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.

Inclusion criteria

• Outpatients of either gender, age ≥ 40.
• Clinical evidence of chronic bronchitis (a productive cough lasting more than 3 months within a 2-year period).
• Current or former cigarette smokers with a smoking history of 20 or more pack-years.
• Clinical diagnosis of chronic obstructive pulmonary disease (COPD) confirmed by spirometry demonstrating forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio < 0.70, pre-bronchodilator FEV1 ≥ 30% predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 45% predicted.
• On stable maintenance COPD medications including inhaled corticosteroids (ICS), long-acting beta agonists (LABA), long-acting muscarinic antagonists (LAMA), combination inhalers, azithromycin, or roflumilast (with no changes over the past 3 months).
• Patients with hypoxemia, evidenced by the use of supplemental oxygen at rest or during exercise (≤ 4 liters/minute).
• Willing and able to give informed consent and adhere to visit and protocol schedules (consent must be obtained prior to any study procedures).
• Women of childbearing potential must have a negative serum pregnancy test, confirmed prior to participation in this investigational protocol.

Exclusion criteria

• Upper respiratory tract infection within 6 weeks (participants may be rescreened after this period).
• History of lung resection surgery or pleural decortication.
• Previous history of pneumothorax.
• Imaging evidence of interstitial lung disease, occupational lung disease, or chronic infectious lung disease.
• History of asthma.
• History of exposure to occupational or environmental hazards known to cause lung disease.
• Positive pregnancy test for women of childbearing potential.
• Major chronic illness that, in the judgment of the study physician, would interfere with participation in the study.

For Magnetic Resonance Imaging (MRI):

• Contraindications to MRI based on screening questionnaire responses.
• Participant is pregnant or lactating.
• Respiratory illness of bacterial or viral etiology within 6 weeks prior to MRI.
• Known cardiac arrhythmia.
• Participant does not fit into the hyperpolarized xenon-129 (^129Xe) vest coil used for MRI.
• Participant cannot hold their breath for 10 seconds.
• Participant is unlikely to comply with instructions during imaging.