Inhaled Treprostinil (Tyvaso Nebulizer) For COPD Patients With Hypoxemia

This is a single-arm, proof-of-concept study evaluating the effects of inhaled Treprostinil (Tyvaso nebulizer) on regional gas exchange and capillary blood oxygenation in patients with chronic obstructive pulmonary disease (COPD) and hypoxemia. The study will enroll 10 outpatient subjects aged ≥40 with a chronic bronchitis phenotype, confirmed COPD diagnosis, and a diffusing capacity of the lungs for carbon monoxide (DLCO) ≥45% predicted. All participants will receive inhaled Treprostinil via a 4-week dose titration protocol (starting at 3 breaths four times daily and increasing to 6 breaths as tolerated). The primary objectives are to "determine the effects of inhaled Treprostinil on regional gas exchange and capillary blood oxygenation as measured by hyperpolarized xenon-129 magnetic resonance imaging (HP129Xe MRI), including ventilation defect percentage (VDP), membrane defect percentage, red blood cell (RBC) transfer defect percentage and normalized RBC oscillation amplitude and RBC frequency shift," and to "determine whether pre-treatment VDP, membrane defect percentage, RBC transfer defect percentage, RBC chemical shift and normalized RBC oscillation amplitude predict a positive response to inhaled Treprostinil." Assessments will include HP129Xe MRI, spirometry with DLCO, 6-minute walk testing (6MWT), and echocardiography at baseline and after 4 weeks. Data will be analyzed for changes in regional lung function and oxygenation. Safety monitoring will focus on known adverse effects of inhaled Treprostinil including "cough, headache, hypotension, oropharyngeal pain, throat irritation and nausea," and will address more serious risks observed in the PERFECT trial (COPD exacerbation, respiratory failure, myocardial infarction, and death). By selecting subjects with DLCO ≥45% predicted and using a shorter 4-week treatment duration with titrated dosing, the study aims to mitigate these risks.