The goal of this clinical trial is to evaluate the impact of inhaled Treprostinil on breathlessness and low exercise capacity in patients living with mild chronic obstructive pulmonary disease. Participants will be asked to:

• Perform lung function and exercise tests
• Have ultrasound of their heart
• Have CT images of their lungs
• Visit the lab on 5 different occasions (plus one visit to the CT imaging clinic)

The researchers will compare the effectiveness and feasibility of inhaled Treprostinil to improve breathlessness upon exertion and exercise capacity

The study consists of 6 visits (5 to the Clinical Sciences Building at the University of Alberta):

Day 1: participants will provide informed consent, medical history and health screening (Physical activity readiness questionnaire [PAR-Q+], COPD assessment test [CAT], modified medical research council [mMRC], euro quality of life- 5 dimensions [EQ-5D]), be familiarized to the laboratory and experimental measurement protocols, conduct a pulmonary function test, and conduct an incremental CPET to determine peak oxygen consumption (V̇O2peak) on the cycle ergometer. Throughout exercise, non-invasive measurements of cardiac output (impedance cardiography), heart rate (electrocardiogram), expired gases (metabolic cart), and oxygen saturation (pulse oximetry) will be completed. A small blood sample will be collected via finger prick to measure hemoglobin (to correct DLCO - part of the pulmonary function test). Ratings of perceived breathing and leg discomfort (Borg scale), as well as dimensional descriptors of dyspnea scales will be recorded throughout the exercise test, and immediately upon exercise cessation.

Days 2-4: participants will complete resting, seated, DLCO maneuvers as well as a constant workload (75% of the peak power output determined from the CPET) cycling exercise test until volitional fatigue (i.e., exhaustion) with or without inhaled Treprostinil (placebo, 36, or 78 mcg; via Tyvaso® Inhalation Solution). DLCO and its components will be evaluated by standardized multiple breath-hold technique. A small blood sample will be collected via finger prick to measure hemoglobin for the DLCO maneuvers prior to and following exercise. Throughout exercise, non-invasive measurements of cardiac output (impedance cardiography), heart rate (electrocardiogram), expired gases (metabolic cart), and oxygen saturation (pulse oximetry) will be completed. Additionally, ratings of perceived breathing and leg discomfort (Borg scale), as well as dimensional descriptors of dyspnea scales will be recorded throughout the exercise test, and immediately upon exercise cessation. The drug condition (placebo, 36, or 78 mcg) will be randomized (block randomization) by a member of our research team who is not involved in data analysis or collection.

Day 5: participants will complete supine DLCO maneuvers (multiple breath-hold technique) as well as resting echocardiography (to measure pulmonary artery and cardiac function) with and without inhaled Treprostinil (placebo, 36, and 78 mcg). A small blood sample will be collected via finger prick to measure hemoglobin for the DLCO maneuvers.

Day 6: participants will undergo a low contrast CT scan of their chest for quantification of pulmonary vascular volumes (i.e., blood vessel volume in the lungs). No drug intervention will be completed on Day 6.

Inclusion Criteria:

• Patients with mild COPD (defined as having a postbronchodilator FEV1/FVC ratio <0.70 and FEV1 ≥ 80% predicted

Exclusion Criteria:

• Pre-existing heart failure and pulmonary artery hypertension.
• Known thrombocytopenia.
• Resting blood pressure of <90mmHg systolic and <50 mmHg diastolic.
• Known sensitivity to prostanoids
• Severe hepatic insufficiency