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.

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