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Thus, having treatments that reduce dyspnea in COPD is important. Pulmonary hypertension (PH) is a common complication of COPD that is associated with severe dyspnea, more frequent COPD exacerbations, and increased mortality. Multiple causes of PH, including a reduction in bioavailable vasodilator nitric oxide (NO), are associated with COPD (COPD\u2010PH). Phosphodiesterase type\u20105 inhibitor (PDE5i) therapy restores NO signaling and improves hemodynamics and dyspnea in patients with Group 1 Pulmonary Arterial Hypertension, but has not been proven effective in COPD\u2010PH. In a prior study (ClinicalTrials. gov identifier: NCT01862536), we investigated effects of 12 months of oral PDE5i therapy with tadalafil on 6\u2010min walk distance (6MWD) in a multi\u2010center, randomized, placebo\u2010controlled trial funded by the Department of Veterans Affairs. While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient\u2010reported dyspnea and HRQL at 6 months. Because of the importance of mitigating dyspnea in COPD\u2010PH, we developed a new study protocol examining the effect of PDE\u20105i therapy in COPD\u2010PH, with a reduction in dyspnea the primary outcome. In the current study (NCT05937854), we will conduct a prospective, randomized, double\u2010blind, multi\u2010center clinical trial to evaluate the effects of 6 months of maximally tolerated therapy with tadalafil (target dose 40\u2009mg\/day) versus placebo on dyspnea, as measured by University of California San Diego Shortness of Breath Questionnaire.<\/jats:p>","DOI":"10.1002\/pul2.70167","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:35:09Z","timestamp":1759206909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Study Design and Rationale for The Breathe Easier With Tadalafil Therapy for Exercise\u2010Related Dyspnea in COPD\u2010PH (BETTER COPD\u2010PH)"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9167-0937","authenticated-orcid":false,"given":"Elena","family":"DeSanti","sequence":"first","affiliation":[{"name":"VA Providence 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