Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive Pulmonary Disease Patients
Conditions: Chronic Obstructive Pulmonary Disease, Noninvasive Ventilation
Sponsor: Philips Respironics

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 1 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
 
 
Clinical Protocol 
 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in 
Chronic Obstructive Pulmonary Disease Patients 
 
 
Protocol #: SRC-HRC-VectorEFLScreening-2018-10242 
 
Protocol Version: 4.0, April 12, 2022 
 
 
Written By: 
 
Chuck Cain 
 
 
 
 
 
           Date  
Director, Clinical Affairs 
 
Approved By: 
 
Kelli Davis 
 
 
 
 
 
 
Date  
Associate Director, Clinical Operations 
 
Approved By: 
 
Jeff Jasko 
 
 
 
 
 
 
Date  
Senior Data Scientist, Q&R Reg. & Clin. Affairs. - Biostatistics/DM 
 
 
Sponsored by 
 
 
Philips RS North America LLC f/k/a Respironics, Inc. 
 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 2 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Table of Contents 
 
Document Control Page(s) .................................................................................................................... 3 
Philips Contact Information .................................................................................................................. 4 
Protocol Revisions .................................................................................................................................. 6 
Glossary ..................................................................................................................................................... 7 
Protocol Synopsis ................................................................................................................................... 9 
I. 
Background Information .............................................................................................................. 10 
II. 
Study Objectives and Purpose ................................................................................................... 14 
III. 
Study Design: .............................................................................................................................. 15 
IV. 
Selection and Withdrawal of Subjects: ................................................................................ 17 
A. Inclusion Criteria .............................................................................................................. 17 
B. Exclusion Criteria: ............................................................................................................ 17 
C. Withdrawal: ...................................................................................................................... 18 
V. Treatment of Subjects: ...................................................................................................... 18 
A. Intended Use .................................................................................................................... 18 
B. Monitoring: ....................................................................................................................... 19 
VI. 
Assessment of Performance ......................................................................................... 19 
VII. 
Assessment of Safety .................................................................................................... 19 
VIII. 
Device Deficiencies ........................................................................................................ 20 
IX. 
Statistical Methods ........................................................................................................ 20 
X. Direct Access to Source Data / Documents .................................................................... 21 
XI. 
Quality Control and Quality Assurance ....................................................................... 22 
XII. 
Ethics .............................................................................................................................. 23 
XIII. 
Data Handling and Recordkeeping ............................................................................... 23 
XIV. 
Financing and Insurance ............................................................................................... 23 
XV. 
Registration on ClinicalTrials.gov or other applicable registry ................................. 23 
XVI. 
Risk and Benefit Analysis ............................................................................................. 23 
A. Potential Risks and Discomforts ...................................................................................... 23 
B. Potential Benefits ............................................................................................................. 24 
C. Compensation for Research-Related Activities ................................................................ 24 
References ................................................................................................................................. 24 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 4 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
 
Philips Contact Information 
 
Technical Assistance 
The following Philips employees are available for consultation, assistance, and/or 
problem solving during the course of this research study: 
Michael Kissel 
Sr. Staff, Systems Engineer 
 
 
 
Study Monitor(s): 
Melissa Weiner, MPH 
Senior Clinical Research Associate 
 
 
 
 
Kristi Seese, MBA 
Senior Clinical Research Associate 
 
 
 
Reporting of Adverse Events or Adverse Device Effects 
Report the occurrence of serious adverse event(s) or serious adverse device effect(s) to 
Philips within 24 hours of the occurrence. 
 
Melissa Weiner, MPH 
Senior Clinical Research Associate 
 
 
 
Kristi Seese, MBA 
Senior Clinical Research Associate 
 
 
 
 
 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 7 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
 
Glossary 
 
 
Apnea: the cessation of airflow at the nostrils and mouth for at least 10 seconds.  
Apnea/Hypopnea Index (AHI): the number of apneas and hypopneas per hour of 
sleep.   
AVAPS:  Automatically adjusts pressure to meet a target tidal volume. Inspiratory 
pressure fluctuates between the minimum and maximum settings to reach the set Tidal 
volume 
Bi-Level PAP Therapy: Two levels of pressure therapy, one during inspiration IPAP 
and another during expiration EPAP. 
COPD: Chronic Obstructive Pulmonary Disease 
CPAP Therapy: Continuous Positive Airway Pressure – delivers a constant pressure 
during inspiration and expiration. 
ODI: 4% Oxygen Desaturation Index 
EFL: Expiratory Flow Limitation - occurs when the airways become compressed which 
usually results when a pressure outside the airway exceeds the pressure inside the 
airway 
EPAP: Expiratory Positive Airway Pressure-Physician prescribed pressure for the 
expiratory (breathing out) phase of an individual on Bi-level PAP therapy  
FEV1: Forced Expiratory Volume in one second – the volume of air exhaled in the first 
second of the FVC maneuver and is the most reproducible measurement of airway 
obstruction. 
Final EPAP: EPAP that is determined to abolish EFL. 
FOT: Forced Oscillation Technique – A method to detect the presence of expiratory flow 
limitation. 
FVC: Forced Vital Capacity – Spirometry measurement in which the patient inhales 
maximally and then exhales as rapidly and completely as possible. 
IPAP: Inspiratory Positive Airway Pressure - Physician prescribed pressure for the 
inspiratory (breathing in) phase of an individual on Bi-level PAP therapy. 
Noninvasive Positive Pressure Ventilation (NPPV):  mechanical ventilation provided 
noninvasively (by mask or similar interface) rather than through an endotracheal tube or 
tracheostomy. 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 8 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Positive End Expiratory Pressure (PEEP): Pressure in the lungs (alveolar pressure) 
above atmospheric pressure (the pressure outside of the body) that exists at the end of 
expiration. 
OSA: Obstructive Sleep Apnea - a disorder in which complete or partial obstruction of 
the airway during sleep causes loud snoring, oxyhemoglobin desaturations and frequent 
arousals. 
S Mode: Spontaneous Ventilation – provides ventilation in synchrony with a person’s 
spontaneous breathing efforts; triggering of a breath cycle is only by the patient. 
S/T Mode: Spontaneous Timed Ventilation – provides ventilation in synchrony with a 
person’s spontaneous breathing efforts; triggering of a breath cycle is by the patient or 
the ventilator, should the person fail to trigger the ventilator after a preset time. In 
Spontaneous/Timed mode a "backup" rate is set to ensure that the patient still receives 
a minimum number of breaths per minute if they fail to breathe spontaneously. 
Zrs: total impedance of the respiratory system as measured by the forced oscillation 
technique (FOT) at a forcing frequency of 5 Hz. 
Xrs: the reactance (i.e. the imaginary component of the impedance) of the respiratory 
system as measured by the forced oscillation technique (FOT) at a forcing frequency of 
5 Hz. 
ΔXrs: Delta Xrs – is the difference between the mean value of Xrs during expiration 
(
exp
X
) and the mean value of Xrs during inspiration (
insp
X
). 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 9 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Protocol Synopsis 
 
Title: 
Determination of the Prevalence, and Severity of Expiratory 
Flow Limitation in Chronic Obstructive Pulmonary Disease 
Patients 
 
Study Design: 
Cross-sectional, non-randomized epidemiology study 
designed to assess the prevalence and severity of expiratory 
flow limitation in a community COPD population.  
 
Primary Objective: 
To gain insight and understanding on the prevalence and 
severity of expiratory flow limitation and how it relates to other 
physiological characteristics and endpoints in patients with 
COPD. For purposes of this trial, overall prevalence includes 
indeterminate EFL and EFL.  
Primary Endpoint: 
Overall Prevalence of EFL, as defined as the percentage of 
participants exhibiting a Delta Xrs value greater than or equal 
to 2.8. 
Other Objectives & 
Endpoints: 
See: II. Study Objectives and Purpose 
Study Population:    
Approximately 100 patients with COPD 
 
Study Type/Phase:     
Epidemiology Study 
 
Study Site: 
University of Florida Jacksonville 
Description of  
Study Intervention:        
Expiratory Flow Limitation detection via Non-Invasive 
Ventilation (NIV) device 
 
 
 
 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 10 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
I. Background Information 
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and 
mortality worldwide.   
Treatment options for COPD patients consist of medications, such as bronchodilators and 
anti-inflammatory drugs, pulmonary rehabilitation, long term oxygen therapy (LTOT), lung 
volume reduction surgery and lung transplantation.  Studies have shown that 
bronchodilators and anti-inflammatory drugs show minor or no benefit on long term 
outcomes but rather are used mainly for symptomatic relief.1  Pulmonary rehabilitation has 
been demonstrated to improve functional status and symptoms but there is lacking 
evidence on long term outcomes of this therapy. 2   Lung volume reduction surgery and 
lung transplantation is only appropriate for a small number of patients; therefore, there is 
no demonstration of improved long-term survival rate.3, 4 
Of these available therapies, few have been shown to significantly improve long term 
patient outcomes.  For the severe COPD patient, LTOT is the only treatment that 
demonstrated prolonged survival in controlled studies. 5, 6   But, despite the effectiveness of 
LTOT, COPD is still characterized by a high morbidity and mortality rate.   
Noninvasive positive pressure ventilation (NPPV) also known as noninvasive ventilation 
(NIV) is one therapy that may prove beneficial to stable COPD patients.  NIV is the use of 
positive pressure ventilation administered via a nasal or full face mask (that covers both 
the nose and mouth).  This type of ventilation has become a well-established and 
increasingly used therapeutic option for patients with hypercapnic respiratory failure (HRF) 
due to COPD.7  
NIV used nocturnally may improve nighttime hypoventilation that is common with COPD 
patients.  An improvement in nocturnal hypoventilation would reset the respiratory center 
sensitivity for CO2.8 9 This would result in an improvement in daytime gas exchange and 
sleep quality.  It is also known that hyperinflation in patients with COPD increases their 
work of breathing, thus fatiguing the respiratory muscles.10 It has been suggested that by 
applying nocturnal NIV it would allow the respiratory muscles to rest, resulting in muscle 
function recovery, increased respiratory muscle strength, reduced tendency for fatigue, 
and improvement in pulmonary function and gas exchange.11   
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 <70% 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 
the pressure outside the airway exceeds the pressure inside the airway.  As airflow 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 11 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
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 esophageal balloon or relatively 
complex plethysmographic techniques.  An alternative approach, and one that will be used 
in this study, involves the Forced Oscillation Technique (FOT).  
In 2003, Dellacà et al. proposed a new method to detect EFL during quiet breathing non-
invasively using the FOT. It was based on the observation that COPD patients with EFL 
developed large negative swings in the respiratory system input reactance measured at 
5Hz during expiration. They used this observation to define a sensitive and specific 
method of determining the presence of EFL. Normally the reactance reflects the elastic 
and inertial properties of the respiratory system but when flow limitation is present, the 
oscillatory signal cannot pass through the choke points and reach the alveoli. This 
produces a marked reduction in the apparent compliance and, consequently, a fall in Xrs.  
Although this Xrs reduction is present at all the frequencies, the greatest difference is seen 
at the lowest frequency. Since the quiet breathing signal can interfere with the estimation 
of Zrs at frequencies below 5 Hz, this frequency was used for the forcing signal. The 
difference between the mean value of Xrs during inspiration (
insp
X
) and 
exp
X
 , is 
called
rs
X

.  
Individuals with a ΔXrs value of:  
• less than 2.8 cm H2O/l/s are not flow limited 
• between 2.8 and 3.8 cm H2O/l/s, inclusive, have indeterminate EFL. Some 
breaths were calculated to be flow limited. 
• greater than 3.8 cm H2O/l/s have EFL. 
For purposes of this trial, participants who have indeterminate EFL or EFL (i.e., ΔXrs value 
is greater than or equal to 2.8 cm H2O/l/s) will continue to titration.  
This technology has been evaluated in numerous clinical studies for both the detection, 
reduction and abolishment of expiratory flow limitation in patients with COPD.  In 1956, 
Dubios et al., demonstrated the FOT method to be applicable to the measurement of 
airway resistance in patients, evaluation of therapeutic procedures designed to relieve 
airway obstruction, separation of airway resistance from tissue resistance, and study of the 
multiple factors that may affect airway resistance.1 And in additional work 2006, Dellaca et 
al., suggested the forced oscillation technique may be useful in chronic obstructive 
pulmonary disease patients using nasal pressure support by identifying continuous positive 
 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 12 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
airway pressure levels that support breathing without increasing lung volume, which in turn 
increase the work of breathing and reduce muscle effectiveness and efficiency.6 
The Vector project has incorporated this method as a new feature into the Philips BiPAP 
Ventilator (Murrysville, PA) overall platform (K121623).  The device has been designed to 
produce a 5 Hz sine wave with peak-to-peak amplitude of approximately 2 cmH2O 
superimposed upon the pressure and flow generated by the device. The resultant 
feedback waveform is then filtered and analyzed to measure reactance (delta Xrs) and 
thus determine if EFL is present. Subsequently, the EPAP (and concurrently and 
proportionally the IPAP) is increased until the EFL is essentially abolished (falls below the 
predetermined EFL threshold). Since this reactance is analyzed continuously (breath by 
breath) during both inspiration and expiration, it is relatively immune to external factors 
such as modest leaks or coughing / swallowing. 
Description of the Intervention Studied  
Study Device Descriptions: 
1. Vector Device 
The Vector ventilator is intended to provide non-invasive ventilatory support to treat adult 
patients with Respiratory Insufficiency with the primary cause being COPD.  It is intended 
to be used within the home, institution/hospital, and diagnostic laboratory environments. 
This device is not intended for life support. It can be used to screen for the presence, and 
abolishment, of Expiratory Flow Limitation.  
The Vector ventilation method auto-titrates PEEP or EPAP on a breath by breath basis.   
Vector is a new noninvasive method to continuously detect EFL during spontaneous 
breathing and minimizing it using EPAP. 
The device has been designed to produce a 5 Hz sine wave with peak to peak amplitude 
of approximately 2 cmH2O superimposed upon the pressure and flow generated by the 
device. The resultant feedback waveform is then filtered and analyzed to detect the 
change of a reactance (delta Xrs). Subsequently the EPAP (and concurrently and 
proportionally the IPAP) is increased until the EFL is essentially abolished (falls below the 
predetermined EFL threshold). Since this reactance is analyzed continuously (breath by 
breath) during both inspiration and expiration, it is relatively immune to external factors 
such as modest leaks or coughing / swallowing. Given that forced oscillation technique can 
be easily applied during noninvasive nasal ventilatory support, it could be used during 
routine noninvasive ventilation. 
This Vector screening mode is an automated five-minute screening test that can be done 
in a clinical environment under supervision to determine if EFL is present and its level of 
severity. 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 13 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
The screening test will have built-in logic that determines the test’s validity during the 
screening as well as the conclusion of the test.  The screening test will be at a relatively 
fixed pressure (typically between 3-4 cmH2O) that will remain constant throughout the 
session.  The screening session results, which will consist of near real-time pulmonary 
mechanic information, will be kept on a display until the next session is enabled. 
The Vector Ventilator is not currently approved by the FDA. It is considered an 
investigational device.  
 
2. Resmon Pro Device 
The Resmon Pro (St. Paul, MN) also uses the forced oscillation technique (FOT) 
which is a noninvasive method to measure the mechanical properties of the lung 
and airways during tidal breathing. In addition to measuring total impedance 
(resistance and reactance), the Resmon Pro can measure expiratory flow limitation 
which is a key index of respiratory obstruction. Restech has developed patented 
technology to determine the breath-by-breath presence and severity of expiratory 
flow limitation (EFL) during quiet breathing. Using the Resmon Pro, a physician can 
detect the presence, severity and reversibility of EFL, and evaluate the degree of 
airflow obstruction and shortness-of-breath experienced by the patient. 
The Resmon PRO FULL (K152585) is intended to measure respiratory system 
impedance using the Forced Oscillation Technique (FOT). Is intended for use with 
pediatric and adult patients 4 years of age or older. The device is designed to be 
used by pulmonologists, general practitioners, nurses, respiratory therapists, 
laboratory technologists, medical researchers and similarly trained personnel in 
hospitals, clinics, and private physician offices. 
Resmon PRO FULL consists of a main unit which has been designed to be used 
stand-alone, without the need of any personal computer, and an adjustable holder 
with a clamp to fix such unit to a table/desk and to regulate its height and orientation 
to the patient during an FOT test. 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 14 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
II. Study Objectives and Purpose  
Primary Objective 
To gain insight and understanding on the prevalence and severity of expiratory flow 
limitation and how it relates to other physiological characteristics and endpoints in patients 
with COPD. For purposes of this trial, overall prevalence includes indeterminate EFL and 
EFL.  
Secondary Objectives: To understand the correlation of the final EPAP with FEV1, final 
EPAP with screening delta Xrs value and the percent of participants with EFL per the 
Resmon Pro that have their EFL abolished during the Vector screening. 
 
Primary Endpoint: 
• Overall Prevalence of EFL, as defined as the percentage of participants exhibiting a 
Delta Xrs value greater than or equal to 2.8  
Secondary Endpoint: 
• Correlation of titrated Final EPAP to participants’ FEV1 
• Correlation of titrated Final EPAP to participants’ screening Delta Xrs value 
• Percent of participants with EFL per the Resmon Pro that have their EFL abolished 
during the Vector screening 
 
Exploratory Endpoints: – Correlation and relationship of participant’s therapy settings to 
the following: 
• Classification of COPD (Chronic Bronchitis or Emphysema) 
• Airflow limitation severity in COPD via Global Initiative for Chronic Obstructive Lung 
Disease (GOLD) classification 12  
• Presence of indeterminate EFL and EFL in a seated position 
• Presence of indeterminate EFL and EFL in a supine position 
• Quality of Life via COPD Assessment Test (CAT)13 score 
• Exacerbation History 
• Healthcare Utilization  
• Smoking History 
• Oxygen therapy usage 
• Documented PaCO2 
• Presence of Sleep Disordered Breathing and risk of obstructive sleep apnea (OSA) 
via STOP-BANG Questionnaire14 
• Therapy Comfort assessment via Questionnaires 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 15 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Device Related Exploratory Endpoints: 
• Vector Device collected parameters: Delta Xrs value, % flow limited breaths, Total 
System Resistance mask leak values 
• Comparison of Delta Rx calculation of the Resmon Pro at 5 Hz vs. Vector study 
ventilator 
• Correlation between screening Delta Xrs (measurement in liters per second) at final 
EPAP in cmH2O in supine position and any other variables from the analysis 
• Therapy Comfort assessment via Questionnaires 
 
Observational Endpoints/Learnings:  
• Clinicians will be able to know when EFL is present or not present through the 
screening feature of the Vector device 
• Understanding of how patients who present with varying degrees of EFL severity 
are being medically managed differently or similarly  
• Percentage of patients that were successfully screened as not having EFL by the 
Vector device but determined to have flow limitation measured by Resmon Pro  
 
III. Study Design: 
This will be a cross-sectional, non-randomized epidemiology study designed to assess the 
prevalence and severity of expiratory flow limitation in a community COPD population. In 
the study we will also investigate how the presence of EFL may correlate to other 
physiological biomarker endpoints in the COPD patient. 
 
Site COVID-19 safety procedures and documentation will be followed. Study devices and 
materials will either be single use or will be cleaned and disinfected per the Instructions for 
Use. 
 
Schedule of Events: 
Study Visit  
• Once the participant arrives, the study will be explained in full detail.  If the 
participant agrees, he/she will be consented into the study and the participant will 
be given a copy of the informed consent.  
• Once consent is obtained, and eligibility is confirmed the following study related 
procedures will be conducted: 
• Demographics:  gender, date of birth, ethnicity, race, level of education will be 
collected. 
• Current Medications: all current medications will be collected. 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 16 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
• Medical History Assessment: information will be collected regarding historical 
spirometry data, COPD history and other relevant medical history including the 
diagnosis of Sleep disordered breathing and Oxygen therapy usage. Chest 
computerized tomography (CT) scans will be collected if they have been done 
within the past two years. A new CT scan will not be required.  
• Physical examination with anthropometric data (weight, height, temperature) 
collected and vital signs to include heart rate (HR), blood pressure (BP), respiratory 
rate (RR), and oxygen saturation (SPO2) maintained at least 88% on room air, and 
chest auscultation. 
• Review of inclusion/exclusion to ensure participant is eligible to continue 
• Administration of Study Questionnaires 
• Mask Fitting:  Participants will have up to two mask fittings in order to determine the 
best possible masks while using the Vector NIV device during the EFL screening 
and titration 
• Spirometry testing will be performed for participants who have not had a test in the 
previous 6 months 
Resmon Pro EFL Measurement 
• Participants may be required to wear nose clips during the measurement 
• Participants will also be required to hold their cheeks during the measurement to 
prevent any air leaks around their mouth.  
• While seated, participants will be instructed to breathe normally into the device for 
at least 30 seconds or until at least 10 breaths were successfully accepted by the 
device 
• Participants will be asked to repeat test while in the supine or semi-recumbent 
position. 
Vector EFL Screening/Determination and EPAP Titration 
• EFL Determination: The participant will be asked to breathe quietly into the Vector 
device using the selected mask for 5 minutes in the seated position, and then an 
additional 5 minutes while in the supine or semi-recumbent position.  This device 
has the capability of detecting EFL.  If it is determined that the participant does not 
have EFL or indeterminate EFL by the device screening indicator, the participant 
will not continue with the EPAP titration. 
• EPAP Titration: if it is determined by the Vector NIV device that the participant has 
indeterminate EFL or EFL (ΔXrs value is greater than or equal to 2.8 cm H2O/l/s) 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 17 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
the Vector NIV device will be changed from screening mode to therapy mode to 
delivery BiPAP therapy with the following settings.   
Vector Device Settings: 
• Pressure Support 
 
            
6 cmH2O  
• Max Pressure 
 
 
 
26 cmH2O 
• EPAP Min / EPAP Max 
 
 
4 / 20 cmH2O  
 
• The participants will then breathe on the Vector NIV device in the supine position 
(preferred) or semi-recumbent if needed for approximately an additional 20 minutes. 
During the additional 20 minutes of breathing, the device will automatically increase 
the EPAP (and concurrently and proportionally the IPAP) until the EFL is abolished 
(or falls below the predetermined EFL threshold).  
• While the automatic EPAP Titration is being performed, all participants’ SpO2 will be 
monitored via finger pulse oximetry.  
• Patient must stay awake during the EPAP Titration. If the patient falls asleep, they 
will be woken by study staff. 
• The Final EPAP that is determined to abolish the participants’ EFL will be recorded. 
This value may be assessed by a Philips staff member using a software program 
designed to determine this value.  
• Participants will complete an EFL Vector device post questionnaire 
Unscheduled Visits: 
This is a single visit study. There are no anticipated unscheduled visits.  
IV. Selection and Withdrawal of Subjects: 
A. Inclusion Criteria 
1. Age > 40 years of age; < 80 years of age 
2. Ability to provide consent 
3. Diagnosis of COPD 
B. Exclusion Criteria:  
1. Any major non COPD uncontrolled disease or condition, such as congestive heart 
failure, malignancy, 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 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 18 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
2. Suffering from a COPD exacerbation at the time of data collection or in the 30 
days prior to data collection 
3. Self-reported Pregnancy 
4. Employee or family member that is affiliated with Philips Respironics 
5. History of bullous emphysema 
6. History of pneumothorax 
7. Evidence of acute sinusitis or otitis media 
8. Hypotension 
9. Participants at risk for aspiration of gastric contents 
10.    Epistaxis 
11.    Participants in respiratory failure 
12.    Inability to maintain a patent airway or adequately clear secretions  
C. Withdrawal: 
The term “discontinuation” refers to the participant’s premature withdrawal from the study 
prior to completing all procedures.  Participants may be discontinued from the study for 
any of the following reasons: 
• If in the investigator’s judgement, continuation in the study may prove harmful to the 
participant.  Such a decision may be precipitated by adverse events, including fever, 
nausea, rash, changes in vital signs, or the development of a new medical 
condition.  The investigator will be solely responsible for making medical/safety 
decisions regarding the participant’s continued participation in the study. 
• Noncompliance;  
• At the request of the participant. 
The study team will document whether or not each participant completed the study.  If, for 
any participant, study treatment or assessments were discontinued, the reason will be 
recorded. 
The study goal is to have 100 participants successfully complete the study.   
V. Treatment of Subjects: 
A. Intended Use  
Vector Device Intended Use 
The Vector ventilator is intended to provide non-invasive ventilatory support to treat adult 
patients with Obstructive Sleep Apnea (OSA), or Respiratory Insufficiency with primary 
cause being Chronic Obstructive Pulmonary Disease (COPD).  This device is not intended 
for life support. It may be used to screen for the presence, and abolishment of Expiratory 
Flow Limitation. It is intended to be used within the home, institution/hospital, and 
diagnostic laboratory environments.  

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 19 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Contraindications: 
• Existing respiratory failure  
• Acute sinusitis, otitis media 
• Hypotension 
• At risk for aspiration of gastric contents 
• Epistaxis, causing pulmonary aspiration of blood 
• Inability to maintain a patent airway or adequately clear secretions  
 
 
Resmon Pro Intended Use 
The Resmon PRO FULL is intended for the measurement and collection of lung 
function parameters in humans. The system performs cooperation-independent 
measurements of respiratory system impedance using the Forced Oscillation 
Technique (FOT). The device is useful in the field of early diagnosis, in every-day-
routine testing, for clinical trend observations as well as for epidemiologic studies. FOT 
is suitable for adult, geriatric and pediatric studies. The device is designed to be used 
by pulmonologists, general practitioners, nurses, respiratory therapists, laboratory 
technologists, medical researchers and similarly trained personnel in hospitals, clinics 
and private physician offices 
B. Monitoring: 
This clinical study will be monitored by Philips (Sponsor) in compliance with the Code of 
Federal Regulations (CFR) for clinical research; namely, 21 CFR Parts 50, 54, 56 and 812 
and others as applicable. The purpose of such monitoring is to assure that the study 
remains in compliance with the approved protocol, investigator agreement and regulatory 
requirements, to verify the completeness, reliability and accuracy of study data and to 
resolve any issues that arise during the conduction of the study. The Sponsor will conduct 
monitoring visits periodically as specified by the monitoring plan. Monitoring will be conduct 
by trained clinical research professionals.  
It has been determined that this study does not require a Data Safety Monitoring Board 
(DSMB). 
VI. Assessment of Performance  
Device performance will be based on the following recorded Ventilator parameters: 
• Ventilator collected parameters during the EFL screening and titration; delta Xrs 
value, % flow limited breaths, EPAP values and mask leak values. 
 
VII. Assessment of Safety  
All serious adverse events occurring during the course of the study and up to 72 hours 
post study visit will be collected, fully documented, and reported to Western Institutional 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 20 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Review Board by the Principal Investigator, Dr. Mariam Louis, MD or sponsor staff per IRB 
guidelines. Serious adverse events will be reviewed by the Sponsor within 24 hours of the 
study team being aware of the event.  
A serious adverse event (SAE) is an adverse event: 
• Resulting in death, or 
• Resulting in a serious deterioration in the health of the subject that: 
o Results in a life-threatening illness or injury, 
o Results in a permanent impairment of a body structure or body function, 
o Requires inpatient hospitalization or prolongation of existing 
hospitalization, or 
o Results in medical or surgical intervention to prevent permanent 
impairment of a body structure or body function. 
 
All unexpected adverse events during the course of the study and up to 72 hours post 
study visit will be collected and reviewed.  As any events will be reported electronically or 
directly from a person, the study team will collect the onset, duration, intensity and 
treatment required, outcome and action taken. In addition to adverse event reporting, the 
study staff will report a summary of the protocol findings, participant recruitment, drop-outs, 
and events to the IRB annually.  
VIII. Device Deficiencies  
All device deficiencies, use or user errors, and equipment failures will be documented.  
Use or User errors will be captured as part of the source documentation.  Device 
deficiencies and equipment failures will be kept on a separate log.  The serial numbers and 
type of deficiency/failure will be captured. Unanticipated device deficiencies that lead to 
SAE’s will be reviewed with the PI and reported to the IRB as required.  
IX. Statistical Methods  
Determination of Sample Size 
Approximately 100 participants will be enrolled.  No power analysis was performed.  
 
General Considerations 
Descriptive statistics will be presented for all variables of interest.   Continuous data will be 
summarized by mean, standard deviation, median, minimum, and maximum values.  
Categorical data will be presented as frequencies and percentages. Any formal 
significance testing will be performed at p < 0.05. 
 
There are no statistical criteria for terminating the study, and any deviations to the original 
statistical plan will be noted in the analysis report. 
 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 21 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Primary Analysis 
The primary analysis will calculate the prevalence of EFL, including the 95% Binomial 
confidence interval (CI).  
 
Secondary Analysis 
Correlations between device parameters and efficacy outcomes will be performed using 
Pearson and Spearman correlation.  Percentage of participants exhibiting EFL 
abolishment with Vector therapy will be presented, including the 95% Binomial confidence 
interval (CI). 
 
Exploratory Analysis 
Various exploratory analyses may be performed to help evaluate participant’s therapy 
settings with other baseline data or outcomes, but these analyses are not required for the 
final report 
 
Participant Disposition 
Participant disposition, including the total number of participants enrolled, completed, early 
terminations and withdrawals, will be presented. A listing will be provided with the reasons 
for discontinuation. 
 
Safety Analysis 
Safety evaluations will be performed by recording clinical adverse events at the time 
originally reported, and they will be followed at regular intervals until resolution or study 
completion, whichever comes first.  Adverse events will be provided in data listings. 
 
Interim Analysis 
An interim analysis may be performed after approximately 50% of the planned study 
population has completed the study.  
X. Direct Access to Source Data / Documents  
Only site clinical study staff will know the identity of the participants.  All information 
recorded by the study team and provided for analysis will be given a study ID number.  
Privacy rules and requirements according to federal and state governing regulations will be 
implemented. All the information collected as part of this study will be kept confidential. All 
information collected for this study will be kept in a secured area or stored in a password 
protected computer if digital. Except when required by law, participants will not be 
identified by name, social security number, address, telephone number, or any other direct 
personal identifier in study records. For records disclosed to Philips participants will be 
assigned a unique code number.   

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 22 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
Results of the study related data, medical history, and information obtained from the 
questionnaire and device data will be reported and received by Philips.  Philips will use 
participant study data for research purposes to support objectives described in this 
protocol.   
In addition, participant records may be reviewed in order to meet federal and state 
regulations.  Reviewers may include representatives from the FDA or similar government 
authorities in other countries where the device is being used, and Philips for the purposes 
of the following side effects, and to gather additional information related to the study, and 
the Institutional Review Board (IRB).  Participant permission for review of confidential 
information is granted by signing the associated informed consent.  Philips will ensure that 
it follows all applicable state and federal data protection regulations.  
A. Provisions to Protect the Privacy Interests of Participants:   
Participants will only interact with approved members of the research staff and will have 
the option to decline to provide any information that they are uncomfortable revealing. All 
research staff (site and sponsor) will receive training regarding the protection of human 
subject data.  Participant’s medical records will only be accessed after obtaining written 
consent from the participant, and will only be reviewed by members of the research staff 
for whom review of this information is necessary for continued participation in the study 
(e.g. Philips research staff and study investigator reviewing the medical records). 
 
B. Case Report Forms  
The site study team will capture information on source documents. Data from source 
documents will be entered into an electronic data capture system (EDC) and will be 
monitored according to monitoring plan by the study sponsor.  Copies of the source will 
remain with the site.  Only staff delegated by the PI will have the ability to enter in, or make 
changes to, the source documents.  All data collected and maintained by the sponsor, will 
be kept confidential, and stored in a secure location if on paper or on a secure server or 
protected device.  
XI. Quality Control and Quality Assurance  
The PI and study personnel will be trained to the study protocol, study product, TMF 
documents, monitoring plan, CRFs and/or eCRFs, direct data reporting, and all Sponsor 
expectations, as applicable. Once complete, training and delegations will be documented 
for PI and study personnel. 
Data queries will be addressed by delegated study personnel and CRF/ eCRFs will be 
reviewed and signed off by PI prior to study closure. Monitoring will be completed in 
accordance with US CFR, ICH-E6 GCP Section 6, and ISO 14155:2011 as applicable.     

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 23 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
XII. Ethics  
This study will be submitted and reviewed by the Western Institutional Review Board.  All 
participants will be consented prior to completing the trial. The Principal Investigator will 
review all adverse events as it relates to the study device. 
All data will be kept confidential and in a secure location if on paper or on a secure server 
or device. Only approved study personnel will have access to study related documents. All 
electronic data shall be stored in a coded data set.  All paper documents shall be kept in a 
secure area.  Study data and source will be made available for study related monitoring or 
audits by the IRB/IEC, sponsor, or regulatory inspection(s).   Results of the study related 
data, and information obtained from the engineering study, will be collected, received and 
reported by Philips.  Philips will use participant study data for research purposes to support 
scientific and marketing objectives described in this protocol.   
XIII. Data Handling and Recordkeeping  
Hard copies of the study will be kept on site for at least 2 years after study completion.  
The sponsor will maintain study records indefinitely. Records will be stored at Iron 
Mountain, a secure information management services company.  
XIV. Financing and Insurance  
If the participant is injured during the course of the trial and as a direct result of this trial, 
they should contact the Principal Investigator, Mariam Louis, MD. The participant will be 
directed to seek clinically appropriate medical care for that injury. However, we cannot 
guarantee that the medical care and treatment will be provided without charge or that it will 
be paid for by the participants insurance company, and the costs incurred may ultimately 
be the participant’s responsibility.  
 
XV. Registration on ClinicalTrials.gov or other applicable 
registry  
This trial will be registered on Clinical Trials.gov. It is the intent that these data may be 
used for to support regulatory clearance and/or consideration for a submission to peer 
review publication. 
XVI. Risk and Benefit Analysis  
A. Potential Risks and Discomforts 
This is a minimal risk study. Potential risks are detailed below and will be listed in the ICF 
and discussed during the consenting process. 
 
We believe that the risks of providing noninvasive ventilation with the Vector NIV device 
are no greater than the risks encountered with other assisted positive airway pressure 
(PAP) devices. We believe that no significant risks will be posed to the participants 
participating in this protocol, as the study is noninvasive and will be conducted in a clinical 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 24 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
supervised setting by trained clinical staff. The equipment has been tested to ensure 
safety. Should the equipment not perform as designed, therapy could increase and / or 
decrease more than desired. This affect could be uncomfortable. 
A trained study staff member will be present monitoring the participant while the device is 
in use at the clinic. The study staff member will intervene should any problems be 
identified. One possible intervention could be for the staff to stop the study in the event that 
participant’s oxygen saturation (SpO2) falls below 88%. The participant can also easily 
remove their interface device should it become uncomfortable or make breathing difficult. 
Other potential side effects of PAP therapy may include: ear discomfort, conjunctivitis, skin 
abrasions due to non-invasive interfaces and gastric distension (aerophagia), all of which 
are quite uncommon. Thus, we believe that the risks and discomfort are minimal. 
COVID-19 is a risk with any in-person activity, but proper mitigation strategies, including 
COVID-19 screening, disinfection, and other site safety procedures, will be implemented to 
minimize patient risk. 
We believe that the risks and discomforts associated with this study are minimal.  
B. Potential Benefits 
Although participation in this trial will not result in any direct benefit to the subjects, they 
will be contributing to generalizable data that will help provide the sponsor and investigator 
more insight into the prevalence of expiratory flow limitation in the COPD patient 
population. 
C. Compensation for Research-Related Activities 
Participants will only be compensated $75 for participation in the study. Payment for 
participation will be handled through the University of Florida’s Human Subject Payment 
(HSP) Program. 
References  
1. Rennard SI, Serby CW, Ghafouri M, et al. Extended therapy with ipratropium is 
associated with improved lung function in patients with COPD. Chest 1996; 110: 62-70 
2. Reis AL, Kaplan RM, Limberg TM, et al. Effects of pulmonary rehabilitation on 
physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary 
disease. Ann Intern Med 1995; 122: 823-832 
3. Lung transplantation: report of the ATS workshop on lung transplantation: American 
Thoracic Society, Medical Section of the American Lung Association. Am Rev Respir Dis 
1993; 147: 772-776 
4. Benditt JO, Albert RK. Lung reduction surgery: great expectation and a cautionary note. 
Chest 1995; 107: 297-298 

 
Determination of the Prevalence and Severity of Expiratory Flow Limitation in Chronic Obstructive 
Pulmonary Disease Patients 
 
Version 4.0, 12APR2022 
Page 25 of 25 
Confidential 
Protocol # SRC-HRC-VectorEFLScreening-2018-10242  
5. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: 
a clinical trial: Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93: 391-398 
6. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating 
chronic bronchitis and emphysema: report of the Medical Research Council working party. 
Lancet 1981; 1: 681-686 
7. Windisch W., et al, Outcome of Patients with Stable COPD Receiving Controlled 
Noninvasive Positive Pressure Ventilation Aimed at a Maximal Reduction of PaCO2. Chest 
2005; 128: 657-662  
8. Douglas NJ, Calverley PMA, Legget RJE, et al. Transient hypoxaemia during sleep in 
chronic bronchitis and emphysema. Lancet 1979; 1: 1-4 
9. Roussos C. Function and fatigue of respiratory muscles. Chest 1985; 88: 124S-132S 
10. Hill N, Leger P, Criner G. Clinical indications for noninvasive positive pressure 
ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and 
nocturnal hypoventilation – a consensus conference report. Chest 1999; 116: 521-534 
11. Braun NM, Marino WD. Effect of daily intermittent rest of respiratory muscles in 
patients with severe chronic airflow limitation (CAL). Chest 1984; 85: 59S-60S 
12. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, 
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018. ; 2018 
(https://goldcopd.org/) 
13. Jones PW, Harding G, Berry P, Wiklund I, Chen W-H, Kline Leidy N. Development and 
first validation of the COPD Assessment Test. Eur Respir J 2009; 34: 648–654.   
14. Chung F, Yegneswaran B,  Liao P, et al. STOP questionnaire: a tool to screen patients 
for obstructive sleep apnea, Anesthesiology 2008; 108: 812-21.