A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) Therapy on Re-hospitalization in Patients With Sleep-Disordered Breathing With Co-morbid COPD
Phase: NA
Conditions: Breathing-Related Sleep Disorder
Sponsor: Philips Respironics

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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HRC-1426-BBACK-MS 
 
Protocol Title: 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to 
Assess the Effects of a Novel Application of Averaged Volume Assured 
Pressure Support Ventilation (AVAPS-AE) therapy on Re-hospitalization in 
Patients with Sleep-Disordered Breathing with co-morbid COPD. (STOP-
BOUNCEBACK study) 
 
 
Protocol Number: 
 
HRC-1426-BBACK-MS 
 
 
Revision: 
 
 
Rev. 5.0; March 8, 2017 
 
Principal Investigator:         Dr. Sairam Parthasarathy 
University of Arizona 
1501 North Campbell Ave., Ste. 2349 
Tucson, AZ 85724 
 
 
 
 
Sponsor: 
 
 
Respironics, Inc., doing business as Philips Healthcare  
(“Philips Respironics”) 
 
 
 
 
1740 Golden Mile Highway 
 
 
 
 
Monroeville, PA 15146 
1-(724)-387-7500 
http://www.respironics.com/ 
 
 
Confidential 
 
This protocol, its contents and the information relating to it are the proprietary property of Philips 
Respironics, Inc. All information is to be kept confidential. 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Investigator Agreement 
 
As Investigator of the study titled “A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study 
to Assess the Effects of a Novel Application of Averaged Volume Assured Pressure Support Ventilation 
(AVAPS-AE) therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid 
COPD.  (the “Study”), I agree to:  
 
(i) conduct the Study in accordance with: this Investigator Agreement; the Study’s Protocol as approved by 
the Institutional Review Board (IRB) (the “Protocol”); all applicable laws and regulations; and any IRB or 
FDA conditions of approval;   
(ii) await IRB approval for the Protocol before obtaining informed consents; 
(iii) ensure that all requirements for informed consent are met and not let any subject participate in the Study 
before obtaining that subject’s informed consent;  
(iv) not make modifications to the Protocol as supplied to me by Philips Respironics, Inc. (the “Sponsor”), 
without first obtaining the written approval of the Sponsor;  
(v) provide the Sponsor with accurate financial information as required by FDA regulations; 
(vi) supervise all testing of investigational devices that involves any Study subject;  
(vii) maintain Study documentation for the period of time as required by FDA regulations; and 
(viii) supply to the Sponsor, as part of this Investigator Agreement, my curriculum vitae. 
 
 
INVESTIGATOR 
 
 
 
 
 
 
Signature:____________________________________________________________ 
 
Printed Name: ________________________________________________________ 
 
 
 
Date:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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GLOSSARY OF DEFINITIONS AND TERMS ....................................................................................... 4 
DOCUMENT CONTROL PAGE ............................................................................................................... 6 
PROTOCOL REVISIONS .......................................................................................................................... 7 
II. STUDY DESIGN ..................................................................................................................................... 9 
III. STUDY OBJECTIVES/ENDPOINTS ............................................................................................... 10 
IV. SUBJECT SELECTION ..................................................................................................................... 11 
V. STUDY ENROLLMENT ..................................................................................................................... 12 
VI. STUDY PROCEDURES ..................................................................................................................... 12 
VII. RISKS AND DISCOMFORTS ......................................................................................................... 19 
VIII. POTENTIAL BENEFITS ................................................................................................................ 21 
IX. MONITORING AND QUALITY ASSURANCE ............................................................................. 21 
X. REFERENCES ...................................................................................................................................... 22 
 
 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Glossary of Definitions and Terms 
 
Apnea: The cessation of airflow at the nostrils and mouth for at least 10 seconds as determined using 
nasal-oral thermistor or device flow. 
 
Apnea/Hypopnea Index (AHI): The number of apneas and hypopneas per hour of sleep.   
 
AVAPS-AE: A mode of therapy that automatically adjusts EPAP in response to patient events such as 
snores, leak, and apneas/hypopneas, provides an automatic back up rate, and automatically adjusts 
pressure support in order to maintain the target tidal volume. 
 
Average Volume Assured Pressure Support (AVAPS): Positive airway pressure support that provides 
a gradual pressure change based on the average of the preceding several breaths to maintain the target 
tidal volume. 
 
Bilevel PAP Therapy: Responds to both inspiration and expiration by the patient and delivers a set 
amount of pressure when the patient begins spontaneous inhalation and decreasing pressure when 
exhalation begins. 
 
CPAP Therapy: Continuous Positive Airway Pressure – delivers a constant pressure during inspiration 
and expiration. 
 
COPD: Chronic Obstructive Pulmonary Disease 
 
Compliance: adhering to or conforming to a regimen of treatment such as CPAP or Bi-PAP.  
 
EPAP: Expiratory Positive Airway Pressure-Physician prescribed pressure for the expiratory (breathing 
out) phase of an individual on Bi-level PAP therapy  
 
 
Hypopnea: Shallow breathing in which the air flow in and out of the airway is significantly reduced as 
detected by nasal pressure or device flow - often associated with oxygen desaturation of 4% or EEG 
arousal. 
 
IPAP: Inspiratory Positive Airway Pressure - Physician prescribed pressure for the inspiratory (breathing 
in) phase of an individual on Bi-level PAP therapy. 
 
Mode of Ventilation:  Represents a combination of control, phase and conditional variables that establish 
a set pattern of spontaneous and/or mandatory breaths. 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Noninvasive Positive Pressure Ventilation (NPPV):  Mechanical ventilation provided noninvasively 
(by mask or similar interface) rather than through an endotracheal tube or tracheostomy. 
 
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. 
 
Polysomnography:  Continuous and simultaneous recording of physiological variables during sleep, i.e., 
EEG, EOG, EMG (the three basic stage scoring parameters), EKG, respiratory air flow, respiratory 
excursion, lower limb movement, and other electrophysiological variables. 
 
Spirometry: Measurement by means of a spirometer of the air entering and leaving the lungs. 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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DOCUMENT CONTROL PAGE 
 
Study Name 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a Novel 
Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) therapy on Re-
hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. (STOP-
BOUNCEBACK study) 
 
Protocol Number 
HRC-1426-BBACK-MS 
 
Protocol Version 
5.0 
 
Version Date 
March 8, 2017 
 
Sponsor 
Philips Respironics, Inc. 
1740 Golden Mile Highway 
Monroeville, PA 15146 
Phone: 1-800-387-7500 
http://www.respironics.com 
 
 
Study Monitor(s) 
Chuck Cain, BS 
 
 
 
 
Tiffani Bowers, LPN 
Manager, Clinical Research  
 
 
Clinical Research Associate 
Philips Healthcare 
 
 
 
 
Philips Healthcare 
1010 Murry Ridge Lane 
 
 
 
1010 Murry Ridge Lane 
Murrysville, PA 15668 
 
 
 
Murrysville, PA 15668                                                                   
Tel:  724-733-5835 
 
 
 
 
Tel: 724-387-4569 
Mobile: 412-657-1874 
 
 
 
Mobile: 724-989-3072 
E-mail:  chuck.cain@philips.com 
 
 
E-mail: tiffani.bowers@philips.com 
 
 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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PROTOCOL REVISIONS 
 
Rev 
Level 
 
Changes Made for HRC-1426-BBACK-
MS 
 
Date 
 
Contributors 
0.0 
Initial Draft 
01/08/2015 
S. Parthasarathy, C. Cain, 
G. Lotz 
1.0 
Revisions  
03/23/2015 
C. Cain, L, Ostrowski, S. 
Parthasarathy 
2.0 
Revisions 
1/15/2016 
C. Cain L. Ostrowski, S. 
Parthasarathy 
3.0 
Updated Study Monitor Information. 
Updated Pap Wash-In Criteria. Removed 
“Acute Respiratory Failure” from 
Exclusionary Criteria; Removed “Alice 
PDX” verbiage. Add additional site 
Banner-University Medical Center South 
2800 E. Ajo Way Tucson, AZ 85713 
11/22/2016 
T. Bowers 
4.0 
1.) Update Inclusion Criteria by 
removing “ prior non-elective 
hospitalization (one in past 12 
months) OR active smoker”  
 
01/17/2017 
S. Parthasarathy, C. Cain, 
A. Valentin 
5.0 
Updated Inclusionary content to state “a 
primary or secondary admission diagnosis 
of COPD”, Removed Inclusionary Criteria 
section 2 part (b). Updates to the final table 
03/08/2017 
S. Parthasarathy, T. 
Bowers, C. Morton, C. 
Cain, G. Lotz 
 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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I. Background  
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in America, claiming the 
lives of 133,965 Americans in 2009  (1). In 2011, 12.7 million U.S. adults (aged 18 and over) were estimated 
to have COPD(2). However, close to 24 million U.S. adults have evidence of impaired lung function, 
indicating an under diagnosis of COPD (3). An estimated 715,000 hospital discharges were reported in 2010; 
a discharge rate of 23.2 per 100,000 population (3). COPD is an important cause of hospitalization in our 
aged population. Approximately 65% of discharges were in the 65 years and older population in 2010. In 
2010, the cost to the nation for COPD was projected to be approximately $49.9 billion, including $29.5 
billion in direct health care expenditures, $8.0 billion in indirect morbidity costs and $12.4 billion in indirect 
mortality costs (3). Innovative improvements in care delivery, including novel device-based therapies, could 
potentially reduce re-hospitalizations, healthcare costs, and public health burden due to COPD.  
 
Across a selection of 15 states in 2008, there were 190,700 index admissions with a principal diagnosis of 
COPD among patients 40 years old and older (4). The 30-day readmission rate for a principal diagnosis of 
COPD was 7.1 percent and the rate of 30-day readmissions for any diagnosis of COPD was 17.3 percent (4, 
5). If all readmissions were counted regardless of diagnosis, one out of five index admissions for COPD 
(20.5 percent) were followed by a readmission within 30 days (4, 5). Healthcare costs were consistently higher 
for readmissions than for initial stays (5). On average, costs for a 30-day readmission with COPD as principal 
diagnosis were 18 percent higher than for the index stay. Costs were more than 50 percent higher for the 
readmission with COPD as any diagnosis or for all-cause readmissions.  Healthcare costs due to COPD 
could be greatly reduced by innovative interventions aimed at reducing risk for readmission.  
 
Currently, Medicare patients who are readmitted within 30-days could result in significant fines to 
healthcare providers and institutions. Innovations in healthcare delivery aided by device technology that 
expeditiously facilitates positive airway pressure therapy could mitigate such financial liabilities. Averaged 
Volume Assured Pressure Support –Auto EPAP (AVAPS-AE) device can not only prevent the nocturnal 
hypoventilation due to COPD, but also treat coexisted obstructive sleep apnea (6). AVAPS-AE is a mode of 
therapy (Philips Respironics Inc, Monroeville, Pa) with potential advantages over the currently established 
modes of noninvasive positive pressure ventilation (CPAP and bi-level therapy).  This mode of therapy 
incorporates AVAPS (automated adjustable IPAP setting to maintain target ventilation with a settable rate 
of change), Auto EPAP and Auto Back up Rate.  It automatically adjusts EPAP in response to patient events 
such as snores, leaks, and apneas / hypopneas, provides an automatic back up rate and automatically adjusts 
pressure support in order to maintain the target tidal volume. In a prospective cohort study, Marin and 
colleagues have shown that positive airway pressure (PAP) therapy treatment for “COPD-OSA overlap 
syndrome” can reduce a composite index of hospitalizations and mortality (7). A prospective multi-center 
study of PAP therapy aimed at reducing re-hospitalization due to COPD has not been performed. 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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II. Study Design  
This is a multicenter, randomized, parallel-group, open label study of the efficacy of AVAPS-AE to prevent 
re-hospitalization in hospitalized patients with comorbid COPD. A wash-in period – aimed at assessing 
device tolerance – will be performed in order to exclude participants who are at high risk for discontinuing 
positive airway pressure (PAP) therapy. Similar to pharmaceutical studies, such a wash-in period for 
medication tolerance can help reduce attrition and missingness that can adversely affect study sample size 
estimations.   
 
Hospitalized patients with comorbid COPD who are at high risk for readmission will be recruited. 
Specifically patients with comorbid COPD who are to be discharged with (a) admission diagnosis of COPD 
(GOLD stage II or greater); AND (b) either a prior non-elective hospitalization (one in the past 12 months) 
OR active smoker. Such participants will undergo questionnaire-based screening for sleep-disordered 
breathing (STOP-BANG questionnaire) and if they have a high risk for SDB (> 3 points) will undergo an 
overnight portable sleep study for screening prior to hospital discharge (AHI > 10 per hour; >3% oxygen 
desaturation for hypopneas).  Sites may exercise the option of using the STOP-BANG questionnaire as a 
screening tool for the purposes of enriching the study population. 
 
Participants who exhibit AHI > 10 per hour; >3% oxygen desaturation for hypopneas based on the portable 
sleep test will undergo a PAP “wash in” daytime exposure for 30 minutes after adequate mask-fitting, on 
the therapy device (AVAPS- AE).  Participants who fail to tolerate such therapy, or indicate that they would 
be unable to use such therapy at night, will not be randomized. Considering the “wash-in” is performed 
prior to randomization, such participants will not be included as part of the intention to treat (ITT) analysis. 
 
After randomization and prior to discharge, participants will either be initiated on AVAPS-AE therapy 
(intervention arm) for 60 days or will be referred to the sleep center for further diagnostic testing and therapy 
initiation (standard of care arm). Participants will complete quality of life questionnaires (Functional 
outcomes of sleep questionnaire [FOSQ]) at baseline (in-person), and in 30 and 60 days (by mail) post 
discharge. If participants assigned to the intervention arm are discharged with home O2 therapy, the O2 will 
be entrained into the AVAPS-AE device for nighttime use. At time of hospital discharge, if participants in 
the intervention arm are not meeting conventional daytime and nighttime criteria for O2 therapy [(SpO2 
<88% in room air –day) (> 5 continuous minutes SpO2 < 88% - nighttime)], they will undergo AVAPS-
AE therapy alone.  
 
Over the first 30 days post discharge, participants in the intervention arm will receive 3 phone calls to 
promote PAP therapy and medication adherence. Participants in the standard of care (SOC) arm will also 
receive 3 phone calls to promote medication adherence over the first 30 days post discharge. On days 30 
and 60, all participants will receive a phone call to determine if they had been admitted to the hospital, or 
had an unplanned visit to a physician’s office or emergency room. Information regarding hospital 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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admission, diagnostic tests, medication changes, and procedures will be collected from all participants. 
Discharge summaries of re-hospitalizations and office or ER visits, as well as diagnostics tests and therapies 
received will be collected for measuring healthcare costs. 
 
Participants who enrolled in a registry (optional) for a 3 year follow-up will also be queried on a yearly 
basis regarding hospitalizations, cardiovascular events, and assessment of vital statistics in the National 
Death Index registry. The study will conclude when all randomized participants have been followed for a 
minimum of 60 days. An independent Data Safety and Monitoring Committee (DSMC) will monitor safety 
data on an ongoing basis and may recommend that the study be stopped earlier in case of safety concerns. 
No Interim efficacy analyses is planned. Ongoing DSMB review is planned to assess  device and/or safety 
related clinical events and adjudicate if applicable. This will be performed after 25%, 50% and 75% of 
target enrollment have been completed.  Participants will be followed for occurrence of death or 
hospitalization throughout the duration of the study for a minimum of 24 months after randomization. All 
death and hospitalization reports will be collected on an ongoing basis during the study and will be 
adjudicated by an adjudication committee consisting of three site investigators. 
 
AVAPS-AE is a mode of therapy (Philips Respironics Inc, Monroeville, Pa) with potential advantages 
over the currently established modes of non-invasive positive pressure ventilation (CPAP and bilevel 
therapy).  This mode of therapy incorporates AVAPS (automated adjustable IPAP setting to maintain 
target ventilation with a settable rate of change), Auto EPAP and Auto Back up Rate. We believe that 
these automated parameters will allow better nocturnal ventilatory control to offset the differing elastic 
and resistive loads imposed by changes in body position during sleep. Furthermore, AVAPS-AE will 
counter the changing ventilatory requirements due to alterations in lung volumes and airway resistance 
during different stages of sleep. In summary, the AVAPS-AE mode will enable automatic adjustment in 
response to ventilatory changes throughout the night.  The device platform used in this study with the 
AVAPS-AE feature is in the BiPAP A40 platform.  This device uses existing modes of therapy, therapy 
features, and algorithms as that which have been previously cleared by the Food and Drug Administration 
(FDA) (K121623).   
 
III. Study Objectives/Endpoints  
 
Specific aim #1: Evaluate the effects of novel application of Averaged Volume Assured Pressure Support 
(AVAPS-AE) therapy on time to (# of days) emergent and non-emergent healthcare utilization in patients 
with sleep-disordered breathing who are hospitalized with co-morbid COPD.  
 
Specific aim #2: Evaluate the effects of novel application of Averaged Volume Assured Pressure Support 
(AVAPS-AE) therapy on the number of emergent and non–emergent healthcare utilization over 6 months; 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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costs related to re-hospitalization; number of visits to physician offices or emergency rooms, and health-
related quality of life (disease-specific and general HR-QOL measures).  
 
Primary Endpoints 
Composite end-point of time to occurrence of emergent healthcare utilization (such as re-hospitalization, 
unscheduled physician office visits, urgent care visits or emergency room visits).  
 
Secondary Endpoints: 
1. Healthcare Costs  
2. Change in quality of life (SF-36) at 30 and 60-days 
3. Change in quality of life (FOSQ) at 30 and 60-days 
4. Number of hospitalizations over 3 years (optional if enrolled in registry) 
5. Time to re-hospitalization alone 
6. Composite end-point of time to occurrence of non-emergent healthcare utilization (such as  
scheduled hospitalization, scheduled physician office, urgent care visits or emergency room 
visits). 
 
IV. Subject Selection  
Inclusion criteria: 
1. Hospitalized patients who are at high risk for readmission who are at least 18 years of age.  
2. Specifically patients with (a) a primary or secondary admission diagnosis of COPD who are ready 
for discharge AND (b) are also found to have sleep-disordered breathing (AHI ≥ 10 per hour; >3% 
oxygen desaturation for hypopneas) by overnight portable respiratory study prior to hospital 
discharge. 
3. Bedside spirometry revealing evidence for obstructive lung disease (post-bronchodilator; GOLD 
stage II or greater (FEV1 <70% predicted post BD). 
4. No previous home PAP or NIV use within the past year 
 
Exclusion criteria: 
1. Central sleep apnea (Central apnea index >5 per hour; and/or >50% are central apneas & hypopneas) 
2. Clinically unstable, i.e., hypotensive shock, uncontrolled cardiac ischemia or arrhythmias, requiring life 
support ventilation or as otherwise determined by the investigator 
3. Participants with Stage III & IV Chronic Heart Failure as defined by the New York Heart Association 
(NYHA) Classification 
4. Known or expected contraindications for the use of non-invasive ventilation per the assessment of the 
investigator. 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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5. Lack of medical insurance 
 
V. Study Enrollment 
Participants who are screened for enrollment will be entered on a screening log which will be maintained 
at the clinical site.  Participants referred for screening will be given a thorough explanation of the study 
and the requirements for participation by the study coordinator or other qualified medical professional.  If 
the participant is interested in the study, the investigator or a member of his/her staff should approach the 
patient to obtain written informed consent.  The background of the proposed study, the benefits and risks 
of the procedures and study should be thoroughly explained to the participant.  The participant must sign 
the consent form prior to enrollment.  This form or a modification of it must have prior approval of the 
study site’s Institutional Review Board (IRB).  Failure to provide informed consent renders the participant 
ineligible for the study. 
 
Up to 10 sites will be recruiting for this study. Up to 80 participants will be enrolled across all sites with 
the goal of 60 participants (N=60) completing the study (25% attrition rate). One site should not enroll 
more than 25% of total N. 
 
VI. Study Procedures 
Screening Assessment 
Hospitalized patients with comorbid COPD who are at high risk for readmission will be recruited. 
Specifically patients with comorbid COPD who are about to be discharged. with (a) prior hospitalization 
(within the past 12 months) Such participants will undergo questionnaire-based screening for sleep-
disordered breathing (STOP-BANG questionnaire) and if they have a high risk for SDB (> 3 points) will 
undergo an overnight screening portable sleep study the night prior to hospital discharge (AHI > 10 per 
hour; >3% oxygen desaturation for hypopneas).  Sites may exercise the option of using the STOP-BANG 
questionnaire as a screening tool for the purposes of enriching the study population. 
 
Spirometry 
Each participant will undergo a spirometric assessment, using a handheld Koko TM unit, to determine if 
they meet inclusion criteria.    
Spirometry will be performed based on the “Standardization of Spirometry – 2005”. 11Acceptability and 
reproducibility criteria are summarized in Table 8 of the ATS document. Spirometry equipment must be 
calibrated with a 3L syringe prior to the first use daily.  The results will be printed and maintained in a 
calibration log, which will routinely be monitored for compliance during monitoring visits.  Spirometry 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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values recorded on the CRF will be post bronchodilator. Participants will need to reveal evidence for 
obstructive lung disease Gold stage II or greater (FEV1 < 70%) in order to continue in the study. 
 
 
Diagnostic Overnight Sleep Study 
Site investigators will make appropriate documentation in the study participants chart that they will be 
undergoing an overnight sleep study. In addition, results of the sleep study will be communicated to the 
participant by the site investigator and documented appropriately.  
 
Either an Alice Night One (Philips Respironics) will be used for the overnight diagnostic sleep study. The 
Alice devices are portable home sleep testing devices that records information about breathing.  It is used 
to diagnose OSA.  These devices may be used in a sleep lab or clinical setting by trained professionals, or 
it may be used at home by patients as directed by their health care provider. Participants who are found to 
have sleep disorder breathing (AHI ≥ 10 per hour) will qualify. It is known that supplemental oxygen that 
is titrated to maintain oxygen levels above 90% does not allow for easy differentiation of hypopneas. 
Therefore, for participants who require supplemental oxygen at night, oxygen will be titrated not to 
exceed 90% saturation at the start of the study on the night of the sleep test during calm wakefulness 
while lying in hospital bed at patient-determined head-elevation.    
 
During the diagnostic sleep study, participants will be set-up with on with the portable device that 
includes the following sensors: 
• An effort belt will be secured around the chest to measure movements associated with breathing 
effort 
• Nasal cannula 
• A flexible finger sensor placed on the finger to measure oxygen saturation (average signaling time 
of 3 seconds) and pulse 
 
 
 
Scoring 
• 
All sleep studies be scored by the automated Somnolyzer software program. Somnolyzer is a 
computer program intended for use as an aid for the diagnosis and treatment monitoring of sleep-
related respiratory disorders. Somnolyzer scores sleep stages, arousals, respiratory events and 
periodic limb movements in sleep according to published standards based on polysomnographic 
(PSG) recordings.    All sleep variables will be classified and scored using the 2007 AASM criteria. 9, 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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10, 11  All sleep studies will be initially interpreted by trained research staff in order to determine 
participant qualification  All studies will be centrally scored to verify enrollment criteria. Apneas will 
be scored according to AASM Scoring Manual rules VIII.3.A, B. 
• 
Hypopneas will be scored according to the AASM Scoring Manual rule VIII.4.A for desaturations 
(SpO2 >3%) with a nadir below 90% 
NOTE: If the portable sleep test yields less than 3 hours of total recording time, the participant will have 
the option of having the sleep test repeated. If the participant does not elect to repeat the sleep test or the 
repeat sleep test yields less than 3 hours of total recording time, the participant’s data will not be included 
in the statistical analysis at the end of the study.  Furthermore, a replacement participant will then be 
enrolled. An exception to when the minimum required recording time is < 3 hours is the following: when 
the total respiratory events (apneas and hypopneas) counted (in the actual recording time duration) is 
divided by 3 hours (rather than the actual recording time) results in an AHI of ≥ 10 per hour. 
 
 
PAP Wash- in Titration PSG 
Participants who exhibit AHI > 10 per hour; >3% oxygen desaturation for hypopneas based on the 
portable sleep test will undergo exposure for 30 minutes after adequate mask-fitting on the therapy device 
(AVAPS- AE; see device settings under section below entitled, “Standard Procedures and measurements 
prior to discharge”). Participants who fail to tolerate such therapy, or indicate that they would be unable to 
use such therapy at night, will not be randomized. Considering the “wash-in” is performed prior to 
randomization, such participants will not be included as part of the intention to treat (ITT) analysis.  
 
Participants that are placed on PAP therapy during admission and tolerate the therapy will not be 
subjected to this aspect of the trial. Their experience, during the hospital visit, with the therapy will count 
as the PAP Wash-In.  
 
Standard Procedures and measurements prior to discharge 
 
Room Air SpO2 assessment/Supplemental Oxygen 
A room air SpO2 measurement will be used to make a determination if supplemental oxygen is required 
prior to hospital discharge. SpO2 should be collected with the participant breathing room air for at least 15 
minutes prior. If participants cannot maintain a SpO2 of at least 90% on room air, supplemental oxygen 
will be prescribed.  If the participant requires supplemental oxygen (according to the guidelines stated 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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below), but was not previously prescribed supplemental oxygen, the study investigator will prescribe it 
for the participant. 
 
Data collection will consist of key demographic characteristics including gender, age, height, and weight. 
In addition, a medical history, physical exam, vital signs, medication assessment and Charlson co-
morbidity index will all be collected/obtained.  
 
Quality of Life Questionnaires  
Two different quality of life questionnaires will be used in this study. Quality of life questionnaires are 
important tools for measuring health status changes in participants receiving an intervention.  The general 
health questionnaire that measures functional health, well – being, and physical and mental health (SF-36) 
will be used in this study.  The disease specific quality of life questionnaire (Functional Outcome of Sleep 
Questionnaire, FOSQ) will also be used in this study.  Participants will be asked to complete these 
questionnaires prior to discharge.  
 
 
Randomization 
Following the completion of the screening procedures to determine study eligibility, participants will be 
randomly assigned to one of two study arms: 1) Intervention Group (AVAPS-AE), or 2) Standard of Care 
(SOC).  A randomization website will balance the therapy assignments within each of the three 
classifications of COPD severity:  Gold Stage 2, 3, and 4.  The research sites will attempt to balance 
recruitment between stage-3 and stage-4 patients; however, enrollment of stage-2 patients will be capped 
at 10, as this severity comprises a small proportion of the hospitalized patients with COPD.   
 
Intervention Group: 
AVAPS settings: 
• Target Tidal Volume   
 
8 ml/kg of ideal body weight 
• Pressure Support Min / Max  
4 / 26 cmH2O  
• Max Pressure  
 
 
30 cmH2O 
• EPAP Min / EPAP Max 
 
4 / 20 cmH2O  
• Rate 
 
 
 
 
Auto 
 
Participants in the intervention group will be sent home the AVAPS-AE therapy device. They will receive 
one on one training on the device as well as a user manual 
 
SOC Group: 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Standard of care: Portable sleep test results will be communicated to the participant and their health care 
provider. Timing and determination of further evaluation and treatment of the participant’s sleep 
disordered breathing will be per their participant’s health care provider’s usual care pathway.  Sites with 
change in usual care pathways that involve immediate initiation of PAP therapy as a standard practice will 
remain in the study. Such data will be analyzed in “per-protocol analysis”. Participants in the SOC arm 
will receive phone calls to promote medication adherence. 
 
Post Discharge Study period (60 days) 
• One week Device Adherence Assessment (Intervention Group) 
During the first 2-7 business days post discharge, research staff will evaluate participant’s device 
adherence via remote download. Participants with poor adherence to AVAPS-AE at home (adequate 
adherence defined as > 4 hours of use on at least 5 of the first 7 nights) will not be included in the “per-
protocol analysis” (Such participants will, however, be considered in the intention to treat analysis). Per 
the investigators discretion, the device setting parameters may be adjusted at this time.  
 
• Weekly Phone Follow-ups (Initial 30 days only): 
Phone calls will be made weekly (+ 2 business days) by the study coordinator to assess mask interface 
issues (Intervention group) and encourage adherence to AVAPS-AE (Intervention group) and medications 
(both intervention and SOC group). If participants require an additional visit related to issues noted above, 
this visit may occur either in the home or as an office to the study site. 
 
 
• Day 30 
 At 30 days (+ 2 business days) post discharge, participants in both Intervention and SOC groups will 
receive a phone call to determine if they had been admitted to this hospital, or had an unplanned visit to a 
physician’s office or emergency room.  Participants will be asked to complete FOSQ and SF-36 
questionnaires. Participants will be given the option of completing the questionnaires verbally via phone 
call or completing handwritten copies and returned via direct mail. Postage paid return envelopes will be 
provided to participants who elect to complete and return the surveys by mail.  
 
 
• Day 60 
On day 60 (+ 2 business days), participants in both Intervention and SOC groups will receive a phone call 
to determine if they had been admitted to this hospital, or had an unplanned visit to a physician’s office or 
emergency room. Participants will be asked to complete a final FOSQ and SF-36 questionnaire. 
Participants will be given the option of completing the questionnaires verbally via phone call or 
completing handwritten copies and returned via direct mail. Postage paid return envelopes will be 
provided to participants who elect to complete and return the surveys by mail. Participants in both 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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intervention and SOC groups will receive $150.00 as compensation for participating in the study. 
Compensation will be pro-rated based on completion of study milestones. 
 
Information regarding admission, diagnostic tests, medication changes, and procedures will be collected 
from all participants. Discharge summaries of re-hospitalizations and office or ER visits and diagnostics 
tests and therapies received will be collected for measuring healthcare costs.  
 
Participants will be asked if they would be interested enrolling in a registry for a 3 year follow-up. This 
will involve participants being contacted on a yearly basis inquiring about any hospitalizations, 
cardiovascular events, and assessment of vital statistics in the National Death Index registry. Participants 
who elect to enroll the registry will receive an additional $25 in compensation.  
 
 
Transition Plan: 
Upon completion of the study or earlier termination, site investigators will cooperate with the study 
participants’ primary health care providers regarding continuity of care to assure that participants receive 
appropriate follow-up care after the conclusion of the study. Study participants who are randomized to the 
treatment group, where a therapeutic benefit is evident, will be allowed to keep the provided AVAPS 
device until a similar replacement device can be provided to the participant through usual care pathways 
as part of this transition plan. Study participants who are randomized to the SOC group will have the 
option of receiving an AVAPS unit at the end of the 60 day period if prescribed and provided through the 
usual care pathway of their healthcare provider as part of this transition plan. The risk of additional and 
on-going device supplies not being covered by insurance or involving co-pays will be explained to the 
participant within the consent. Philips will not be responsible for providing device maintenance or study 
supplies after the 60 day study period.  
 
 
 
 
Study Process Flow: 
Study Procedures 
 
Hospital Procedures 
(Pre-Discharge) 
Post Discharge Study 
Procedures 
 
Post 60 Day Study 
Procedures 
 
Informed consent 
X 
 
 
Inclusion/Exclusion Review 
X 
 
 
Medical History Assessment 
X 
 
 
Vitals 
X 
 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Physical Exam 
X 
 
 
Medication Assessment 
X 
 
 
Bedside Spirometry 
X 
 
 
Room Air SpO2 assesment 
X 
 
 
Anthropometric measurements 
X 
 
 
Stop –Bang Questionnaire 
X 
 
 
20 minute PAP Wash-in 
X 
 
 
QOL questionnaires (FOSQ and 
SF-36) 
X 
X 
X 
Charleston Co-Morbidity Index 
X 
 
 
Overnight Portable Sleep Test 
X 
 
 
Randomization 
X 
 
 
 
Device Set up training/Mask 
fitting 
X 
 
 
1 week PAP adherence 
assessment (Treatment Group 
only) 
 
X 
 
Weekly phone calls to promote 
PAP and medication adherence 
 
X 
 
30 day Healthcare utilization 
assessment and questionnaire 
Phone Call  
 
 
X 
 
 
60 day Healthcare utilization 
assessment and questionnaire 
Phone call 
 
X 
 
Transition Plan 
 
 
X 
Optional Registry 
 
 
X 
 
 
 
VII. Statistical Analysis 
The method described by Cook and Lawless will be used to handle repeated hospitalizations, physician 
office visits, or emergency room visits in patients who may or may not also have a terminal event. All 
repeated hospitalizations that occur in patients will be counted. We will use the count-approach and the 
gap-time approach, described by Cook and Lawless because we are interested in studying event 
occurrence rates in the two groups as well as the time to occurrence of events. Analysis will be performed 
for both 30- and 60-days. Actuarial costs will be assessed in patients belonging to both the intervention 
and usual care arm. Unadjusted comparisons of these costs will be made by independent t-tests or non-
parametric equivalent.  Differences will be adjusted for potential confounders and other covariates in 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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multivariate regression models, to include age, gender, race, body mass index, baseline severity of COPD, 
AVAPS-AE and medication adherence. Biologically plausible effect modification will be evaluated 
before significant confounders are selected by inspection of significance levels as well as impact of 
estimated coefficient for hypothesis variable. 
 
Data and Safety Monitoring Plan: 
Each subject will be assigned an identifying number to maintain confidentiality.  Records will be stored in 
a database format that can be read by a standard statistical package.  The examination forms will be 
formatted to facilitate accurate data entry and editing, and programs will be written to allow range checks 
at entry with illegal values not accepted.  Specific missing codes will identify non-obtainable data due to 
missed visits or skipped questions.  The research coordinator will enter the data into the case report forms 
and the PI will proof read the forms.  Data will be entered weekly and cross-checked with the original 
data forms at the end of the week.  The data manager and the study coordinator will perform weekly data 
verification and protocol compliance checks. Case Report Forms will minimize data entry error.  
 
Safety monitoring plan: Adverse event reporting will be monitored in accordance with the guidelines and 
regulations of the governing IRB. Any serious and/or unanticipated problems will be reported 
immediately to the Institutional Review Board (IRB) and Philips-Respironics, Inc. as required. The site-PI 
and coordinator will monitor adherence to the protocol and data quality standards, and monitor for patient 
safety and evidence for adverse or beneficial effects.  The site-PI will prepare annual report for review by 
the IRB.  The reports will include: screening and baseline data, efficacy data, safety and adverse data, 
subject enrollment data, and dropout data (number, reason, and at what study phase).  
 
 
VII. Risks and Discomforts 
We believe that there are minimal risks to participating in this study.  Adverse effects of Non-Invasive 
(NPPV) are usually minor and manageable.  The masks may cause some discomfort and air pressure and 
flow have adverse effects.  All adverse effects encountered, including mask discomfort, nasal or mouth 
congestion or dryness, eye irritation, gastric insufflation, and nasal bridge ulceration will be recorded on 
data sheets that are part of the case report form.  NPPV has not been shown to cause sinusitis or 
bronchitis, but these will be recorded if they occur, as well.  Other more serious adverse effects, such as 
pneumothorax or aspiration pneumonia, are distinctly unusual in the outpatient setting, but will be 
recorded if they occur.  The risk of pneumothorax is rare, occurring in less than 1% of the participants.   
All adverse events will be reported the IRB annually and at the time of study closure. All significant 
adverse events will be reported to the Institutional Review Board within 24 hours. 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Discomfort is unusual during the lung function testing (spirometry); however, some participants can 
experience shortness of breath, lightheadedness, fainting, increased blood pressure or heart rate, coughing, 
wheezing or chest tightness after performing the test.  All testing will be conducted by a trained study 
staff 
 
The study equipment that will be used by the participant has been tested to ensure safety.  Should the 
AVAPS-AE device not perform as designed, ventilation could increase or decrease more than desired.  
This effect could be uncomfortable or awaken the participant.  Additionally, there will be weekly-up 
phone calls to ensure there are no issues with the therapy.  In the event there is an issue with either 
therapy, the participant can easily remove their interface device should it become uncomfortable or make 
breathing difficult.   
 
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of study medication, whether or not considered related to study medication.  
 
AEs will include:  
- 
Changes in the general condition of the patient  
- 
Subjective symptoms offered by or elicited from the patient;  
- 
Signs observed by the investigator or study personnel;  
 
All concurrent disease including any change in severity or frequency of pre-existing disease. 
A serious AE is one that:  
- 
Results in death 
- 
Is an immediate threat to life 
- 
Results in permanent disability 
 
In addition, a serious AE is one that is judged by the investigator to be an important or medically 
significant event. Causality assessments of AEs: For all AEs, the investigator will provide an assessment 
of causal relationship to study device. Appropriate forms will be used for this purpose and filed in the 
case report forms and submitted to the IRB for review. They will be classified as related, possibly related, 
and not related. The severity will be adjudged as being mild, moderate, or severe. Due to the complicated 
medical conditions of the patient population being recruited into the study, SAEs including 
hospitalizations are to be expected.  The expected 30 day Re-admission rate for the patient population 
enrolled in this study is 20.5 percent (4, 5). 
 
Discomfort is unusual during the lung function testing (spirometry); however, participants can experience 
shortness of breath, lightheadedness, fainting, increased blood pressure or heart rate, coughing, wheezing 
or chest tightness after performing the test. All testing will be conducted by a trained study staff. 
 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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Given the risks outlined, we believe that although there may be discomforts associated with the use of this 
device and study related procedures, the risks are minimal. 
 
VIII. Potential Benefits 
Although participation in this trial will not result in any direct benefit to the participant, they will be 
contributing to generalizable data that will help improve device design and function. 
 
IX. Monitoring and Quality Assurance 
This clinical study will be monitored by Philips Respironics Inc. (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, and to resolve any issues that 
arise during the conduct of the study.  The monitoring process includes initial site qualification, periodic 
visits to the site, and a final visit to the site once the study is complete.  Monitoring visits are scheduled 
periodically throughout the conduct of the study to assure compliance with the investigational plan, and to 
verify the completeness and accuracy of study data.  Monitoring also aids in identifying any research-
related problems for the sponsor and/or investigator to correct.  The Sponsor will conduct monitoring 
visits with appropriately trained clinical research professionals.  
 
X. Confidentiality 
Confidentiality of participant identification and test-related information is very important. The privacy 
rules and requirements according to governing regulations will be implemented. Methods to protect the 
privacy of participants and clinical information will be used. A unique identification number designed to 
protect the identity of participants will be used to identify the participant on report forms, recruitment 
logs, data forms or other reports containing information or referring to a participant. 

            
 
 
A Pilot, Multi-Center, Randomized, Open-Label, Parallel Group Study to Assess the Effects of a 
Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) 
therapy on Re-hospitalization in Patients with Sleep-Disordered Breathing with co-morbid COPD. 
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X. References 
1. 
Trends in Chronic bronchitis and emphysema. Morbidity and Mortality. . Part II ALA 
Epidemiological and Statistics unit Research and Program Services. May 2005. 
2. 
Trends in Chronic bronchitis and emphysema. Morbidity and Mortality. Part II. ALA 
Epidemiological and Statistics unit. Research and Program Services. 2005 May. 
3. 
http://www.lung.org/lung-disease/copd/resources/facts-figures/COPD-Fact-Sheet.html#Sources. 
2013;Last accessed March 12, 2014. 
4. 
Westert GP, Lagoe RJ, Keskimaki I, Leyland A, Murphy M. An international study of hospital 
readmissions and related utilization in Europe and the USA. Health policy (Amsterdam, Netherlands). 2002 
Sep;61(3):269-78. PubMed PMID: 12098520. Epub 2002/07/06. eng. 
5. 
Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-
service program. The New England journal of medicine. 2009 Apr 2;360(14):1418-28. PubMed PMID: 
19339721. Epub 2009/04/03. eng. 
6. 
Briones Claudett KH, Briones Claudett M, Chung Sang Wong M, Nuques Martinez A, Soto 
Espinoza R, Montalvo M, et al. Noninvasive mechanical ventilation with average volume assured pressure 
support (AVAPS) in patients with chronic obstructive pulmonary disease and hypercapnic encephalopathy. 
BMC pulmonary medicine. 2013;13:12. PubMed PMID: 23497021. Pubmed Central PMCID: 
PMC3637438. Epub 2013/03/19. eng. 
7. 
Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic 
obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. American journal of 
respiratory and critical care medicine. 2010 Aug 1;182(3):325-31. PubMed PMID: 20378728. Epub 
2010/04/10. eng. 
8.  Wittine LM1, Olson EJ2, Morgenthaler TI. Effect of recording duration on the diagnostic accuracy of 
out-of-center sleep testing for obstructive sleep apnea . Sleep. 2014 May 1;37(5):969-75. doi: 
10.5665/sleep.3672. 
9.  
Downey, Ralph III, PhD. Sleep Apnea. eMedicine Journal, March 13, 2002, Volume 3, Number 3. 
10.  
The Report of an American Academy of Sleep Medicine Task Force. Sleep-Related Breathing 
Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in 
Clinical Research. Sleep, Volume 22, No. 5, 1999 
11.  
Standardisation of Spirometry. ATS / ERS Task Force: Standardisation of Lung Function Testing, 
Eur Respir J 2005; 26: 319-338.19. Piper, A. J, D, Wang, B.J. Yee, et al. Randomised trial of CPAP vs. 
bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal 
desaturation. Thorax 2008 63: 395-401.