of the following: rifampin, systemic anti-fungal azole agents, protease inhibitors, phenobarbitol, dilantin.
• 13. Pregnant, possibly pregnant by report, or breastfeeding women. 14. Pulmonary veno-occlusive disease 16. Hypoxia (reproducible ambulatory SaO2 \< 90% on supplemental oxygen at rest recorded by a health care provider over 1 week).
• 17. Diagnosis of Obstructive Sleep Apnea without a prescription for treatment. 18. Newly prescribed (less than 4 weeks duration) bronchodilator or diuretic therapy or new enrollment in pulmonary rehabilitation at the time of Screening.
• 19. Students, VA employees, persons with impaired decision making, illiterate and non-English speakers, and terminally ill patients.
• 20. Nonadherence to accepted GOLD guidelines for treatment of COPD. 21. COPD or CHF exacerbation within the past 4 weeks. 22. On-going therapy with doxazosin.