The Use of High Frequency Oscillations With NIV in Hypercapnic COPD Participants
The Use of High Frequency Oscillations With NIV in Hypercapnic COPD Participants
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and
 mortality throughout the world, being the fourth leading cause of death in the world.

 This study is designed to detect COPD participants with Expiratory Flow Limitation. EFL
 occurs when the airways become compressed which usually results when a pressure outside the
 airway exceeds the pressure inside the airway.

 Participants will undergo study eligibility procedures at visit 1. At visit 2 participants
 will undergo a baseline auto-EPAP (Expiratory Positive Airway Pressure) measurement. Then the
 order will be randomized to three different treatment methods. Between each treatment there
 will be at least a 10 minute washout period in order for CO2 to stabilize and return to
 baseline.
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and
 mortality throughout the world, being the fourth leading cause of death in the world.

 COPD is a disease that results in varying degrees of dyspnea, or shortness of breath.
 Spirometry is a method of diagnosing COPD with the presence of a post bronchodilator FEV1
 <80% of the predicted value in combination with an FEV1 / FVC <70%. This would confirm that
 there is a presence of airflow limitation that is not fully reversible.

 The presence of airflow limitation has been identified as one of the main causes of dyspnea
 in patients with chronic obstructive pulmonary disease (1). Expiratory Flow Limitation (EFL)
 occurs when the airways become compressed which usually results when a pressure outside the
 airway exceeds the pressure inside the airway. As an airflow obstruction worsens, EFL appears
 at much lower flows for a given lung volume and it becomes present at rest or at least
 develops early during exercise (2).

 Early detection of EFL consisted of either invasive balloon catheterization or relatively
 complex plethysmographic techniques. An alternative approach, and one that will be used in
 this study, involves utilizing the Forced Oscillation Technique (FOT).

 Alternatively High Frequency Oscillations (HFO) has shown to effectively lower CO2 levels,
 but traditionally require intubation or a trans tracheal catheter. Treatment with a
 specialized noninvasive ventilator is possible and it is proposed that therapy can be
 augmented by the application of an optimized EPAP to splint open the lower airways in order
 to increase the diffusive capabilities of the high frequency oscillations into lower alveolar
 regions. There are approximately 25 million hypercapnic patients with EFL that could benefit
 from this therapy. High frequency oscillations integrated into a specialized noninvasive
 ventilator has the advantages of lower cost than other solutions and significantly lower
 medical risks. In addition, high frequency oscillation uses lower pressures to achieve
 effective therapy which means less chance of barotrauma and greater patient acceptance.

 This study will enroll subjects at a screening visit. Screening will include a physical exam
 and vital signs, pregnancy test (if applicable), questionnaires, pulse oximetry, measure of
 carbon dioxide levels, determination of EFL by an auto- Expiratory Positive Airway Pressure
 (EPAP) ventilator, and spirometry.

 If the patient is eligible and tolerates the above procedures, they will be asked to complete
 an in home-based sleep study prior to visit 2. Alice Night One/ Alice PDX are portable home
 sleep testing devices that record information about breathing.

 At visit 2 participants will be monitored continuously via a 3 lead EKG, oxygen saturation by
 pulse oximetry (SPO2), Carbon Dioxide concentration(TcCO2) monitor, RespiTrace belt and
 ventilator data.

 During Visit 2, participants will first undergo a repeat optimal EPAP determination and then
 trial 3 different sessions of High Frequency Oscillation (HFO) therapy for 20 minutes with at
 least a 10 minute wash out period between each session to allow the participant's CO2 to
 stabilize or return to baseline. The order of the sessions will be randomized for each
 patient. Participants will be placed in a semi-recumbent position and wear a nasal CPAP mask
 for each session. A TcCO2 monitor patch will be placed on the skin (forehead area) to collect
 carbon dioxide measurements during each session. A RespiTrace belt will placed on the
 participants' chest wall to measure chest wall and diaphragmatic excursion during each
 session. A 3 lead EKG will also be used to monitor cardiac activity during each session.
Inclusion Criteria:

 -  Age > 21 years of age; < 85 years of age

 -  Participants that have been physician diagnosed (primary diagnosis) with Obstructive
 Airway Disease (to include:Chronic Obstructive Pulmonary Disease (COPD);
 Bronchiectasis; Severe Asthma); forced expiratory volume in 1 second (FEV1) < 60%
 FEV1/ forced vital capacity (FVC) <60%

 -  Arterial CO2 > 45 mmHg as determined by blood gas (PaCO2) or transcutaneous (tcCO2)
 >50 within the past month

 -  Ability to provide consent

 -  Participant has not used Non-Invasive Ventilation (BiPAP/CPAP) therapy in the past 8
 hours

 -  Participant has no child bearing potential OR a negative pregnancy test in a woman of
 childbearing potential

 Exclusion Criteria:

 -  Participants that have not returned to their baseline health status from an
 exacerbation of COPD or other pulmonary problems or have not established at least two
 weeks of stability at a new baseline.

 -  Use of antibiotics or prednisone for a COPD exacerbation within the previous 4 weeks.

 -  Uncontrolled Hypertension

 -  Participants that require greater than 3 liters of oxygen at rest

 -  History of cardiovascular instability, including uncontrolled ventricular arrhythmias,
 angina, diastolic BP > 100 mmHg and all Participants with pacemakers

 -  Any major non-COPD uncontrolled disease or condition, such as congestive heart
 failure, malignancy, end-stage heart disease, liver or renal insufficiency (that
 requires current evaluation for liver or renal transplantation or dialysis),
 amyotrophic lateral sclerosis, or severe stroke, or other condition as deemed
 appropriate by investigator as determined by review of medical history and / or
 participant reported medical history

 -  History of pneumothorax

 -  Apnea Hypopnea Index (AHI) > 15 via in-home sleep study

 -  Excessive alcohol intake (> 6oz hard liquor, 48 oz. beer or 20 oz. wine daily), or
 illicit drug use by review of medical history and / or participant reported medical
 history

 -  Daily use of prescribed narcotics (greater than 30 mg morphine equivalent)

 -  History of Giant bullous emphysema

 -  A positive urine pregnancy test when screening for study