Effects of the Breathe Technologies Ventilation System in Subjects With Chronic Obstructive Pulmonary Disease

• Logarithmic EMG amplitudes [ Time Frame: Study day 2 ] [ Designated as safety issue: No ]
  Surrogate for respiratory muscle work. Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Tidal volume [ Time Frame: Study day 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Thoracic to abdominal synchrony, as measured by respiratory inductance plethysmography. [ Time Frame: Study day 1,2 and 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen. Data will be collected electronically on an exercise data collection system.

• SpO2 and TcPCO2 [ Time Frame: Study day 1,2 and 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Pulmonary ventilation and carbon dioxide output at iso-time (the time of termination in the shortest constant work rate test for each subject) [ Time Frame: Study day 1,2 and 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Exercise duration for constant work rate exercise tests [ Time Frame: Study day 1,2 and 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Patient dyspnea and comfort scores [ Time Frame: Study day 1,2 and 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Arterialized hand-vein PCO2, and pH [ Time Frame: Study day 3 ] [ Designated as safety issue: No ]
  Mean differences with and without use of the BT-NIOV™ system and, with and without the use of supplemental oxygen.
• Exhaled gas measurements [ Time Frame: Study day 3 ] [ Designated as safety issue: No ]

  The following data will be collected electronically.

  • Minute ventilation
  • Dead space to tidal volume ratio
  • Dead space
  • CO2 output

Pilot study in 10 stable male subjects with severe-to-very severe Chronic Obstructive Pulmonary Disease (COPD) to evaluate the effects of short term use of the Breathe Technologies ventilation system on respiratory mechanics during constant work rate exercise in subjects with severe COPD. Two healthy male control subjects will also be evaluated in orde to validate the data collection system.

Subjects will participate in randomized partially blinded series of exercises at their constant work rate while using the Breathe Technologies ventilation system. Subjects will be assessed for pulmonary mechanics and gas exchange during constant work rate exercise as reflected by changes in the log amplitude of respiratory muscle EMG (intercostal, scalene and diaphragm) and chest wall to abdominal synchrony as measured by respiratory inductance plethysmography. Two healthy male control subjects will be evaluated in order to validate the data collection system. The exercises will take place over 3-4 visits with each visit lasting approximately 5 hours. Subjects may discontinue study participation at any time.

• Experimental: NIOV - Room air
  Intervention: Device: Breathe Technologies Noninvasive Open Ventilation (NIOV™) System
• Experimental: NIOV - Oxygen
  Intervention: Device: Breathe Technologies Noninvasive Open Ventilation (NIOV™) System
• Active Comparator: Oxygen Nasal Cannula
  Intervention: Device: Breathe Technologies Noninvasive Open Ventilation (NIOV™) System
• No treatment
  Control
  Intervention: Device: Breathe Technologies Noninvasive Open Ventilation (NIOV™) System

Inclusion Criteria for Healthy Subjects

• Adult males, ≥ 18 years of age at screening
• Currently in good general health as assessed by medical history and cardiopulmonary physical examination
• Willingness and ability to perform all study related procedures and tasks
• Ability to be properly fitted with the Breathe nasal mask
• Ability to use the Breathe ventilator system
• Ability to be properly fitted with an exercise mask
• Fluency in written and spoken English
• Provision of written informed consent

Inclusion Criteria for Subjects with COPD

• Adult males, ≥ 40 years of age
• Diagnosis of severe COPD (GOLD stage III or IV) defined as having a FEV1 < 50% of predicted and an FEV1/FVC ratio < 70% of predicted
• Ventilatory limitation to exercise, documented by a VE/MVV > 0.85
• SpO2 between 80% and 88% during incremental exercise testing on room air
• Willingness and ability (after training) to exercise on a cycle ergometer
• Willingness and ability to perform all other study related procedures and tasks
• Ability to be properly fitted with the Breathe nasal mask
• Ability to tolerate and be appropriately titrated on the Breathe ventilator (See Appendix E)
• Ability to be properly fitted with an exercise mask
• Fluency in written and spoken English
• Provision of written informed consent

Exclusion Criteria for Healthy Subjects

• History of chronic illness or medical condition(s) that in the opinion of the Principal Investigator makes the subject unsuitable for study participation
• Use of prescription medication(s) 30 days prior to screening, except as approved by the Principal Investigator
• Musculoskeletal or other non-pulmonary impairment that limits exercise tolerance
• Current participation in another interventional study or participation within 14 days of screening
• Presence of any condition or abnormality that in the opinion of the Principal Investigator may compromise the subject's safety or the quality of the study data

Exclusion Criteria for Subjects with COPD

• History of acute exacerbation of COPD within 30 days of screening
• History of serious epistaxis within 14 days of screening
• Requirement of > 5 LPM nasal O2 to maintain an SpO2 > 90% while at rest
• History of pneumothorax secondary to lung bullae
• History of intolerance to supplemental oxygen
• Musculoskeletal or other non-pulmonary impairment that limits exercise tolerance
• Inability to achieve an optimal CWR level (4-7 minutes) during Study Visit 1R
• Current participation in another interventional study or participation within 14 days of screening
• Presence of any condition or abnormality that in the opinion of the Principal Investigator may compromise the subject's safety or the quality of the study data