Non-invasive Ventilation System in Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD)

Inclusion Criteria: * Have participated and completed the NOVEL 1 or NOVEL 2 studies. * Be 21-80 years of age (inclusive) at time of informed consent. * Require nasal oxygen of ≥ 2 LPM during exertion, and ≥ 1 LPM at rest. * Exhibit dyspnea and have lung disease process dominated by COPD per the Study Investigator. * Have a self-reported MMRC Dyspnea Score ≥ 2 on a scale of 0-4. * Have spirometric evidence of COPD with an FEV1 of \< 50% predicted and FEV1/FVC \< 0.70, measured within the last 6 months (GOLD stage III and IV). * Have a resting respiratory rate of less than or equal to 30 bpm. * Be fluent in reading and speaking the English language. * Be able to clearly communicate and to indicate a self-assessment of dyspnea and/or fatigue. * Be willing and able to participate in, and to complete all required study procedures, including the ability to pull an E-sized oxygen cylinder. * Report having a smoking history of ≥ 10 pack-years. * Provide written informed consent to participate in the study. Exclusion Criteria: Subject must NOT meet any of the following criteria, or they will be excluded from study participation: * Be a current tobacco smoker * Have a history of pneumothorax in last 2 years. * Have a history of severe, giant bullae. * Have a history of unstable angina * Reports the onset of cardiac arrhythmia(s) within the past 7 days. * Report having serious epistaxis within the last 10 days. * Have a history of severe pulmonary hypertension and/or NYHA Stage III and IV decompensated heart failure. * Reports symptoms of acute COPD exacerbation within the past 48 hours. * Have been discharged from the hospital within 30 days of screening for infection or acute illness or COPD exacerbation. * Have a prescription or history of requiring \> 8 LPM oxygen during exertion. * Have a history of serious allergic airways disease (e.g., high eosinophil count or elevated IgE). * Report or have evidence of LVEF \< 30 % * Have a BMI \> 40 * Have a history of thoracotomy, sternotomy, major cardiopulmonary intervention (e.g., lung resection, open heart surgery), or any procedure 6 months before study entry likely to cause instability of pulmonary status. * Have a history of lung disease unrelated to smoking that affects oxygenation or survival. * Is participating in another intervention study or have participated within 90 days of enrollment. * Have endobronchial valves or other bronchial tree implants such as stents. * Have a disease or condition expected to cause death, inability to perform procedures for the trial, or inability to comply with the therapy. * Have a history of intolerance to oxygen therapy.