Pressure modification or humidification for improving usage ofcontinuous positive airway pressure machines in adults withobstructive sleep apnoea (Review)

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Cochrane Database of Systematic Reviews
Pressure modification or humidification for improving usage of

continuous positive airway pressure machines in adults with
obstructive sleep apnoea (Review)
Kennedy B, Lasserson TJ, Wozniak DR, Smith I
Kennedy B, Lasserson TJ, Wozniak DR, Smith I.

Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with
obstructive sleep apnoea.
Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No.: CD003531.
DOI: 10.1002/14651858.CD003531.pub4.
www.cochranelibrary.com
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in
adults with obstructive sleep apnoea (Review)
Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
HEADER......................................................................................................................................................................................................... 1
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 4
BACKGROUND.............................................................................................................................................................................................. 13
OBJECTIVES.................................................................................................................................................................................................. 13
METHODS..................................................................................................................................................................................................... 14
RESULTS........................................................................................................................................................................................................ 16
Figure 1.................................................................................................................................................................................................. 17
Figure 2.................................................................................................................................................................................................. 20
Figure 3.................................................................................................................................................................................................. 24
Figure 4.................................................................................................................................................................................................. 27
Figure 5.................................................................................................................................................................................................. 28
Figure 6.................................................................................................................................................................................................. 29
DISCUSSION.................................................................................................................................................................................................. 30
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 32
ACKNOWLEDGEMENTS................................................................................................................................................................................ 33
REFERENCES................................................................................................................................................................................................ 35
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 51
DATA AND ANALYSES.................................................................................................................................................................................... 143
Analysis 1.1. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 1 Machine usage (hours/night)............................................. 145
Analysis 1.2. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 2 Machine usage (hours/night) (Pepin imputed).................. 145
Analysis 1.3. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 3 Number of participants who used CPAP therapy > 4 hours 146
per night................................................................................................................................................................................................
Analysis 1.4. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 4 Machine usage (on nights when CPAP used 'effectively')..... 147
Analysis 1.5. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 5 Machine usage (frequency of usage as % of days)............. 147
Analysis 1.6. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 6 Machine usage (% of nights of > 4 hours of use) - cross- 147
over studies...........................................................................................................................................................................................
Analysis 1.7. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 7 Symptoms (Epworth Sleepiness Scale).............................. 148
Analysis 1.8. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 8 Withdrawals (parallel group trials/first arm cross-over 148
trials)......................................................................................................................................................................................................
Analysis 1.9. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 9 Quality of life (Functional Outcomes of Sleep 149
Questionnaire).......................................................................................................................................................................................
Analysis 1.10. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 10 Quality of life (Sleep Apnoea Quality of Life Index)........ 149
Analysis 1.11. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 11 Quality of life (SF-36 questionnaire)............................... 149
Analysis 1.12. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 12 Apnoea Hypopnoea Index (events/hr)........................... 151
Analysis 1.13. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 13 Arousals (events/hr)........................................................ 152
Analysis 1.14. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 14 Pressure of CPAP treatment (cmH2O)............................ 152
Analysis 1.15. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 15 Systolic blood pressure.................................................. 153
Analysis 1.16. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 16 Diastolic blood pressure................................................. 153
Analysis 1.17. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 17 24-hour mean BP............................................................ 153
Analysis 1.18. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 18 24-hour systolic BP.......................................................... 153
Analysis 1.19. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 19 24-hour diastolic BP........................................................ 154
Analysis 1.20. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 20 Diurnal mean BP............................................................. 154
Analysis 1.21. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 21 Diurnal systolic BP.......................................................... 154
Analysis 1.22. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 22 Diurnal diastolic BP......................................................... 155
Analysis 1.23. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 23 Nocturnal mean BP......................................................... 155
Analysis 1.24. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 24 Nocturnal systolic BP...................................................... 155
Analysis 1.25. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 25 Nocturnal diastolic BP.................................................... 155
Analysis 1.26. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 26 Tolerability outcomes..................................................... 156
Analysis 1.27. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 27 Patient preference (auto-CPAP/not auto-CPAP)............. 156
Analysis 2.1. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).................................................... 157
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive i
sleep apnoea (Review)
Informed decisions.
Analysis 2.2. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).................................... 158
Analysis 2.3. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross-over trials)..... 158
Analysis 2.4. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep Questionnaire)..... 158
Analysis 2.5. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 5 Quality of life (Sleep Apnoea Quality of Life Index).................. 158
Analysis 2.6. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 6 Quality of life (SF-36 questionnaire)......................................... 159
Analysis 2.7. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 7 Apnoea Hypopnoea Index (events/hr)...................................... 159
Analysis 2.8. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 8 Patient preference - BiPAP/no preference or CPAP................... 159
Analysis 2.9. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 9 Tolerability outcomes................................................................ 159
Analysis 2.10. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 10 Treatment comfort score...................................................... 160
Analysis 3.1. Comparison 3 CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night)................................................. 161
Analysis 3.2. Comparison 3 CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale)................................. 161
Analysis 3.3. Comparison 3 CPAPexp versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross-over 162
trials)......................................................................................................................................................................................................
Analysis 3.4. Comparison 3 CPAPexp versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep 162
Questionnaire).......................................................................................................................................................................................
Analysis 3.5. Comparison 3 CPAPexp versus fixed CPAP, Outcome 5 Quality of life (SF-36 questionnaire)...................................... 162
Analysis 3.6. Comparison 3 CPAPexp versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr).................................. 163
Analysis 3.7. Comparison 3 CPAPexp versus fixed CPAP, Outcome 7 Pressure of CPAP treatment (cmH2O)................................... 164
Analysis 3.8. Comparison 3 CPAPexp versus fixed CPAP, Outcome 8 Treatment satisfaction score................................................. 164
Analysis 3.9. Comparison 3 CPAPexp versus fixed CPAP, Outcome 9 Treatment comfort score....................................................... 164
Analysis 3.10. Comparison 3 CPAPexp versus fixed CPAP, Outcome 10 Treatment interface score.................................................. 164
Analysis 3.11. Comparison 3 CPAPexp versus fixed CPAP, Outcome 11 Preference.......................................................................... 164
Analysis 4.1. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 1 Machine usage (hours/ 165
night)......................................................................................................................................................................................................
Analysis 4.2. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 2 Symptoms (Epworth 166
Sleepiness Scale)...................................................................................................................................................................................
Analysis 4.3. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 3 Withdrawals (parallel group 166
trials/first arm cross-over trials)..........................................................................................................................................................
Analysis 4.4. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 4 Apnoea Hypopnoea Index 166
(events/hr).............................................................................................................................................................................................
Analysis 4.5. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 5 Quality of life (SF-36 167
questionnaire).......................................................................................................................................................................................
Analysis 4.6. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 6 Nasal symptoms (parallel 167
group trials)...........................................................................................................................................................................................
Analysis 4.7. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 7 Nasal symptoms (parallel 167
group trials)...........................................................................................................................................................................................
Analysis 4.8. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 8 Preference........................ 168
Analysis 5.1. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night)........................................ 169
Analysis 5.2. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale)........................ 169
Analysis 5.3. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross-over 169
trials)......................................................................................................................................................................................................
Analysis 5.4. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep 169
Questionnaire).......................................................................................................................................................................................
Analysis 5.5. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 5 Apnoea Hypopnoea Index (events/hr).......................... 170
Analysis 5.6. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 6 Pressure of CPAP treatment (cmH2O).......................... 170
Analysis 5.7. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 7 Systolic blood pressure................................................ 170
Analysis 5.8. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 8 Diastolic blood pressure............................................... 170
Analysis 6.1. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).............................................. 171
Analysis 6.2. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome 2 Number of participants who used CPAP therapy > 4 hours 171
per night................................................................................................................................................................................................
Analysis 6.3. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome 3 Quality of life (Functional Outcomes of Sleep 171
Questionnaire).......................................................................................................................................................................................
Analysis 7.1. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night)............................................ 172
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive ii
Informed decisions.
Analysis 7.2. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 2 Number of participants who used CPAP therapy > trialist 172
defined threshold..................................................................................................................................................................................
Analysis 7.3. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 3 Symptoms (Epworth Sleepiness Scale)............................ 172
Analysis 7.4. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 4 Withdrawals...................................................................... 173
Analysis 7.5. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 5 Quality of life (Functional Outcomes of Sleep 173
Questionnaire).......................................................................................................................................................................................
Analysis 7.6. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr)............................. 173
Analysis 8.1. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 1 Machine usage (hours/night)...... 174
Analysis 8.2. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness 174
Scale)......................................................................................................................................................................................................
Analysis 8.3. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 3 Quality of life (Functional 174
Outcomes of Sleep Questionnaire)......................................................................................................................................................
Analysis 8.4. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 4 Apnoea Hypopnoea Index 174
(events/hr).............................................................................................................................................................................................
Analysis 8.5. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 5 Mask leak.................................. 174
ADDITIONAL TABLES.................................................................................................................................................................................... 175
APPENDICES................................................................................................................................................................................................. 177
WHAT'S NEW................................................................................................................................................................................................. 181
HISTORY........................................................................................................................................................................................................ 182
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 182
DECLARATIONS OF INTEREST..................................................................................................................................................................... 182
SOURCES OF SUPPORT............................................................................................................................................................................... 183
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 183
INDEX TERMS............................................................................................................................................................................................... 184
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive iii
Informed decisions.
[Intervention Review]
Pressure modification or humidification for improving usage of

continuous positive airway pressure machines in adults with obstructive
sleep apnoea
Barry Kennedy1a, Toby J Lasserson2b, Dariusz R Wozniak3, Ian Smith3
1Department of Sleep Medicine, St. James's Hospital, Dublin, Ireland. 2Editorial & Methods Department, Cochrane Central Executive,
London, UK. 3Respiratory Support and Sleep Centre, Royal Papworth Hospital, Cambridge, UK
aThese authors contributed equally to this work. bThese authors contributed equally to this work
Contact address: Barry Kennedy, Department of Sleep Medicine, St. James's Hospital, Dublin, Ireland. bkennedy@stjames.ie.
Editorial group: Cochrane Airways Group.

Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 12, 2019.
Citation: Kennedy B, Lasserson TJ, Wozniak DR, Smith I. Pressure modification or humidification for improving usage of continuous
positive airway pressure machines in adults with obstructive sleep apnoea. Cochrane Database of Systematic Reviews 2019, Issue 12. Art.
No.: CD003531. DOI: 10.1002/14651858.CD003531.pub4.
ABSTRACT
Background
Obstructive sleep apnoea (OSA) is the repetitive closure of the upper airway during sleep. This results in disturbed sleep and excessive
daytime sleepiness. It is a risk factor for long-term cardiovascular morbidity. Continuous positive airway pressure (CPAP) machines can be
applied during sleep. They deliver air pressure by a nasal or oronasal mask to prevent the airway from closing, reducing sleep disturbance
and improving sleep quality. Some people find them difficult to tolerate because of high pressure levels and other symptoms such as a dry
mouth. Switching to machines that vary the level of air pressure required to reduce sleep disturbance could increase comfort and promote
more regular use. Humidification devices humidify the air that is delivered to the upper airway through the CPAP circuit. Humidification
may reduce dryness of the throat and mouth and thus improve CPAP tolerability. This updated Cochrane Review looks at modifying the
delivery of positive pressure and humidification on machine usage and other clinical outcomes in OSA.
Objectives
To determine the effects of positive pressure modification or humidification on increasing CPAP machine usage in adults with OSA.
Search methods
We searched Cochrane Airways Specialised Register and clinical trials registries on 15 October 2018.
Selection criteria
Randomised parallel group or cross-over trials in adults with OSA. We included studies that compared automatically adjusting CPAP
(auto-CPAP), bilevel positive airway pressure (bi-PAP), CPAP with expiratory pressure relief (CPAPexp), heated humidification plus fixed
CPAP, automatically adjusting CPAP with expiratory pressure relief, Bi-PAP with expiratory pressure relief, auto bi-PAP and CPAPexp with
wakefulness detection with fixed pressure setting.
Data collection and analysis

We used standard methods expected by Cochrane. We assessed the certainty of evidence using GRADE for the outcomes of machine usage,
symptoms (measured by the Epworth Sleepiness Scale (ESS)), Apnoea Hypopnoea Index (AHI), quality of life measured by Functional
Outcomes of Sleep Questionnaire (FOSQ), blood pressure, withdrawals and adverse events (e.g. nasal blockage or mask intolerance). The
main comparison of interest in the review is auto-CPAP versus fixed CPAP.
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive 1
Informed decisions.
Main results
We included 64 studies (3922 participants, 75% male). The main comparison of auto-CPAP with fixed CPAP is based on 36 studies with 2135
participants from Europe, USA, Hong Kong and Australia. The majority of studies recruited participants who were recently diagnosed with
OSA and had not used CPAP previously. They had excessive sleepiness (ESS: 13), severe sleep disturbance (AHI ranged from 22 to 59), and
average body mass index (BMI) of 35 kg/m2. Interventions were delivered at home and the duration of most studies was 12 weeks or less.
We judged that studies at high or unclear risk of bias likely influenced the effect of auto-CPAP on machine usage, symptoms, quality of life
and tolerability, but not for other outcomes.
Primary outcome
Compared with average usage of about five hours per night with fixed CPAP, people probably use auto-CPAP for 13 minutes longer per
night at about six weeks (mean difference (MD) 0.21 hours/night, 95% confidence interval (CI) 0.11 to 0.31; 31 studies, 1452 participants;
moderate-certainty evidence). We do not have enough data to determine whether auto-CPAP increases the number of people who use
machines for more than four hours per night compared with fixed CPAP (odds ratio (OR) 1.16, 95% CI 0.75 to 1.81; 2 studies, 346 participants;
low-certainty evidence).
Secondary outcomes
Auto-CPAP probably reduces daytime sleepiness compared with fixed CPAP at about six weeks by a small amount (MD -0.44 ESS units,
95% CI -0.72 to -0.16; 25 studies, 1285 participants; moderate-certainty evidence). AHI is slightly higher with auto-CPAP than with fixed
CPAP (MD 0.48 events per hour, 95% CI 0.16 to 0.80; 26 studies, 1256 participants; high-certainty evidence), although it fell with both
machine types from baseline values in the studies. Ten per cent of people in auto-CPAP and 11% in the fixed CPAP arms withdrew from the
studies (OR 0.90, 95% CI 0.64 to 1.27; moderate-certainty evidence). Auto-CPAP and fixed CPAP may have similar effects on quality of life, as
measured by the FOSQ but more evidence is needed to be confident in this result (MD 0.12, 95% CI -0.21 to 0.46; 3 studies, 352 participants;
low-certainty evidence). Two studies (353 participants) provided data on clinic-measured blood pressure. Auto-CPAP may be slightly less
effective at reducing diastolic blood pressure compared to fixed CPAP (MD 2.92 mmHg, 95% CI 1.06 to 4.77 mmHg; low-certainty evidence).
The two modalities of CPAP probably do not differ in their effects on systolic blood pressure (MD 1.87 mmHg, 95% CI -1.08 to 4.82; moderate-
certainty evidence). Nine studies (574 participants) provided information on adverse events such as nasal blockage, dry mouth, tolerance
of treatment pressure and mask leak. They used different scales to capture these outcomes and due to variation in the direction and size
of effect between the studies, the comparative effects on tolerability outcomes are uncertain (very low-certainty evidence).
The evidence base for other interventions is smaller, and does not provide sufficient information to determine whether there are important
differences between pressure modification strategies and fixed CPAP on machine usage outcomes, symptoms and quality of life. As with
the evidence for the auto-CPAP, adverse events are measured disparately.
Authors' conclusions
In adults with moderate to severe sleep apnoea starting positive airway pressure therapy, auto-CPAP probably increases machine usage
by about 13 minutes per night. The effects on daytime sleepiness scores with auto-CPAP are not clinically meaningful. AHI values are
slightly lower with fixed CPAP. Use of validated quality of life instruments in the studies to date has been limited, although where they
have been used the effect sizes have not exceeded proposed clinically important differences. The adoption of a standardised approach
to measuring tolerability would help decision-makers to balance benefits with harms from the different treatment options available. The
evidence available for other pressure modification strategies does not provide a reliable basis on which to draw firm conclusions. Future
studies should look at the effects of pressure modification devices and humidification in people who have already used CPAP but are
unable to persist with treatment.
PLAIN LANGUAGE SUMMARY
How does changing pressure in continuous positive airway pressure machines increase their usage by adults with sleep apnoea?
What is the aim of this review?
This review looks at different ways of helping people who have obstructive sleep apnoea (OSA) to use continuous positive airway pressure
(CPAP) machines. OSA refers to the temporary but frequent closing and opening of the throat during sleep. Because adults with OSA do
not get the sleep that they need, they can feel tired in the day and this impacts on their quality of life. They are at risk of falling asleep while
carrying out their daily activities and they are at risk of having heart disease or a stroke in the long term.
Key messages
Adults who use CPAP devices that automatically vary treatment pressure probably increase use of their machines by about 13 minutes
per night but it is unlikely that they will feel less tired compared with people who use fixed pressure CPAP machines. Fixed pressure CPAP
is slightly better at reducing the number of episodes where the airway closes at night. We need more information to be able to assess
whether there are important differences between these machines on quality of life and tolerability.
Informed decisions.
What was studied in this review?
CPAP machines are worn over the nose and mouth as people sleep at night. They blow air at a fixed pressure through the nose and mouth
to keep the airway open. This makes refreshing sleep easier to achieve, but some people find the machines difficult to use regularly. They
can find the level of pressure too high or they have a dry mouth when they wake up. If the pressure needed to keep the airway open is
lower, the machines could be easier to use more often.
We looked for studies that compared different ways of varying the way that pressure is delivered. We have focused on studies that compared
CPAP machines that automatically vary treatment pressure as the person sleeps (e.g. auto-CPAP) with machines that deliver pressure at
the same level throughout the night (fixed pressure CPAP).
What are the main results of the review?
We found 64 studies in 3922 people. Thirty-six studies in 2135 people were relevant to the comparison of auto-CPAP and fixed pressure
CPAP. The studies were from Europe, USA, Hong Kong and Australia. Seventy-five per cent of people recruited to the studies were men who
were recently diagnosed with sleep apnoea and had no experience of using CPAP.
Compared with fixed pressure CPAP, people starting treatment with auto-CPAP will probably use their machine by about 13 minutes more
per night at around six weeks (moderate-certainty evidence), although when we looked at the number of people who use the machines
for more than four hours per night, we did not have enough information to know whether there was a difference between the different
machines (low-certainty evidence).
Auto-CPAP probably reduces daytime symptoms by a small amount compared with fixed pressure CPAP (moderate-certainty evidence). A
similar number of people withdrew from the studies: 11% in fixed pressure CPAP and 10% with auto-CPAP (moderate-certainty evidence).
Both machines reduced the number of times that the upper airway closed during sleep, although fixed pressure CPAP was slightly
better (high-certainty evidence). Three studies used a scale that we chose as the most relevant one to measure quality of life in sleep
apnoea (the Functional Outcomes of Sleep Questionnaire). In people using the machines, the average difference between the devices on
this scale was small, but there was not enough evidence to be confident about this result (low-certainty evidence). Auto-CPAP may be less
successful in controlling blood pressure than fixed pressure CPAP, but more studies are needed to confirm this result. We are uncertain
as to how people found using their devices because information on tolerability (blocked nose, dry mouth, mask leak or feeling that the
pressure level was too high) was measured differently across the studies (very low-certainty).
This Plain Language Summary is current to October 2018
Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive
SUMMARY OF FINDINGS
Summary of findings for the main comparison. Auto-CPAP compared to fixed CPAP for sleep apnoea in adults
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Auto-CPAP compared to fixed CPAP for adults with a diagnosis of OSA
Patient or population: adults with a diagnosis of OSA

Setting: Europe, USA, Australia and Hong Kong
Intervention: automatically titrating CPAP
Better health.
Informed decisions.
Trusted evidence.
Comparison: fixed CPAP
Outcomes Anticipated absolute effects* (95% CI) Relative № of Certain- Com-

effect partici- ty of ments
Average effect or risk with fixed Average effect or risk with auto-CPAP (95% pants the evi-
CPAP CI) (stud- dence
ies) (GRADE)
Average machine usage (hours per Average nightly machine usage 5 0.21 hours per person per night longer - 1452 ⊕⊕⊕⊝
night) hours per night across all CPAP arms (0.11 longer to 0.31 longer) (31 Moder-
RCTs) ate1
Median follow-up: 6 weeks The average effect is about 13 minutes
longer per person per night (6 minutes to
20 minutes)
Number of participants using ma- Study population OR 1.16 346 ⊕⊕⊝⊝

chine for 4 or more hours per night Low1,2
601 per 1000 636 per 1000 (0.75 to (2 RCTs)
Follow-up: range 3 to 16 weeks 1.81)
(530 to 732)
Symptoms assessed with ESS from Average symptom scores ranged from 0.44 ESS units lower - 1285 ⊕⊕⊕⊝ MCID of
0 to 24 4.1 to 8.6 on the ESS (0.72 lower to 0.16 lower) (25 Moder- between
RCTs) ate1 2 to 3

Median follow-up: 6 weeks has been
pro-
posed
by Patel
2018.
Withdrawals (parallel group tri- Study population OR 0.90 1275 ⊕⊕⊕⊝

als/first arm cross-over trials) (0.64 to (13 Moder-
110 per 1000 100 per 1000 1.27) RCTs) ate 2
Median follow-up: 6 weeks (74 to 136)
4
Quality of life assessed with FOSQ The mean quality of life score was 5.58 0.12 FOSQ units higher - 352 ⊕⊕⊝⊝ MCID for
scale from 5 to 20 on the FOSQ (0.21 lower to 0.46 higher) (3 RCTs) Low1,3 FOSQ
has not
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Follow-up: range 4 to 104 weeks been
con-
firmed; a
change
of 1 unit
has been
pro-
Better health.
Informed decisions.
Trusted evidence.
posed
as repre-
senting a
possible
mean-
ingful
change
(Billings
2014).
AHI measured by number of Average AHI ranged from 2 to 9 events 0.48 events per hour higher - 1256 ⊕⊕⊕⊕
events/hr per hour (0.16 higher to 0.80 higher) (26 High 4
RCTs)
Median follow-up: 6 weeks
Blood pressure (mmHg) Systolic blood pressure - 353 ⊕⊕⊕⊝

(2 RCTs) Moder-
Follow-up 12 and 16 weeks The mean systolic blood pressure was 1.87 mmHg higher ate 5
133 mmHg (1.08 lower to 4.82 higher)
Diastolic blood pressure - 353 ⊕⊕⊝⊝

(2 RCTs) Low 6
The mean diastolic blood pressure was 2.92 mmHg higher
78 mmHg (1.06 higher to 4.77 higher)

Adverse events (machine tolerabili- Nine studies provided information on tolerability outcomes, but data could not - 574 ⊕⊝⊝⊝
ty outcomes) be combined because they were measured and analysed inconsistently across the (9 RCTs) Very low
studies. 7
Follow-up: 4 to 36 weeks
Studies used different scales and data to report on four main outcome types: nasal
blockage, dry mouth, tolerance of treatment pressure and mask leak. The direction
and size of effect varied between the studies across the outcomes.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention
(and its 95% CI).
5
AHI: Apnoea Hypopnoea Index; CI: confidence interval; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep
Questionnaire; MCID: minimal clinically important difference; mmHg: millimetres of mercury (used to measure pressure); OR: odds ratio; OSA: obstructive sleep apnoea;
RCT: randomised controlled trial.
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GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Better health.
Informed decisions.
Trusted evidence.
1 Downgraded one level due to serious risk of bias. All studies contributing data to machine usage were judged to be at unclear or high risk of bias for performance or attrition bias.
2 Downgraded one level due to serious imprecision. Wide confidence intervals include appreciable increase and slight reduction in effect.
3 Downgraded one level due to serious imprecision. Three studies contribute to the analysis with 352 participants. We believe that more trial data are needed to confirm the
lack of a difference in quality of life scores.
4 We did not downgrade for inconsistency which was due to a single outlying result. Incorporating between study variation with random-effects model did not change our
interpretation of the effect (0.21 versus 0.33 events per hour).
5 Downgraded one level due to serious imprecision. Confidence interval includes small decrease and increase in BP with auto-CPAP.
6 Downgraded two levels due to very serious inconsistency. We decided to downgrade twice for inconsistency in view of the discordant results between the studies and the likely
impact this has on the confidence interval.
7 Downgraded one level due to serious risk of bias, inconsistency and imprecision. Most studies judged to have unclear or high risk of performance and detection bias, variation
in reporting of data prevented meta-analysis and many studies had small sample sizes.
Summary of findings 2. Bi-PAP compared to fixed CPAP for sleep apnoea in adults
Bi-PAP compared to fixed CPAP for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea
Patient or population: adults with a diagnosis of sleep apnoea

Setting: Europe and USA
Intervention: Bi-PAP

Risk with fixed CPAP Risk with Bi-PAP (95% pants the evi-
CI) (stud- dence
ies) (GRADE)
Machine usage (hours/night) Average nightly machine usage 5.5 hours 0.14 hours/night higher - 268 ⊕⊕⊝⊝
per night across CPAP (0.17 lower to 0.45 higher) (4 RCTs) Low 1 2
Machine usage - - - - -
6
assessed by number of partici-
pants using machine for 4 or more
hours per night - not measured
Library
Cochrane
Symptoms assessed with ESS from The mean symptoms ranged from 8 to 11 0.49 ESS units lower (1.46 lower to - 226 ⊕⊕⊝⊝ MCID of
0 to 24 ESS units 0.48 higher) (4 RCTs) Low 1 3 between
2 to 3
Follow-up: 4 to 12 weeks has been
pro-
posed
Better health.
Informed decisions.
Trusted evidence.
by Patel
2018.
Withdrawals (parallel group tri- Study population OR 0.55 261 ⊕⊕⊝⊝

als/first arm cross-over trials) (0.26 to (3 RCTs) Low 3 4
188 per 1000 113 per 1000 1.17)
(57 to 213)
Quality of life assessed with FOSQ: Mean change from baseline 5.1 units 0.8 FOSQ units lower (6.08 lower to - 151 ⊕⊕⊝⊝ MCID for
scale from 5 to 20 4.48 units higher) Low 3 5 FOSQ
(1 RCT) has not
Follow-up: 8 weeks been
con-
firmed; a
change
of 1 unit
has been
pro-
posed
as repre-
senting a
possible
mean-

ingful
change
(Billings
2014).
AHI measured with number of The mean AHI was 6.6 events/hour 1.36 events/hour lower - 179 ⊕⊕⊝⊝
events/hr (6.92 lower to 9.63 higher) (2 RCTs) Low 6
Blood pressure - not measured - - - - -

7
Adverse events (machine tolerabili- Five studies provided information on tolerability outcomes but data could not be - 239 ⊕⊝⊝⊝
ty outcomes) combined because they were measured and analysed inconsistently across the (5 RCTs) Very low
studies. 17
Library
Cochrane
One study (N = 62) reported 5 withdrawals in CPAP group due to mask discomfort or
device intolerance. 20 participants across both arms complained of nasal dryness. 1
trial (N = 151) reported similar rates of dry mouth (4.2% and 7.5%) and mask intoler-
ance (11% and 10%) in Bi-PAP and CPAP groups, respectively.
Two small studies (N = 46) reported non-specific adverse events. One reported that
Better health.
Informed decisions.
Trusted evidence.
telephone contact did not identify the need for further interventions, and the other
that there were similar rates of non-specific adverse events.
One study (N = 28) used a global treatment comfort score on a 0 to 00 VAS. There was
insufficient evidence to determine whether Bi-PAP improved comfort scores (69 ver-
sus fixed CPAP 60, P = 0.16).
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and
its 95% CI).
AHI: Apnoea Hypopnoea Index; Bi-PAP: bilevel positive airway pressure; CI: confidence interval; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale;
FOSQ: Functional Outcomes of Sleep Questionnaire; MCID: minimal clinically important difference; OR: odds ratio; RCT: randomised controlled trial; VAS: visual analogue
scale

1 Downgraded one level due to serious risk of bias. Open-label design from one study and insufficient detail available to assess blinding and allocation process in other studies.
2 Downgraded one level due to serious imprecision. Wide confidence interval including higher average usage with either device.

3 Downgraded one level due to serious imprecision. Wide confidence interval.
4 Downgraded one level due to serious risk of bias. Lack of detailed description of randomisation process and lack of blinding in two studies contributing data to the analysis.
5 Downgraded one level due to risk of bias. Single study at high risk of bias from lack of blinding.
6 Downgraded two levels due to very serious imprecision. Wide confidence interval and small sample size.
7 Downgraded due to very serious inconsistency. Variation in the measurement of tolerability across the studies meant that no data could be combined,
Summary of findings 3. CPAP with expiratory pressure relief compared to fixed CPAP for adults with obstructive sleep apnoea
CPAP with expiratory pressure relief compared to fixed CPAP for improving usage of CPAP machines in adults with obstructive sleep apnoea

8
Setting: Europe, USA, New Zealand
Intervention: CPAP with expiratory pressure relief
Library
Cochrane
Outcomes Anticipated absolute effects* (95% CI) Relative № of Certain- Comments
effect partici- ty of
Risk with fixed CPAP Risk with CPAP with expiratory pres- (95% pants the evi-
sure relief CI) (stud- dence
ies) (GRADE)
Better health.
Informed decisions.
Trusted evidence.
Machine usage The mean machine usage was MD 0.14 hours/night higher - 609 ⊕⊕⊝⊝
assessed by hours/night 5.1 hours/night (0.07 lower to 0.35 higher) (9 RCTs) Low 1 2
Follow-up: range 2 to 24 weeks
Machine usage assessed by number of - - - - -

participants using machine for 4 or more
Symptoms The mean symptoms was 7 ESS 0.17 ESS units higher - 515 ⊕⊕⊕⊝ MCID of be-
assessed with ESS (0.26 lower to 0.60 higher) (6 RCTs) Moder- tween 2 to
ate 1 3 has been
Follow-up: range 4 to 24 weeks proposed by
Patel 2018.
Withdrawals (parallel group trials/first Study population OR 0.86 298 ⊕⊕⊝⊝

arm cross-over trials) (0.48 to (2 RCTs) Low 3
201 per 1000 178 per 1000 1.55)
Follow-up: 12 weeks (108 to 281)
Quality of life assessed with FOSQ: scale The mean quality of life was 0.4 FOSQ units lower - 74 ⊕⊕⊝⊝ MCID for
from 5 to 20 18.7 FOSQ units (1.15 lower to 0.35 higher) (1 RCT) Low 4 FOSQ has
not been
Follow-up: 12 weeks confirmed;

a change
of 1 unit
has been
proposed
as repre-
senting a
possible
meaning-
ful change
(Billings
2014).
9
AHI measured by number of events/hr The mean AHI was 5.3 events/ 0.24 events/hour higher - 342 ⊕⊕⊕⊕
hour (0.49 lower to 0.96 higher) (5 RCTs) High
Follow-up: range 6 to 12 weeks
Library
Cochrane
Adverse events (machine tolerability No specific measures of nasal or oral symptoms were carried out in six stud- - 577 ⊕⊝⊝⊝
outcomes) ies providing information on tolerability outcomes. Very
(6 RCTs) low 5 6
Follow-up: range 4 to 24 weeks Four studies assessed treatment comfort scores but data could not be com-
Better health.
Informed decisions.
Trusted evidence.
bined. None of the studies reported that there were differences between
the different treatment modes. Different measures of mask leak were made
by two studies with no differences reported in either 90th percentile leak or
average leak.
its 95% CI).
Questionnaire; MCID: minimal clinically important difference; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial.

1 Downgraded one level due to serious risk of bias. Uncertainty over study design from trials published as abstracts and open-label design in other studies.
2 Downgraded one level due to serious imprecision. Confidence interval includes no difference and increase of up to 20 minutes per person per night.
3 Downgraded two levels due to very serious imprecision. Wide confidence intervals and small sample size.
4 Downgraded two levels due to very serious imprecision. Single study with small sample size.
5 Downgraded one level due to serious imprecision. Small sample size.

6 Downgraded two levels due to very serious inconsistency. Different study designs and approaches taken to capturing tolerability outcomes.
Summary of findings 4. Heated humidification + fixed CPAP compared to fixed CPAP alone in adults with obstructive sleep apnoea
Heated humidification + fixed CPAP compared to fixed CPAP alone for improving usage of CPAP machines in adults with obstructive sleep apnoea

Setting: Europe, Australia, New Zealand and Thailand
Intervention: heated humidification + fixed CPAP
Comparison: fixed CPAP alone
10
Risk with fixed Risk with heated humidifi- (95% pants the evi-
Library
Cochrane
CPAP alone cation + fixed CPAP CI) (stud- dence
ies) (GRADE)
Machine usage The mean machine MD 0.37 hours higher - 277 ⊕⊕⊝⊝
assessed by hours per night usage was 5 hours (0.10 higher to 0.64 higher) (6 RCTs) Low 1 2
Follow-up: range 3 weeks to 12 weeks
Better health.
Informed decisions.
Trusted evidence.
Machine usage - - - - -
assessed by number of participants using machine for 4 or more

Symptoms The mean symp- MD 0.34 ESS lower - 184 ⊕⊕⊝⊝

assessed with ESS toms ranged from 4 (0.93 lower to 0.26 higher) (4 RCTs) Low 3 4
to 9 ESS
Follow-up: range 3 weeks to 12 weeks
Withdrawals (parallel group trials/first arm cross-over trials) Study population OR 1.00 316 ⊕⊝⊝⊝
(0.45 to (3 RCTs) Very low
Follow-up: median 12 weeks 159 per 1000 159 per 1000 2.24) 35
(78 to 297)
Quality of life assessed with FOSQ: scale from 5 to 20 - - - - -
- not measured
AHI measured by number of events/hr The mean AHI MD 0.3 events/hr higher - 44 ⊕⊕⊝⊝
(events/hr) was 4.2 (0.95 lower to 1.55 higher) (1 RCT) Low 5
Follow-up: 4 weeks events/hr

Adverse events (machine tolerability outcomes) Study population OR 0.32 147 ⊕⊕⊝⊝ This out-
assessed as number of participants experiencing a blocked nose (0.16 to (2 RCTs) Low 6 come
648 per 1000 371 per 1000 0.63) was se-
Follow-up: mean 4 weeks (227 to 537) lected
from dif-
ferent
mea-
sures of
nasal
11
symp-
toms.
Library
Cochrane
its 95% CI).
Questionnaire; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial.
Better health.
Informed decisions.
Trusted evidence.
1 Downgraded one level due to serious risk of bias. Open-label study design in a number of studies and lack of detail regarding methods of allocation.
2 Downgraded one level due to serious imprecision. The sample size of 277 may be sufficient for effect size observed, but confirmatory studies would help to establish this more
reliably.
3 Downgraded one level due to serious risk of bias, lack of blinding in one trial
4 Downgraded one level due to serious imprecision. Given baseline values and the change in both groups from using CPAP, the confidence interval includes a potentially meaningful
difference of 1 unit on the ESS.
5 Downgraded two levels due to imprecision: small sample size and wide confidence intervals
6 Downgraded two levels due to very serious imprecision. Sample size across the studies is small. There were a number of different measures of nasal symptoms and the effect
observed here may reflect multiplicity.

12
Informed decisions.
BACKGROUND Pressure modification devices adjust airway pressure according to

changes in airway resistance or the respiratory cycle. Automatically
Description of the condition adjusting positive airway pressure (auto-CPAP), bilevel positive
airway pressure (bi-PAP) or CPAP with expiratory pressure relief
Obstructive sleep apnoea (OSA) arises from recurrent episodes of
(CPAPexp) are modalities of pressure modification. Auto-CPAP
pharyngeal collapse during sleep. It disrupts sleep architecture,
devices analyse inspiratory flow and titrate the airway pressure
ventilation and cardiovascular homeostasis (Eckert 2008; Kasai
accordingly to maintain a constant airflow; thus, when airway
2012). As these episodes recur over time, adults with OSA
resistance decreases (i.e. sleeping in lateral position or after weight
experience fragmented and poor quality sleep. They report
loss), these devices reduce the pressure applied to the airway. In bi-
excessive daytime sleepiness, mood alterations as well as impaired
PAP devices, a higher pressure is applied to the airway throughout
cognition and memory (Gagnon 2014; Karimi 2015). Repetitive
the inspiratory phase and a lower pressure is applied throughout
hypoxaemia is associated with increased risk of cardiovascular
expiration. In CPAPexp there is a decrease in airway pressure
and cerebrovascular events (Shahar 2001; Yaggi 2005; Young
for a portion of the expiratory phase (Ryden 2014; Brown 2017;
2008; Redline 2010; Drager 2011). OSA frequently coexists with
Freedman 2017).
systemic hypertension and, in some people, contributes to its
development (Konecny 2014; Pépin 2014). Other consequences of Manufacturers have also combined multiple modalities of pressure
untreated OSA include increased risk of motor vehicle accidents, modification into a single device e.g. auto-CPAP combined with
higher prevalence of depression and reduced productivity at expiratory relief or bi-PAP with an automatic titration mechanism
work (Tregear 2009; Jordan 2014; Hirsch Allen 2015; Karimi 2015; (auto-CPAP combined with bi-PAP). These multimodality devices
BaHammam 2016). may have additive benefits on comfort compared to single modality
devices.
Description of the intervention
The main treatment of choice for OSA is continuous positive Humidification devices humidify the air that is delivered to the
airway pressure (CPAP). CPAP devices apply positive pressure to upper airway through the CPAP circuit.
the upper airway and prevent pharyngeal collapse. Consistent
How the intervention might work
use of CPAP improves physiological parameters of sleep, reduces
daytime sleepiness, enhances cognition and reduces motor vehicle Pressure modification interventions are designed to vary and
accidents (Giles 2006; Karimi 2015). Adults with OSA are advised to achieve the necessary pressure to maintain airway patency through
use CPAP for a minimum of four hours per night; research indicates the night. This has the potential to deliver the same effect on
that four hours is the threshold at which symptoms of daytime sleep disruption and symptoms but at a lower treatment pressure.
sleepiness resolve (Weaver 2007). By this mechanism of action, a reduction in mean pressure could
minimise local side effects of CPAP, improve tolerance and increase
Longitudinal studies also indicate that CPAP lowers the associated usage. Bi-PAP and C-Flex are also designed to lower
cardiovascular burden of OSA in people who are compliant with expiratory pressure and reduce the expiratory work of breathing,
it (Doherty 2005; Marin 2005; Martínez-García 2012; Myhill 2012). thereby increasing comfort. Adding humidification to the delivery
However, evidence from randomised studies of a beneficial effect of pressure in the airway might decrease side effects in the upper
of CPAP on cardiovascular outcomes is weak. This may be partly airway due to cold, dry airflow. Rather than change the pressure,
related to low adherence to CPAP in these studies; in the majority humidity makes the pressured air delivered to the airway less
of randomised controlled trials (RCTs) included in a recent meta- likely to cause dry mouth or throat, which could improve the
analysis, the average CPAP usage was < 4 hours/night (McEvoy 2016; tolerability of CPAP. Table 1 outlines the details of each device and
Yu 2017). Early seminal studies had indicated that people who use its associated mechanism.
CPAP for at least four hours per night obtain symptomatic benefit
and, subsequently, this threshold was accepted in research studies Why it is important to do this review
and clinical practice as a threshold likely to meet a key goal of
therapy (Kribbs 1993; Engleman 1994; Reeves Hoche 1994). The prevalence and economic costs of OSA are likely to increase
as levels of obesity increase globally (Peppard 2013; Garvey
Despite the benefits associated with treatment, usage of CPAP 2015; Sanna 2018). Establishing the evidence base for different
is often low. Estimates of people who use CPAP regularly in types of positive pressure therapy devices will help to inform
the long term vary, but range between 29% and 85% (Pépin decisions aimed at reducing the health burden of poorly treated
1999; Weaver 2010; Rotenberg 2016; Libman 2017). Tolerating OSA. Cognitive behavioural therapy, education and increasing
treatment with CPAP is a highly complex issue and determined engagement between the patient and CPAP provider have recently
by a number of factors. Disease severity, symptom relief from been shown to increase machine use (Wozniak 2014). The last
CPAP, underlying neurological disease or nasal anatomy play a role version of this review was published in 2009 (Smith 2009a), and we
alongside psychological factors, such as locus of control, anxiety decided to update the review in light of a number of studies that
and depression (Wild 2004; Broström 2010a; Catcheside 2010). have been published since we last assessed the evidence in this
Finally, device-related factors such as mask leak, skin abrasions and area.
nasal congestion may deter use (Bollig 2010; Wickwire 2013).
OBJECTIVES
Making the CPAP device more comfortable to use could also
increase compliance. This could be achieved by varying the To determine the effects of positive pressure modification or
delivered airway pressure at the point of inhalation and exhalation, humidification on increasing CPAP machine usage in adults with
or by humidifying the CPAP circuit. OSA.
Informed decisions.
METHODS Data for this outcome could be measured as mean differences

(MDs) in hourly use per participant per night or as the number of
Criteria for considering studies for this review participants who used machines for more than four hours per night.
Types of studies Secondary outcomes
We included randomised controlled trials (RCTs) of either parallel 1. Symptom scores (such as the Epworth Sleepiness Scale (ESS),
group or cross-over design. We included blinded and unblinded Stanford Sleepiness Scale (SSS) and nasal symptoms)
studies.
2. Withdrawals
Types of participants 3. Quality of life or Health Status (such as the Functional Outcomes
of Sleep Questionnaire (FOSQ) and Sleep Apnoea Quality of Life
We included trials involving adults of either sex with a diagnosis Index (SAQLI) scores. We analysed data from the Short-Form 36
of obstructive sleep apnoea (OSA), based on history and results (SF-36) but we did not use it as the basis for the 'Summary of
of sleep studies. The sleep studies were either oximetry studies findings' tables)
showing desaturation index (DI) of at least 5 per hour or of
4. Sleep disruption outcomes (Apnoea Hypopnoea Index (AHI) and
respiratory movements and airflow to give an Apnoea Hypopnoea
arousals)
Index (AHI) of at least 5 per hour.
5. Treatment pressure (for auto-CPAP)
We excluded trials assessing interventions in people with central 6. Blood pressure outcomes
sleep apnoea and where sleep apnoea was related to sleeping 7. Adverse events (most commonly measured as tolerability of
position. treatment pressure, mask leak and nasal or oral symptoms)
Types of interventions 8. Expression of preference (from cross-over studies)
We included the following comparisons. For the comparison of humidification and CPAP versus CPAP alone,
we considered nasal symptoms as an additional outcome. This
1. Automatically adjusting CPAP continuous positive airway was intended to capture the effects of humidity directly where the
pressure (auto-CPAP) including forced oscillation technique mechanism of action is targeted.
versus fixed pressure setting CPAP (fixed CPAP).
2. Bilevel positive airway pressure (Bi-PAP) versus fixed CPAP. Search methods for identification of studies
3. Continuous positive airway pressure with expiratory pressure Electronic searches
relief (CPAPexp) versus fixed CPAP.
The previously published version of this review included searches
4. Heated humidification plus fixed CPAP versus fixed CPAP alone.
up to September 2008 (Smith 2009a). The search period for this
5. Automatically adjusting CPAP with expiratory pressure relief update is September 2008 to October 2018.
(auto-CPAPexp) versus fixed CPAP.
6. Bi-PAP with expiratory pressure relief (Bi-PAPexp) versus fixed We identified studies from Cochrane Airways Trials Register
CPAP (Cochrane Airways 2019), which is maintained by the Information
7. Automatically adjusting Bi-PAP (auto Bi-PAP) versus fixed CPAP. Specialist for the Group. The Cochrane Airways Trials Register
contains studies identified from several sources:
8. CPAPexp with wakefulness detection versus fixed CPAP.
1. monthly searches of the Cochrane Central Register of Controlled
We excluded studies that were conducted as short-term laboratory-
Trials (CENTRAL), through the Cochrane Register of Studie (CRS);
based interventions, since they did not intend to capture the effects
of interventions administered on a nightly basis at home. We 2. weekly searches of MEDLINE Ovid SP 1946 to date;
excluded studies that were less than two weeks in duration because 3. weekly searches of Embase Ovid SP 1974 to date;
we were primarily interested in the effects of pressure modification 4. monthly searches of PsycINFO Ovid SP 1967 to date;
in the context of ongoing use of CPAP. 5. monthly searches of CINAHL EBSCO (Cumulative Index to
Nursing and Allied Health Literature) 1937 to date;
The effects of educational and behavioural interventions are now
considered in a different review (Wozniak 2014). 6. handsearches of the proceedings of major respiratory
conferences.
Types of outcome measures
Studies contained in the Trials Register are identified through
Primary outcomes search strategies based on the scope of Cochrane Airways. Details
Usage of CPAP, measured as initial acceptance, where data were of these strategies, as well as a list of handsearched conference
available, and subsequent usage as measured by: proceedings are in Appendix 1. See Appendix 2 for the search
strategy used to identify studies for this review.
1. counter output that records the cumulative time that power is
turned on to a CPAP machine (this does not provide information We also searched the following trials registries.
on actual time of day and duration of CPAP used each 24-hour
1. US National Institutes of Health Ongoing Trials Register
period);
ClinicalTrials.gov (www.clinicaltrials.gov)
2. microprocessor and monitor that measures the pressure at the
2. World Health Organization International Clinical Trials Registry
mask;
Platform (apps.who.int/trialsearch)
3. subjective participant reports of the duration of CPAP use.
Informed decisions.
3. Australian New Zealand Clinical Trials Registry Unit of analysis issues

(www.anzctr.org.au)
We entered data from cross-over studies as generic inverse variance
We searched the Cochrane Airways Trials Register and trials (GIV) outcome that were either adjusted for the within-person
registries to 15 October 2018, with no restriction on type or design or we back-calculated the standard error (SE) from exact P
language of publication. values from paired t tests, if available. For continuous data we used
MDs and their associated SEs. In the absence of either of these data,
Searching other resources we used treatment group means and standard deviations (SDs) as
if from parallel group trials.
We reviewed reference lists of all primary studies and review
articles for additional references. We contacted authors of One parallel study assessed the effects of four different auto-
identified trials to identify other published and unpublished CPAP machines compared with a device delivering fixed CPAP. We
studies. We checked for errata or retractions of included studies aggregated the data from the four treatment groups and used this
published in full text on PubMed on 8 April 2019. in our analyses (Meurice 2007).
Data collection and analysis In the forest plots we have displayed sample sizes from cross-over
studies differently to parallel group studies. To generate correct
Selection of studies
total sample sizes we have entered the total sample size to the
Two review authors independently reviewed titles, abstracts and intervention arm and 0 to the corresponding control group column.
citations identified through electronic searching to assess potential This is for display purposes only and does not affect the estimated
relevance for full review. We obtained articles deemed to be of treatment effect or the error for the study.
potential relevance for the review. Following scrutiny of full text,
two authors independently assessed studies for inclusion based Dealing with missing data
on the criteria for population, intervention, study design and Where data pertaining to mean CPAP machine usage were not
outcomes (BK and DW or TL). We measured agreement by simple available from the trial reports, we contacted study authors to
consensus. We resolved disagreement by involving a third party. determine whether data could be obtained directly. We elected to
impute SDs for one parallel group study for the primary outcome.
Data extraction and management
We generated a simple average of the SDs for other studies because
Two review authors extracted data from published and data were only reported as medians and 25th and 75th centiles.
unpublished studies independently (BK and DW or TL). We made
attempts to contact study investigators to confirm data where Assessment of heterogeneity
necessary and to provide clarification for additional information for We assessed the level of statistical variation with the I2 statistic and
the review. P value for the Chi2 test (Higgins 2003).
Assessment of risk of bias in included studies Assessment of reporting biases
Two review authors (BK and TL) assessed the risk of bias We inspected publication bias visually to check for possible
of the included studies in terms of the process of allocation asymmetry for outcomes included in the 'Summary of findings'
of participants to treatment groups (sequence generation and table with more than 10 studies.
allocation concealment), blinding in relation to objective and
subjective outcomes (judged as performance bias and detection Data synthesis
bias), subsequent impact of missing data on the analysis, selective
outcome reporting and other sources of bias. We combined data from studies where we judged the population,
interventions and definition of outcomes to be similar, using a
We judged the studies to be at low, unclear or high risk of fixed-effect model. We conducted a sensitivity analysis by using
bias and provide supporting statements from the trial reports or random-effects modelling to determine whether variation between
correspondence, as necessary. the studies affected the pooled estimate.
Measures of treatment effect Subgroup analysis and investigation of heterogeneity

We calculated mean differences (MDs) for continuous variables In the absence of any statistical heterogeneity for the outcomes
measured on identical metrics for parallel and cross-over studies. of usage and symptoms under the comparison of auto-CPAP and
We used standardised mean differences (SMDs) to combine data fixed CPAP, and the limited number of studies available for other
from studies using different scales to measure the same outcome. outcomes, we decided not to carry out any subgroup analysis (see
For one outcome we noted that variants of the Functional Differences between protocol and review for details on planned
Outcomes of Sleep Questionnaire (FOSQ) were used in two studies subgroups). We will reconsider our planned subgroups in future
(Analysis 2.4) and so we used SMDs to combine data. We report versions of the review should data become available that allows us
continuous data from meta-analyses as MDs or SMDs with 95% to assess the impact of gender or baseline AHI on the outcomes of
confidence intervals (CIs). interest.
For dichotomous outcomes, we calculated an odds ratio (OR) based Sensitivity analysis
upon the number of participants with an event versus the number We could not carry out our planned sensitivity analysis to assess the
of participants without an event. risk of bias (see Differences between protocol and review). We did
Informed decisions.
include the following sensitivity analyses for outcomes relevant to relevance for decision making and were taken for the following
the 'Summary of findings' table. latest available time points.
1. We applied random-effects modelling to assess the sensitivity 1. Average machine usage (measured as nightly average use per
of our results to the choice of statistical model. We applied this participant and as the number of participants achieving more
sensitivity analysis to outcomes where we had sufficient number than 4 hours usage per night).
of studies to use as the basis for an assumed distribution of 2. Symptoms, measured by ESS.
effects (5 or more). 3. Withdrawals.
2. For the outcome of average machine usage we decided to 4. Quality of life, measured by FOSQ.
include data from a large parallel group study which presented
5. AHI (mean number of events per hour).
data as medians and ranges instead of means and SDs (Pépin
2016). As a sensitivity analysis, we included this study by 6. Blood pressure.
assuming the medians to equate to means, and assigned 7. Adverse events (measured by tolerability of machines).
SDs based on an average of other parallel studies.
In the text of the review we have preferentially focused reporting of
Rating the certainty of evidence follow-up on these outcomes, where possible.
We rated the certainty of evidence for key outcomes as RESULTS
high, moderate, low or very low using GRADE methods, as
outlined in the GRADE Handbook (Schünemann 2013). We based Description of studies
these ratings on consideration of how risk of bias, inconsistency,
imprecision, indirectness and publication bias impact on the Results of the search
findings of outcomes most relevant to decision making. See Figure 1 for the study flow diagram for searches between 2009
and 15 October 2018. From 1566 records, 64 references describing
We have prioritised the comparison of auto-CPAP and fixed CPAP
48 potentially eligible studies were assessed for eligibility. We
over others as the basis of the conclusions of the review, but have
excluded 22 studies and included 21 studies. With the studies
included three other comparisons in the 'Summary of findings'
already included from previous searches, 64 studies met the
tables (bi-PAP, humidification and CPAP with expiratory pressure
eligibility criteria of the review. There are four ongoing studies and
relief) as they are commonly used alternatives to either fixed CPAP
one completed study is awaiting assessment.
or auto-CPAP. The outcomes we have prioritised are based on
Informed decisions.
Figure 1. Study flow diagram: review update
Informed decisions.
Figure 1. (Continued)
Top up searches in June 2019 identified 202 records, of which we Interventions

retrieved 10 for further scrutiny. Five records reported secondary
Average study duration was between 12 and 16 weeks in studies
analyses from one of the included studies (Masa 2015), and one
comparing auto-CPAP, auto-CPAPexp or bi-PAP with fixed CPAP.
referred to an excluded study (Pradeepan 2017). We also identified
Studies comparing CPAPexp or additional humidification with fixed
the published protocol for one ongoing study (NCT03428516) and
CPAP had shorter average durations (8 and 6 weeks, respectively).
conference abstract for a large completed study (NCT02749812).
We assigned two records to 'Studies awaiting classification' (see The use of standard CPAP titration protocols was common across
below). the studies. Most were conducted over one or two nights, with
the exception of Pépin 2016, where home-based pressure titration
Included studies
occurred over eight nights. Extended adaptation protocols which
Study design increased the exposure of participants to CPAP devices were
undertaken in two studies in order to establish optimal CPAP
Thirty studies have parallel groups and 33 have a cross-over
pressure and comfort prior to formal initiation of treatment (e.g.
design. In one trial (Loube 2004), the description of methods was
Senn 2003; Bloch 2018). This was used by Dolan 2008 to exclude
insufficient to determine whether the study was a parallel or cross-
participants who used CPAP for less than four hours per night
over study.
during run-in and by Ballard 2007 to identify and recruit people
Participants who averaged less than four hours per night to participate in the
randomised phase of the study.
The studies recruited 3922 participants who had been diagnosed
with sleep apnoea and had little exposure to continuous positive Automatically adjusting CPAP (auto-CPAP)
airway pressure (CPAP) before study entry. The populations had Thirty-six studies (2135 participants) compared auto-CPAP with
similar characteristics across the seven comparisons considered by fixed CPAP (Meurice 1996; Sériès 1997; Konermann 1998; d'Ortho
this review (Table 2). The proportion of male participants was high 2000; Hudgel 2000; Teschler 2000; Randerath 2001; Sériès 2001;
and ranged from 60% to 86% for the comparisons in the review. Ficker 2003; Kendrick 2002; Massie 2003; Nolan 2007; Rostig 2003;
The average age of the study populations ranged between 49 and Senn 2003; Hukins 2004; Hussain 2004; Marrone 2004; Noseda
55 and average body mass index (BMI) was between 32 kg/m2 and 2004; Resta 2004; Castronovo 2006; Jarvis 2006; Nussbaumer 2006;
35 kg/m2. Baseline sleep disruption, as measured by the Apnoea Rochford 2006; To 2008; West 2006; Fietze 2007; Meurice 2007;
Hypopnoea Index (AHI) was severe and Epworth Sleepiness Scale Patruno 2007; Galetke 2008; Damjanovic 2009; Vennelle 2010;
(ESS) scores indicated that the study populations had excessive Rohling 2011; Pépin 2016; Berry 2014; Chang 2015; Bloch 2018).
daytime sleepiness (11 to 16). One study recruited people with Treatment pressures ranged from 6.2 to 10.6 in the fixed CPAP
coexisting sleep apnoea and obesity hypoventilation syndrome groups and were lower in the auto-CPAP groups by about 1 cm H2O.
(Masa 2015).
Bilevel positive airway pressure (Bi-PAP)
The majority of studies excluded participants who had previously
used CPAP (58/64). Of the six studies actively recruiting existing Six studies (325 participants) compared bi-PAP machines
users of CPAP, Jarvis 2006 included people who were established (excluding those with automatically adjusting and expiratory
on CPAP therapy. In four studies participants were eligible if they pressure mode) with fixed CPAP (Reeves-Hoché 1995; Muir 1998;
had used CPAP but were deemed to be infrequent users (Muir 1998; Gay 2003; Gonzalez-Moro 2005; Gulati 2015; Masa 2015).
Rostig 2003; Powell 2012; Gulati 2015).
CPAP with expiratory pressure relief (CPAPexp)
Two auto-CPAP studies selected participants who required high Ten studies (658 participants) compared CPAP with expiratory
treatment pressure to correct sleep disturbance (Massie 2003; pressure relief with fixed CPAP (Loube 2004; Dolan 2008; Marshall
Noseda 2004). 2008; Nilius 2006; Gfüllner 2007; Modrak 2007; Wenzel 2007; Leidag
2008; Pépin 2009; Bakker 2010).
Most studies were conducted in Europe and North America. A
smaller number of trials were conducted in Australia (Hudgel 2000; Heated humidification plus fixed CPAP
Teschler 2000; Worsnop 2010; Hukins 2004; Jarvis 2006; Rochford
Six studies (359 participants) compared the addition of
2006), Hong Kong (To 2008; Chang 2015), New Zealand (Neill 2003;
humidification to fixed CPAP with fixed CPAP (Neill 2003; Worsnop
Marshall 2008; Bakker 2010), and Thailand (Soudorn 2016).
2010; Ruhle 2011; Ryan 2009; Heiser 2010; Soudorn 2016). There
The median study sample size is 40 (range 10 to 322). was no humidification in the control groups.
Informed decisions.
Multimodality devices we could not account for this approach in our analysis due to the
Automatically adjusting CPAP with expiratory pressure relief (auto- requirement for individual participant data.
CPAPexp)
Excluded studies
Two studies (188 participants) compared auto-CPAPexp with fixed
CPAP (Meurice 2009; Kushida 2011). We excluded 133 studies after retrieving the full text because they
did not meet the eligibility criteria of the review. Reasons for their
Bi-PAP with expiratory pressure relief (Bi-PAPexp) and auto Bi-PAPexp exclusion are detailed in the 'Characteristics of excluded studies'
table. On re-examining two previously included studies against
One study in 104 participants compared Bi-PAPexp with fixed CPAP the review eligibility criteria, we determined that one of them
(Ballard 2007). Two studies evaluated auto Bi-PAPexp with fixed was too short to be considered eligible for inclusion since they
CPAP (Blau 2012; Powell 2012). exposed participants to one week of treatment in a cross-over study
CPAPexp with wakefulness detection (Torvaldsson 2003), and the other used humidification with auto-
CPAP (Salgado 2006).
One study of 70 participants looked at CPAP with an expiratory
pressure device that responded to the detection of wakefulness and Studies awaiting classification
compared it with fixed CPAP (Bogan 2017).
One study recruiting 800 participants comparing auto-CPAP with
Outcomes fixed CPAP completed in 2015, but a conference abstract from 2018,
reports some results (NCT02749812). Following correspondence
Availabilty of outcome data for our primary outcome of machine
with the study investigators we are not anticipating full availability
usage was high. We were able to obtain data for machine usage
of the results from this study before 2020. One study of a
as either continuous or dichotomous data for 89% of studies
humidification device (Boyer 2019), and a secondary analysis of a
(57/64). Symptoms measured with ESS and sleep disturbance
CPAP compliance trial (Zamora 2019), are awaiting classification
measured with AHI were reported in 66% and 56% of studies
and we will determine their eligibility for future versions of the
respectively. Of 29 studies providing data on treatment pressure
review.
(45%), 24 compared auto-CPAP with fixed CPAP.
Ongoing studies
Quality of life was reported in 23 studies (36%). Two instruments
validated in sleep apnoea research were used in 11 studies (Sleep Six studies are listed as ongoing. We have not been able to
Apnoea Quality of Life Index (SAQLI) and Functional Outcomes of determine whether interim results from two studies presented
Sleep Questionnaire (FOSQ)) either in combination with the Short- as conference abstracts have been superseded by reports of
Form 36 (SF-36) or on their own. For the remaining studies, only the completed studies (Morton 2001; Ventateswaren 2003). One
SF-36 was used. published protocol pertains to a study in rescue workers who
developed OSA subsequent to the collapse of the World Trade
There was considerable variation in the methods used to measure
Centre in New York, USA in 2001 (NCT01753999). Two small studies
tolerability or adverse events in 23 studies (36%). Studies used diary
evaluate auto-CPAP (ACTRN12618000379213p; NCT01753999), and
records and interviews to capture effects as both dichotomous data
one is assessing a device that delivers pressure to the upper airway
(did or did not experience the event) or scales to rate problems with
through one nostril at a time (ACTRN12617001090303).
mask leak, pressure tolerance, dry mouth and nasal symptoms.
Variation in how this was done prevented us from combining data Risk of bias in included studies
in a meta-analysis for many comparisons of interest. A number
of cross-over studies reported unadjusted dichotomous data and An overview of the study level judgements is provided in Figure 2.
Informed decisions.
Figure 2. Methodological quality summary: review authors' judgements about each methodological quality item
for each included study.
Informed decisions.
Informed decisions.
Allocation bias domain only (Marrone 2004). For the remaining studies, one or
both domains were at unclear risk of bias.
We considered 21 studies to be at low risk for both selection bias
domains and one study had a high risk of bias for both domains
(Hudgel 2000). One study was at high risk of bias in one selection
Informed decisions.
Blinding Other potential sources of bias

We judged that the open-label or single-blind design used in many We could not find any reason to consider the studies at high risk of
of the studies would likely have had a greater impact on usage other sources of bias. We could not reliably assess this domain in 11
outcomes, withdrawal and subjectively reported outcomes than studies, only available as conference abstracts, and judged them to
on AHI, treatment pressure and blood pressure (see Figure 2). be at unclear risk of bias.
Measures to reduce the risk of bias arising from study personnel
and participants becoming aware of treatment group assignment Effects of interventions
resulted in low risk of bias for subjective outcomes in 21 studies,
See: Summary of findings for the main comparison Auto-CPAP
a high risk of bias in 29 studies and unclear for the remainder. We
compared to fixed CPAP for sleep apnoea in adults; Summary
judged objective outcomes to be at low risk of performance bias in
of findings 2 Bi-PAP compared to fixed CPAP for sleep apnoea
53 studies. Our 'Risk of bias' judgements for outcome assessment
in adults; Summary of findings 3 CPAP with expiratory pressure
followed closely those we made for performance bias, given that
relief compared to fixed CPAP for adults with obstructive sleep
participants would have been rating symptoms and quality of life.
apnoea; Summary of findings 4 Heated humidification + fixed
Incomplete outcome data CPAP compared to fixed CPAP alone in adults with obstructive sleep
apnoea
We judged a total of 24 studies to be at a low risk of attrition bias
across the outcomes of interest (see Figure 2). This was primarily Automatically adjusting continuous positive airway pressure
where loss to follow-up was low enough to not affect the outcomes (auto-CPAP) versus fixed continuous positive airway pressure
of interest (very limited and balanced attrition or where all study (fixed CPAP)
participants completed). We noted that risk of attrition affected
Primary outcomes
cross-over and parallel group studies in different ways. A number
of cross-over participants who withdrew and did not cross over Machine usage
to the second arm of the trial were excluded from the analysis. Auto-CPAP probably increases average nightly usage by about
Withdrawals for a number of long-term parallel group studies 13 minutes per person compared with fixed CPAP at a median
meant that loss to follow-up affected the long-term outcome follow-up of six weeks (mean difference (MD) 0.21 hours/night, 95%
measurements. Twenty-two studies had a high risk of bias and we confidence interval (CI) 0.11 to 0.31; 31 studies, 1452 participants;
judged the remainder as unclear. moderate-certainty evidence; Analysis 1.1, Figure 3). Average
machine usage in the fixed CPAP arms was about five hours per
Selective reporting
person per night. Fixed-effect and random-effects meta-analysis
Where trial registry records have been available for a study we have results were identical. Data from one large parallel group trial
been able to cross-check prespecified outcomes against what was could not be used in the primary analysis because only medians
reported. We found evidence of selective outcome reporting for and interquartile ranges were available (Pépin 2016, N = 322). We
'Summary of findings' table outcomes in seven studies (Gay 2003; decided to incorporate this study as a sensitivity analysis because
Fietze 2007; Patruno 2007; Meurice 2009; Heiser 2010; Vennelle the sample size was bigger than any others in the analysis and the
2010; Powell 2012). The impact of this selective reporting on the direction of effect was potentially discordant. Including this study
overall results was limited. with imputed standard deviations (SDs) attenuated slightly the size
of effect (MD 0.19 hours/night, 95% CI 0.10 to 0.29; 32 studies, 1774
participants; Analysis 1.2).
Informed decisions.
Figure 3. Forest plot of comparison: 1 Auto-CPAP versus fixed CPAP, outcome: 1.1 Machine usage (hours/night).
The number of people who use their machines for four hours or Additional measures of usage indicate the increase in average
more per night may be slightly higher with auto-CPAP, although the effect could be driven by higher use on specific nights rather than
CIs include both substantially fewer and substantially more people incrementally greater use on all nights with auto-CPAP (Analysis
with auto-CPAP (odds ratio (OR) 1.16, 95% CI 0.75 to 1.81; 2 studies, 1.4; Analysis 1.5; Analysis 1.6).
346 participants; low-certainty evidence; Analysis 1.3).
Informed decisions.
Secondary outcomes (I2 = 92%). Both fixed- and random-effects models indicate lower
Symptom scores average pressure with auto-CPAP (fixed-effect MD -1.01 cm H2O,
95% CI -1.17 to -0.84, random-effects MD -1.49 cm H2O, 95% CI
Auto-CPAP probably reduces the Epworth Sleepiness Scale (ESS)
-2.12 to -0.85; 24 studies, 1171 participants; Analysis 1.14). Despite
score by a small degree compared with fixed CPAP at three to
the different mechanisms used to deliver mask pressure between
16 weeks (MD -0.44 units, 95% CI -0.72 to -0.16; 25 studies, 1285
the devices, in some studies the delivered treatment pressure was
participants; moderate-certainty evidence; Analysis 1.7). Average
equivalent between auto-CPAP and fixed CPAP, whilst in others
ESS scores following fixed CPAP treatment ranged from 4.1 to
the mean treatment pressure in auto-CPAP was between 3 cm
8.6. There was no statistical heterogeneity and changing statistical
H2O and 5 cm H2O lower. Differences in algorithms used by the
model had no impact on the pooled result.
different machines used to alter pressure (e.g. forced oscillation),
Withdrawals variation in peak treatment pressure within study populations and
the selection of participants on the basis of high treatment pressure
The likelihood of withdrawal is probably similar between the two required in others (e.g. Massie 2003; Noseda 2004), could contribute
devices at six weeks (auto-CPAP: 10% versus fixed CPAP: 11%), to the conflicting results.
although the CI includes a slightly higher risk of withdrawal with
both devices (OR 0.90, 95% CI 0.64 to 1.27; 13 studies, 1275 Blood pressure
participants; moderate-certainty evidence; Analysis 1.8).
Systolic blood pressure
Quality of life scores Our analysis could not exclude a potentially small decrease or
Functional Outcomes of Sleep Questionnaire (FOSQ) increase in systolic blood pressure with auto-CPAP at 12 to 16 weeks
(MD 1.87 mmHg, 95% CI -1.08 to 4.82; 2 studies, 353 participants;
Quality of life measured as FOSQ may be similar between auto- moderate-certainty evidence; Analysis 1.15). We were unable to
CPAP and fixed CPAP (MD 0.12 units, 95% CI -0.21 to 0.46; 3 studies, extract data from Nolan 2007 and West 2006. Neither study reported
352 participants; low-certainty evidence; Analysis 1.9). There was significant differences between auto-CPAP and fixed CPAP.
wide variation in the follow-up for these studies (4 to 104 weeks).
Diastolic blood pressure
Sleep Apnoea Quality of Life Index (SAQLI)
Diastolic blood pressure was higher at the end of the study
Two trials assessing for changes in SAQLI found no significant period with auto-CPAP than with fixed CPAP at 12 to 16 weeks
difference in the effects of auto-CPAP and fixed CPAP (MD -0.14 (2.92 mmHg; 95% CI 1.06 to 4.77; 2 studies; 353 participants;
units, 95% CI -0.54 to 0.27; Analysis 1.10). low-certainty-evidence; Analysis 1.16). Nolan 2007 reported no
Short-Form 36 (SF-36) significant difference between auto-CPAP and fixed CPAP but did
not provide numerical values.
Eight studies provided data on quality of life measured with the
SF-36 (Analysis 1.11). The number of studies contributing data to Additional measures of blood pressure did not indicate any
each domain varied from two (role physical, bodily pain, general meaningful differences in blood pressure, namely 24-hour mean,
health and social functioning) to six (vitality). Effect sizes ranged systolic and diastolic blood pressure: Analysis 1.17; Analysis 1.18
from a reduction of 6 points with auto-CPAP on physical health and Analysis 1.19); diurnal mean, systolic and diastolic blood
domain to a 6-point increase with auto-CPAP on general health pressure (Analysis 1.20; Analysis 1.21; Analysis 1.22), and nocturnal
domain. Hukins 2004 reported no significant differences between mean, systolic and diastolic blood pressure (Analysis 1.23; Analysis
treatment groups. 1.24; Analysis 1.25).
Sleep disruption Adverse events

Apnoea Hypopnoea Index (AHI) Data on tolerability outcomes were measured and reported
There is a slightly higher AHI with auto-CPAP compared with fixed inconsistently across the studies. We have presented a narrative
CPAP at six weeks (MD 0.48 events/hour, 95% CI 0.16 to 0.80; 26 summary of the data from individual studies for each main
studies, 1256 participants; high-certainty evidence; Analysis 1.12). symptom associated with machine usage. Data from one study
There was a high level of statistical heterogeneity that we could could be presented in Analysis 1.26. For the remainder, data were
presented graphically or we could not adjust data adequately for
attribute to the inclusion of a single study (I2 = 51%; Patruno 2007).
the cross-over design.
Neither excluding Patruno 2007 nor applying a random-effects
model substantially altered the direction, precision or size of the Due to the risk of bias across the studies, variation in the methods
effect. used to measure this outcome and the use of unvalidated scales
for some of the studies, we rated the certainty of evidence for
Arousals
tolerability outcomes to be very low (see Summary of findings for
There is insufficient evidence to determine the comparative effect the main comparison). We have been unable to obtain data from
of the devices on arousals (MD -0.66 events/hr, 95% CI -2.90 to 1.58; one study of 181 people that measured CPAP side effects using
4 studies, 136 participant; Analysis 1.13). the Edinburgh checklist but did not report these findings (Vennelle
2010). Follow-up ranged from 4 to 36 weeks.
Treatment pressure
There was a high degree of statistical variation in the size and

direction of differences in treatment pressures across the studies
Informed decisions.
Nasal blockage Mask leak
Four participants in Sériès 1997 suffered nasal blockage (2 from Bloch 2018 reported a slightly higher proportion of participants
auto-CPAP1 group, one from auto-CPAP2, and one from fixed reporting mask leak in the auto-CPAP group (37% versus
CPAP), which resolved with the use of a heated humidifier. Bloch 34%); Nolan 2007 presented data that indicated slightly fewer
2018 presented data from the per protocol population, reporting participants experiencing leak with auto-CPAP (just over 20%
similar rates of nasal blockage at 2 years (31% in both groups, versus just under 25% based on visual inspection).
N = 144). Nolan 2007 presented bar charts of those experiencing
blocked or runny nose during both arms of treatment (just over 40% Teschler 2000 reported no significant difference in mask leak
in those treated with auto-CPAP and just over 30% in those with between fixed CPAP (13% mask on time with leak of 0.4 L/second)
fixed CPAP based on visual inspection, N = 26). and auto-CPAP (10% mask on time with leak of 0.4 L/second). Four
studies reported slightly fewer leaks as either number of leaks per
Nussbaumer 2006 reported similar scores between treatment arms person, leakage time or pressure leaked per second with auto-
by participants who rated symptoms on a visual analogue scale CPAP compared with CPAP (Hukins 2004; West 2006; Galetke 2008;
(VAS) (N = 38). Damjanovic 2009). Nussbaumer 2006 found that mask leaks were
perceived to be less problematic on auto-CPAP than on fixed CPAP.
Dry mouth
Participant preference
Bloch 2018 reported lower rates of dry mouth in the auto-CPAP
group than with fixed CPAP (46% versus 56%), whereas in Nolan The results from the studies indicate wide variation in terms of
2007 the direction of effect was the reverse (just under 45% versus preferences expressed by users of CPAP between the different
35% with fixed CPAP, based on visual inspection). machine types. In eight of the 14 studies reporting this outcome,
on average people preferred auto-CPAP over either fixed CPAP, or
Paticipant-reported symptoms were slightly lower in the auto-CPAP neither treatment. However, in six studies, people preferred fixed
arm in Nussbaumer 2006. CPAP (Senn 2003; Hussain 2004; Jarvis 2006; To 2008; Vennelle
2010; Rohling 2011). In Senn 2003 the majority of participants
Tolerance of treatment pressure
(21/29) preferred neither treatment: but in Hussain 2004 (6/10) and
Bloch 2018 reported lower rates of excessive mask pressure with To 2008 (30/41) the majority preferred treatment with fixed CPAP.
auto-CPAP than with fixed CPAP (46% versus 51%), as did Nolan In Jarvis 2006 (11/20), Vennelle 2010 (112/181) and Rohling 2011
2007 (18% versus 21%). (20/33), more participants expressed preference for fixed CPAP or
no preference than preference for auto-CPAP. We were unable to
Massie 2003 reported a significant difference between auto-CPAP find a satisfactory explanation for this apparent discrepancy in
and fixed CPAP in favour of the automatic pressure mode on feeling terms of study design and technology of active interventions.
discomfort from pressure and experiencing less trouble getting to
sleep (all values P < 0.006). Randerath 2001 reported no significant Bilevel positive airway pressure (Bi-PAP) versus fixed CPAP
differences between the two groups who were treated with both
Primary outcomes
auto and fixed CPAP (no numerical values presented). d'Ortho
2000 reported little difference on an unvalidated questionnaire Machine usage
measuring tolerance of treatment pressure between auto-CPAP
There is insufficient evidence to determine the effect of Bi-PAP on
and fixed CPAP (N = 25). In Nussbaumer 2006 participant-rated
average machine usage (0.14 hours/night, 95% CI -0.17 to 0.45;
tolerance of treatment pressure was better in the auto-CPAP arm
4 studies; 268 participants; low-certainty evidence; Analysis 2.1,
than during fixed CPAP treatment.
Figure 4). Follow-up ranged from 4 to 52 weeks.
Informed decisions.
Figure 4. Forest plot of comparison: 2 Bi-PAP versus fixed CPAP, outcome: 2.1 Machine usage (hours/night).
Secondary outcomes events/hour, 95% CI -6.92 to 9.63; 2 studies; 179 participants;

Analysis 2.7).
Symptom scores
Epworth sleepiness scores (ESS) reduced from baseline with both Treatment pressure
devices in four studies with follow-up from four to 12 weeks, Gulati 2015 provided a measurement of the two levels of pressure
but there is insufficient evidence available to determine the for inhalation and exhalation. Against a control mean of 11.45
comparative effects of Bi-PAP and fixed CPAP on symptoms (-0.49 cmH2O the average pressure at inhalation was 13 cmH2O and at
ESS units, 95% CI -1.46 to 0.48; 226 participants; low-certainty exhalation was 4.1 cmH2O.
evidence; Analysis 2.2).
Withdrawals
Muir 1998 reported that both CPAP and bi-PAP were preferred by
There is insufficient evidence to determine whether withdrawal is
40% of participants, while 20% did not express a preference.
more likely with Bi-PAP (OR 0.55, 95% CI 0.26 to 1.17; 3 studies;
261 participants; low-certainty evidence; Analysis 2.3). Follow-up Adverse events
ranged from four to 52 weeks.
Follow-up across the five studies providing information for these
Quality of life scores outcomes ranged from four to 52 weeks.
Functional Outcomes of Sleep Questionnaire (FOSQ)
Reeves-Hoché 1995 reported five withdrawals due to either mask
There is insufficient evidence from one small eight-week trial to discomfort (n = 2) or therapy intolerance (n = 3). All were from the
determine the effects of Bi-PAP on FOSQ (low-certainty evidence, CPAP group. No withdrawals due to mask discomfort or therapy
Analysis 2.4). intolerance occurred from the bi-PAP group. Twenty participants
complained of nasal dryness (no distribution between the 2 groups
Sleep Apnoea Quality of Life Index (SAQLI) reported). Three participants complained of rhinorrhoea and 15
There is insufficient evidence to determine the effects of Bi-PAP on participants complained of nasal bridge pressure (no distribution
SAQLI from one study (Analysis 2.5). reported between the 2 groups). Masa 2015 reported similar rates of
dry mouth and mask intolerance in the treatment groups (Analysis
Short-Form 36 (SF-36) 2.9).
There is insufficient evidence to determine the effects of Bi-PAP on Gay 2003 reported that telephone contact did not identify any
SF-36 sub domains of physical and mental health from one study complications that necessitated further interventions. Muir 1998
(see Analysis 2.6). did not report data in terms of specific adverse events; no difference
Sleep disruption
in the rate of adverse events was reported. Gulati 2015 used a global
treatment comfort score on a 0-100 VAS but there was insufficient
Apnoea Hypopnoea Index (AHI) evidence to determine the effect (Bi-PAP: 69 versus fixed CPAP: 60,
There is insufficient evidence from two studies at four to eight P = 0.16).
weeks duration to determine the effect of Bi-PAP on AHI (1.36
Informed decisions.
CPAP with expiratory pressure relief (CPAPexp) versus fixed follow-up of two to 24 weeks (0.14 hours/night, 95% CI -0.07 to
CPAP 0.35; 9 studies, 609 participants; low-certainty evidence; Analysis
3.1, Figure 5).
Primary outcomes
Machine usage
CPAPexp may be used more than fixed CPAP although the CI

includes little or no difference in usage in studies, with a range of
Figure 5. Forest plot of comparison: 3 CPAP with expiratory pressure relief versus fixed CPAP, outcome: 3.1 Machine
usage (hours/night).
Secondary outcomes Short-Form 36 (SF-36)
Symptom scores Two studies reported SF-36, but only one provided data suitable
for analysis. There was insufficient evidence to determine the
The effects of CPAPexp and fixed CPAP on symptom scores are
comparative effect of these treatment modes on the different
probably similar in studies with a range of follow-up of two to
domains of the SF-36 (Analysis 3.5).
24 weeks (0.17 ESS units, 95% CI -0.26 to 0.60; 6 studies, 515
participants; moderate-certainty evidence; Analysis 3.2). Sleep disruption
Withdrawals Apnoea Hypopnoea Index (AHI)
There is insufficient evidence to determine the effects of CPAPexp There is little or no difference in AHI at the end of the study period
and fixed CPAP on withdrawal at 12 weeks (OR 0.86, 95% CI 0.48 ranging from four to 24 weeks (0.24 events/hr, 95% CI -0.49 to 0.96;
to 1.55; 2 studies, 298 participants; low-certainty evidence; Analysis 5 studies, 342 participants; high-certainty evidence; Analysis 3.6).
3.3).
Treatment pressure
Quality of life
There is probably little or no difference in treatment pressure
Functional Outcomes of Sleep Questionnaire (FOSQ) between the two groups (-0.05cmH2O, 95% CI -0.63 to 0.52 cmH2O;
There may be little difference in FOSQ between treatment modes 2 studies, 241 participants; moderate-certainty evidence; Analysis
based on evidence from one 12-week study in 74 participants (-0.40 3.7).
FOSQ units, 95% CI -1.15 to 0.35; low-certainty evidence; Analysis Adverse events
3.4).
No specific measures of nasal or oral symptoms were carried out in
the trials which ranged in follow-up from four to 24 weeks.
Informed decisions.
Four studies assessed treatment comfort scores. One parallel 19.5) and 59.8 (SD 20.8) L/min, P = 0.30), or in average leak (43.7
group trial reported data from questionnaires which indicated that (SD 14.8) and 47.6 (SD 16.8) events/h, respectively; P = 0.31). Leidag
CPAPexp was regarded as a more tolerable treatment than fixed 2008 reported that leakage in fixed CPAP mode was 27.5 (SD 11.5)
CPAP by users, and led to greater satisfaction with treatment (Dolan L/min and in CPAPexp was 28.0 (SD 10) L/min.
2008; Analysis 3.8; Analysis 3.9; Analysis 3.10). Gfüllner 2007 did not
find a significant difference between the two treatments (measured Particpant preference
as treatment comfort scores (CPAPexp: 6.9 versus fixed CPAP: 6.0). Leidag 2008 reported that the treatment modes were equally likely
Nilius 2006 reported that after seven weeks of treatment, average to be preferred by the study participants.
tolerability scores were 15.5 in the CPAPexp group and 16.5 in the
fixed CPAP group. An analysis of the individual questions after seven Heated humidification + fixed CPAP versus fixed CPAP alone
weeks revealed no statistically significant difference between the
Primary outcomes
groups for any item. Pépin 2009 reported no statistically significant
differences in assessments of side effects and comfort between the Machine usage
treatment modes.
Humidification may increase use of fixed CPAP by 0.37 hours per
Mask leak person per night, with a range of follow-up of three to 12 weeks
(95% CI 0.10 to 0.64; 6 studies, 277 participants; low-certainty
Bakker 2010 reported no significant difference between CPAPexp evidence; Analysis 4.1; Figure 6).
and fixed CPAP in 90th percentile leak (54.8 (standard deviation (SD)
Figure 6. Forest plot of comparison: 4 Heated humidification + fixed pressure CPAP versus fixed pressure CPAP
alone, outcome: 4.1 Machine usage (hours/night).
Secondary outcomes Quality of life scores
Symptom scores Short-Form 36 (SF-36)
There may be little difference in ESS between those receiving The effect of humidification on SF-36 General Health Perception
humidification and those who did not based on four studies with scores was uncertain (0.11, 95% CI -6.97 to 7.18; 2 studies; 124
a range of follow-up of three to 12 weeks (MD -0.34, 95% CI participants, Analysis 4.5).
-0.93 to 0.26; 184 participants; low-certainty evidence; Analysis
Sleep disruption
4.2). Salgado 2006 reported no significant difference between
treatments, but did not provide numerical values. Apnoea Hypopnoea Index (AHI)
AHI was measured in one small study of four weeks duration (N =

44). The effect of humidification on AHI was uncertain (0.30 events/
hr higher (0.95 lower to 1.55 higher; Analysis 4.4; low-certainty
evidence).
Informed decisions.
Adverse events DISCUSSION

Results for different unvalidated measures of nasal symptoms were
reported by two studies as dichotomous data (Neill 2003; Ryan
Summary of main results
2009), and by two studies as continuous data (Heiser 2010; Worsnop This updated systematic review includes 64 studies assessing
2010). There was insufficient evidence to reliably determine the the effect of pressure modification and humidification on clinical
effect of additional humidification on symptoms of dry, runny, outcomes in adults with obstructive sleep apnoea (OSA). The
blocked or bleeding nose measured as either events (Analysis addition of six studies to our main comparison has strengthened
4.6), or when rated as symptom scores (Analysis 4.7). The average the conclusions from the previous version of this review regarding
duration was around four weeks. the comparative effects of automatically adjusting continuous
positive airway pressure (auto-CPAP) and CPAP with fixed pressure
setting (fixed CPAP).
Neill 2003 showed no significant difference in the number of
participants expressing a preference for humidification over no Auto-CPAP probably increases machine usage by about 13 minutes
humidification. per person per night when compared to fixed CPAP over
three months (moderate-certainty evidence). It probably reduces
Multimodality devices versus fixed CPAP symptoms by a small amount (less than 0.5 points on the Epworth
Sleepiness Scale (ESS)) over fixed CPAP (moderate-certainty
Automatically adjusting CPAP with expiratory pressure relief evidence). Fixed CPAP was slightly more effective at reducing the
(auto-CPAPexp) versus fixed CPAP Apnoea Hypopnoea Index (AHI) (high-certainty evidence) and it
Kushida 2011 and Meurice 2009 compared auto C-Flex with fixed may lower diastolic blood pressure by 3 mmHg compared with
CPAP. There was no evidence of a difference in compliance between auto-CPAP (low-certainty evidence). Variation in the approach
the two devices (0.03 hours, 95% CI -0.66 to 0.67; 2 studies, 113 to measuring adverse events from the devices meant that we
participants). Results for the remaining outcomes did not provide could not determine whether the lower nightly average delivered
sufficient evidence to determine the effects on symptoms, quality treatment pressure of between 1 cmH2O and 3 cmH2O with auto-
of life or blood pressure (Analysis 5.2; Analysis 5.3; Analysis 5.4; CPAP had any associated impact on participant-rated tolerability
Analysis 5.5; Analysis 5.6; Analysis 5.7; Analysis 5.8). outcomes.
Bi-PAP with expiratory pressure relief (Bi-PAPexp) versus fixed There is low-certainty evidence that humidification increases
CPAP average nightly machine usage, but more studies are needed to
confirm this effect and to evaluate clinical outcomes, including
Ballard 2007 compared Bi-PAPexp (Bi-Flex) to fixed CPAP in 104
symptoms and quality of life. The remaining studies reflect small,
participants who remained poorly compliant with fixed CPAP after
developing evidence bases for novel modes of pressure delivery,
standard interventions such as mask optimisation, humidification
such as CPAP with expiratory pressure relief (CPAPexp) and
and sleep apnoea education; they reported increased machine use
automatically adjusting bilevel positive airway pressure (auto bi-
with Bi-Flex, measured as an average of hours per night (3.7 hours
PAP).
versus 2.9 hours; Analysis 6.1), and as the number of participants
who used the machines for more than four hours per night (Analysis Overall completeness and applicability of evidence
6.2). There was insufficient evidence to determine the effect on
quality of life and no measurement of symptoms, withdrawals, AHI, The populations recruited to the studies were predominantly
blood pressure or adverse events. male with a recent diagnosis of OSA and little previous exposure
to CPAP. At baseline, the study populations had high body mass
Automatically adjusting (auto bi-PAP) versus fixed CPAP index (BMI) and AHI scores, and symptom scores indicated that
Powell 2012 and Blau 2012 compared auto bi-PAP with fixed CPAP they had excessive daytime sleepiness. Most of the studies to
in 83 participants with poor initial experience of CPAP. There was date have compared auto-CPAP with fixed CPAP and measured
insufficient evidence to determine the effects on machine usage machine usage, symptoms and AHI, with most studies completing
(MD 0.00 hours/night, 95% CI -0.70 to 0.70; Analysis 7.1), number of measurement of outcomes at short term (i.e. 12 weeks or less).
participants who used machines for more than four hours (Analysis There is less information on quality of life, reflecting the relatively
7.2), symptoms (Analysis 7.3), withdrawals (Analysis 7.4), quality of recent development and use of validated specific quality of life
life (Analysis 7.5), and AHI (Analysis 7.6). scales in OSA trials. The fragmentary nature of the evidence for
tolerability outcomes, across all of the comparisons in the review,
CPAP with expiratory pressure relief (CPAPexp) with wakefulness reflects different approaches to capturing information on these
detection versus fixed CPAP outcomes by the study investigators.
There was insufficient evidence from one study of CPAPexp Auto-CPAP versus fixed CPAP
designed to alter pressure as it detects wakefulness to determine
the effects on machine usage, AHI, symptoms, quality of life and The lack of associated clinically meaningful differences in
mask leak (Bogan 2017). symptoms, quality of life and AHI suggests that the average increase
in machine usage of 13 minutes per night with auto-CPAP is too
small to be clinically meaningful. Our results indicate that both
machine types reduce symptoms, but that the difference between
them is unlikely to be clinically important. At the end of the
treatment period ESS fell in both groups to between 4 and 8 from
baseline values of about 13 (Summary of findings for the main
Informed decisions.
comparison). The end of treatment difference of 0.5 units is smaller ischaemic attack by 15%. Similarly, Law 2009 reported that a drop
than the minimal clinically important difference of between 2 and of 5 mmHg in diastolic blood pressure would reduce risk of coronary
3 (Patel 2018). There is evidence of a ceiling effect in symptoms disease by 25% and risk of stroke by 36%.
once CPAP usage exceeds four hours per night (Weaver 2007). Many
participants in both groups used machines for more than four On balance, we remain cautious about the effect on diastolic
hours per night, reducing the scope for any meaningful differences blood pressure. Diastolic blood pressure was one of 11 parameters
in symptoms (Appendix 3). It should also be acknowledged that of blood pressure that were analysed in this review; thus we
average study duration was between 12 and 16 weeks; therefore cannot exclude multiplicity as a cause of this finding. Other
one should be wary of using these short-term results to predict parameters of blood pressure from larger sample sizes did not
long-term outcomes. show similar effects (clinic systolic or 24-hour, diurnal or nocturnal
systolic, diastolic or mean blood pressure). Baguet 2013 argue
Few studies have used OSA-specific quality of life instruments. The that 24-hour ambulatory blood pressure monitoring rather than
mean differences in Functional Outcomes of Sleep Questionnaire office-measured blood pressure is necessary to detect masked
(FOSQ) and Sleep Apnoea Quality of Life Index (SAQLI) scores hypertension (i.e. normal office BP but elevated ambulatory
between auto-CPAP and fixed CPAP treatment arms did not exceed measurements) which is present in 30% of adults with OSA and is
minimally important differences that have been reported for these a known risk factor for cardiovascular disease (Bobrie 2008; Angeli
questionnaires, i.e. 1 unit (Billings 2014). From generic Short-Form 2010). Our confidence in this effect was low due to very serious
36 (SF-36) questionnaire scores, auto-CPAP participants reported a inconsistency; Patruno 2007 reported that fixed CPAP participants
bodily pain score that was 4.2 units higher, a general health score had a diastolic blood pressure that was almost 7 mmHg lower than
that was 2.5 units higher and a role physical score that was 3.7 auto-CPAP participants; Pépin 2016 reported this difference to be
units lower than fixed CPAP participants. Whilst such differences less than 2 mmHg. Furthermore Pépin 2016 reported that the mean
have been reported to be clinically meaningful in other conditions change in diastolic blood pressure from baseline did not differ
(Swigris 2010; Ward 2014), it is unclear whether these results between fixed CPAP and auto-CPAP. Finally, in the nine ambulatory
would translate into meaningful differences in OSA participants. measurements of blood pressure made by Pépin 2016 and Bloch
The confidence intervals (CIs) around these effects are wide, and 2018, there were no differences between fixed CPAP and auto-CPAP
there are no studies specifying the minimally important difference in any blood pressure parameter, either at the end of the study
in the SF-36 questionnaire for adults with OSA. period or in the mean change from baseline.
Inconsistent approaches to measuring tolerability across the There is weak consensus among investigators as to the optimal
studies made it difficult to improve our understanding of harms measurement of blood pressure in adults with OSA. Future research
from both device types. Although 11 studies reported on four should identify which parameter of blood pressure best correlates
main tolerability outcomes (nasal blockage, dry mouth, intolerance with cardiovascular morbidity and mortality in adults with OSA.
of treatment pressure and mask leak), combining data in a The effect on diastolic blood pressure requires further clarification
single analysis for any one outcome was not possible for our given the risks associated with hypertension in OSA and recent
main comparison. Some studies measured tolerability outcomes evidence suggesting that auto-CPAP and fixed CPAP produce
dichotomously (Sériès 1997; Bloch 2018); others used a visual different biological effects (Marrone 2018).
analogue scale (VAS) to enable participants to assess the impact
of various adverse events (d'Ortho 2000; Massie 2003; Nussbaumer Effects in previous users of CPAP
2006). A standardised approach to measuring CPAP tolerability has People who have previously used CPAP prior to study entry are
yet to become universally adopted (Boström 2010b). Building on under-represented in studies included in our review. Although we
existing efforts to arrive at an agreed approach to the definition have not been able to carry out formal subgroup analysis, the
and measurement of tolerability outcomes in CPAP research would results of the studies that have recruited from this population
help to improve our understanding of the relationship between do not provide evidence of substantially different results in terms
tolerability, continued machine usage and symptomatic changes. of both usage or functional outcomes. Rostig 2003 showed that
auto-CPAP improved compliance by about 30 minutes in a cross-
At the end of the study period, participants on fixed CPAP had
over trial of 30 participants who were on long-term CPAP but
a diastolic blood pressure that was almost 3 mmHg lower than
whose hours of use were less than four hours per night. Ballard
participants on auto-CPAP. It is certainly biologically plausible
2007 showed that Bi-Flex improves machine usage by 36 minutes
that fixed CPAP is more effective than auto-CPAP in lowering
compared to fixed CPAP in participants with CPAP compliance
diastolic blood pressure. Diastolic hypertension is thought to arise
of less than four hours per night, despite undergoing a CPAP
from peripheral vasoconstriction, which itself is a consequence
optimisation intervention; however, there were no differences in
of sympathetic activation (Pépin 2014). Auto-CPAP has been
FOSQ scores between the two groups. Gulati 2015 found that both
associated with more sympathetic activation than fixed CPAP
Bi-PAP or an alternative fixed CPAP device improved compliance
(Patruno 2014), which may lead to relative diastolic hypertension
by over two hours in participants with symptoms of pressure
in people who are using auto-CPAP. Furthermore, we observed
intolerance and fixed CPAP use of less than four hours per night;
a slightly higher AHI in auto-CPAP participants, which could be
however, there were no significant differences between Bi-PAP
associated with increased sympathetic activation.
and alternative CPAP in terms of hours of use, ESS, Oxford Sleep
Given the high rates of compliance, the reduction in diastolic blood Resistance (OSLER) sleep latency or SAQLI score. Powell 2012
pressure achieved by fixed CPAP in relation to auto-CPAP may showed that auto bi-PAP did not improve CPAP compliance, ESS or
have implications for cardiovascular outcomes. Cook 1995 reported FOSQ score in participants with a suboptimal CPAP titration.
that a 2 mmHg drop in diastolic blood pressure could reduce risk
of coronary heart disease by 6% and risk of stroke and transient
Informed decisions.
Certainty of the evidence Our decision to use a threshold of four hours as a measure
of adequate machine usage could be contested. We chose
The certainty of evidence varied across the different outcomes for
this threshold as research indicates that resolution of daytime
the four comparisons we assessed. Our downgrading decisions
sleepiness requires a minimum of four hours of CPAP use per
were based on concerns about risk of bias, imprecision or
night (Weaver 2007). The optimal 'dose' of CPAP selected will
inconsistency, although their impact varied across the different
depend on whether the intention of treatment is to modify blood
outcomes.
pressure, subjective or objective sleepiness, functional status,
In the comparison of auto-CPAP and fixed CPAP we downgraded as well as what individuals require (Masa 2014; Bakker 2019).
the certainty of evidence for average machine usage to moderate Whilst it is likely that optimal dosing does indeed vary between
due to risk of bias, and machine usage for four hours or more individuals and by therapeutic aim, we have retained the view that
per night to low for risk of bias and imprecision (Summary of a consistently applied threshold across a population that reflects
findings for the main comparison). For the remaining comparisons, symptomatic change reflects an important goal of treatment for
we downgraded average machine usage to low for risk of bias and adults with OSA. In the absence of more refined ways of identifying
imprecision. We rated effects on symptoms as moderate certainty changes in individuals, we think that continuous and dichotomous
for auto-CPAP and CPAPexp due to risk of bias (Summary of findings measurements of machine usage provide complementary insights
for the main comparison; Summary of findings 3), and as low to inform treatment decisions.
for Bi-PAP and humidification due to risk of bias and imprecision
(Summary of findings 2; Summary of findings 4).
Agreements and disagreements with other studies or
reviews
Across all the comparisons, the certainty of evidence for quality
Two other meta-analyses have compared auto and fixed CPAP (Ip
of life outcomes is low and this reflects the relatively recent use
2012; Xu 2012), and a third network meta-analysis compared auto-
of validated scales in sleep apnoea trials. The very low-certainty
CPAP, fixed CPAP and oral appliances (Liu 2017). Ip 2012 and Xu
evidence for tolerability outcomes for all the comparisons is due
2012 report very similar effect sizes to our own, with auto-CPAP
to variation in how this outcome has been measured across the
resulting in an additional 11 minutes and 14 minutes of nightly
studies. We rated the certainty of evidence for AHI as high for the
usage, respectively. Ip 2012 also found a small decrease in ESS with
comparisons of auto-CPAP and CPAPexp with fixed CPAP (Summary
auto-CPAP and Xu 2012 reported statistically significant decreases
of findings for the main comparison; Summary of findings 3).
in treatment pressure with auto-CPAP.
We would expect the impact of long-term attrition to be smaller
on these outcomes, as the results are consistent with immediate Ip 2012 estimated that fixed CPAP lowered diastolic blood pressure
changes to sleep disturbance which arise from using positive by 8 mmHg (95% CI 4 to 11 mmHg, P < 0.001) more than auto-CPAP.
airway pressure, irrespective of the device. In the comparison of This 8 mmHg difference is markedly greater than that observed
auto-CPAP and fixed CPAP, we regard attrition as a less important in our study (3 mmHg); the more modest effect in our study is
source of uncertainty on the size of effect on diastolic blood likely due to the inclusion of Pépin 2016 which showed a more
pressure than variation in effect size between the studies (Summary attenuated effect of fixed CPAP on diastolic blood pressure. Similar
of findings for the main comparison). to our analysis, Ip 2012 had insufficient confidence in this effect. Liu
2017 reported no difference in the effects of fixed CPAP and auto-
Potential biases in the review process CPAP on 24-hour diastolic, 24-hour systolic, diurnal systolic, diurnal
Before updating this review we made a number of changes to diastolic, nocturnal systolic or nocturnal diastolic blood pressure
the methods that we had previously implemented (see Differences in direct pair-wise comparisons; office diastolic blood pressure was
between protocol and review). We decided to combine data from not included in this analysis. Interestingly, Liu 2017 ranked fixed
parallel and cross-over studies for the 2019 update of the review. CPAP above auto-CPAP in its likelihood to reduce diurnal systolic
We acknowledge that this decision could introduce methodological (67.44% versus 45.21%) diurnal diastolic (58.75% versus 29.37%),
variation by combining data from short-term within-participant nocturnal systolic (63.1% versus 45.93%) and nocturnal diastolic
studies with parallel group studies that have a longer-term follow- blood pressure (62.76% versus 32.57%), although no assessment of
up where between-participant differences could attenuate over the certainty of this evidence was provided.
time. We used adjusted data, where possible, to account for the
within-person design of cross-over studies. However, for a number One meta-analysis has been published comparing flexible titration
of analyses of 'Summary of findings' table outcomes, we used modalities of CPAP with fixed CPAP (Bakker 2011). Despite some
unadjusted data (Analysis 1.1; Analysis 1.7; Analysis 1.12; Analysis methodological differences relating to the eligibility of short-term
1.14; Analysis 3.1; Analysis 3.2; Analysis 3.6; Analysis 4.1; Analysis studies and separation of parallel and cross-over studies, the effect
4.4). It is possible that individual study weights are artificially low sizes for machine usage and AHI are similar to our own.
without a reasonable estimate of the within-person correlation.
AUTHORS' CONCLUSIONS
The impact of this approach on the summary effect estimates is
small, since only 10% to 15% of total sample size are affected across Implications for practice
the analyses, and the direction and size of effect of the studies
affected are aligned with the summary effect sizes. The consistent In adults with moderate to severe sleep apnoea who are
direction and size of effect for usage, symptom and AHI outcomes starting positive airway pressure therapy, average machine usage
provides some support to our approach in combining the study is probably increased by about 13 minutes per night with
designs and adjustment of the cross-over studies. automatically adjusting continuous positive airway pressure (auto-
CPAP) compared with fixed CPAP (moderate-certainty evidence),
although we do not have enough evidence to determine whether
Informed decisions.
either device leads to more people using machines for four hours 4. We are aware of one large completed study (N = 800)
or more (low certainty). The reduction in daytime sleepiness comparing auto-CPAP and fixed CPAP, which we expect to
associated with the average increased use of auto-CPAP is small incorporate in future versions of this review when its results
(moderate-certainty evidence), and fixed CPAP is slightly more are available (NCT02749812). Two smaller ongoing studies
effective at reducing the Apnoea Hypopnoea Index (AHI) (high- are addressing similar outcomes to those already addressed
certainty evidence). Most of the studies to date have followed (ACTRN12618000379213p; NCT03428516). Future studies should
participants for shorter than 12 weeks. It is unclear whether include longer-term follow-up and measure quality of life.
modifying pressure in participants with mild and less pronounced 5. We have identified one ongoing study of
sleep apnoea symptoms is beneficial. About 25% of people CPAPexp (NCT01753999), and large multicentre studies in bilevel
recruited to the studies are female. Generally, research to date has positive airway pressure (bi-PAP), CPAPexp, humidification and
not addressed what interventions are effective in people who find automatically adjusting CPAP with expiratory pressure relief
CPAP difficult to tolerate. (auto-CPAPexp) are warranted.
6. Studies should better report design features (e.g. blinding and
Use of specific quality of life instruments in the studies to date
allocation concealment) and be more explicit about handling
has been limited, although where they have been used the effect
data from participants who do not continue to use machines
sizes have not exceeded clinically important differences. Evidence
during the studies.
for blood pressure outcomes is insufficient to determine the
anti-hypertensive effects between the different machine types. 7. Given the range of treatment options that continue to emerge,
Tolerabillty outcomes were measured too inconsistently to further head to head comparisons between different ways of modifying
our understanding of how varying treatment pressure with auto- pressure would help to inform choice of treatment where
CPAP changes the experience of applying positive airway pressure. alternatives to fixed CPAP are being considered. Such
studies could also serve as a basis for a network meta-
The evidence base for the remaining interventions included in analysis of pressure modification strategies, including a cost-
the review is smaller, with a similar focus on machine usage effectiveness assessment to inform local decision making.
and symptoms over quality of life. The effect on machine usage
with expiratory pressure CPAP (CPAPexp) is uncertain and there ACKNOWLEDGEMENTS
is little or no difference in symptoms when compared with fixed
CPAP. Although there is some evidence of higher machine usage The Background and Methods sections of this review are based on
following the addition of humidification, the certainty of evidence a standard template used by Cochrane Airways.
is low, and the effects on symptoms and tolerability are uncertain.
This project was supported by the National Institute for Health
Effects of humidification may also be affected by local ambient
Research (NIHR), via Cochrane Infrastructure funding to the
humidity.
Cochrane Airways Group. The views and opinions expressed therein
Implications for research are those of the authors and do not necessarily reflect those of
the Systematic Reviews Programme, NIHR, National Health Service
Study investigators and research funders initiating further (NHS), or the Department of Health.
research in this area should address the following issues related to
the design, analysis and reporting of studies. We are grateful to previous author Muzlifah Hanifa who initiated the
protocol and was involved with study assessment, data collection
1. To date, only a small proportion of eligible trials have recruited and entry, and drafting of the discussion and conclusions. We
people who have been unable to persist with CPAP. Further are very grateful to the members of the Cochrane Airways Group
trials in this population are needed to inform decisions between editorial base who gave support with searching for studies, and
alternative management strategies where acceptability of CPAP to Prof John Wright for constructive comments on the protocol
is lower than in the populations recruited to studies in this and the review on previous versions of the review. We are grateful
review. for assistance given to us by study investigators who provided
2. Assessment of the effects of different pressure machines additional information about their studies: Konrad Bloch (Bloch
in studies that recruit a greater proportion of women and 2018), Atul Gulati (Gulati 2015), Jessie Bakker (Bakker 2010),
participants with lower AHIs than those in the existing studies Naricha Chirakalwasan (Soudorn 2016), Evan Chang (Chang 2015),
would broaden the applicability of the evidence base. Timon Fabius (Rohling 2011), Domagoj Damjanovic (Damjanovic
3. Adoption of a standardised approach to defining machine 2009), Maik Schroder (Nilius 2006), Silke Ryan (Ryan 2009),
tolerability is needed. Variation in the definition and Nathalie Arnol and Jean-Louis Pepin (Pépin 2009; Pépin 2016),
measurement of machine tolerability has made it challenging Christopher Worsnop (Worsnop 2010), Alexander Blau (Blau 2012),
to evaluate the harms from using different pressure modes, Leon Rosenthal (Dolan 2008), Marie-Pia d'Ortho (d'Ortho 2000),
and to determine their relationship with machine usage. Nat Marshall (Marshall 2008), Adrian Kendrick (Kendrick 2002),
Agreement on consistent approaches to measuring mask leak, Clifford Massie (Massie 1999; Massie 2003), Nancy Gordon (Massie
pressure tolerance, and oral and nasal symptoms would 1999; Massie 2003), Sophie West and John Stradling (West 2006),
help decision-makers to balance benefits with harms from Geraldine Lawless (Nolan 2007), Doug McEvoy (Morton 2001),
different treatment options available. Consensus on which Winfried Randerath (Randerath 2001), Frederic Sériès (Meurice
blood pressure parameters to measure is needed in order to 1996; Sériès 1997; Sériès 2001; Meurice 1998), Peter Cistulli
better understand the relationship between blood pressure and (Jarvis 2006), David Hui (To 2008) and Jean-Claude Meurice
long-term cardiovascular outcomes. (NCT02749812).
Informed decisions.
The authors and CRG Editorial Team are grateful to the following 3. PR Srijithesh, National Institute of Mental Health and
peer and consumer reviewers for their time and comments. Neurosciences, Bangalore, Karnataka, India.
4. Jose-Ramon Rueda, University of the Basque Country, Lejona,
1. Hayley Barnes, The Alfred Hospital, Melbourne. Spain.
2. Nathaniel Marshall, University of Sydney and the Woolcock 5. Ndi Euphrasia Ebai-Atuh, Consumer Reviewer, Cameroon.
Institute for Medical Research, Sydney.
Informed decisions.
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conventional CPAP. Sleep 2007;30(Suppl):A185. patients. www.abstracts-on-line.com/abstracts/ATS 2002; Vol.
D26:poster 910.
Gonzalez-Moro 2005 {published data only}
Wiltshire N, Harper A, Buchanan F, Catterall JR, Kendrick AH.
Gonzalez-Moro JMR, Hernandez-Vazquez J, de Lucas-Ramos P,
Autotitrating versus fixed pressure continuous positive airway
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of patients with obstructive sleep apnea syndrome (OSAS) and
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obesity hypoventilation syndrome (OHS): CPAP vs BIPAP: a
short term study [Abstract]. American Thoracic Society 2005 Konermann 1998 {published data only}
International Conference; May 20-25; San Diego. 2005:C29;
Konermann M, Sanner BM, Vyleta M, Laschewski F, Groetz J,
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Sturm A, et al. Use of conventional and self-adjusting nasal
Gulati 2015 {published data only} continuous positive airway pressure for treatment of severe
obstructive sleep apnea syndrome. Chest 1998;113(4):714-8.
Gulati A, Oscroft N, Chadwick R, Ali M, Smith I. The impact
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Meurice JC, Paquereau J, Tamisier R, Levrat V, Pepin JL.
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Powell 2012 {published data only}
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Powell ED, Gay PC, Ojile JM, Litinski M, Malhotra A. A pilot
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Noseda 2004 {published data only} Randerath 2001 {published and unpublished data}
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Randerath WJ, Schräder O, Galetke W, Rühle K-H. A prospective
Nussbaumer 2006 {published data only} randomised cross-over study on the effects acceptance
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airway pressure in home treatment of sleep apnea. Chest European Respiratory Journal 2000;16(Suppl 31):508s.
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Reeves-Hoché 1995 {published data only}
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Resta O, Carratu P, Depalo A, Giliberti T, Ardito M, Marrone O,
Patruno V, Cazzola K, Vicenzi A, Porta A, Tobaldini E, Aiofi S, et et al. Effects of fixed compared to automatic CPAP on sleep in
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Sleep 2005;28:A169. Rochford 2006 {published data only}
Rochford PD, Collins AL, Howard ME, Pierce PJ. Comparison of
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et al. Pressure reduction during exhalation in sleep apnea
patients treated by Continuous positive airway pressure (CPAP). Rohling 2011 {published data only}
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automatic positive airway pressure therapy in OSAS patients.
* Pépin JL, Muir JF, Gentina T, Dauvilliers Y, Tamisier R, European Respiratory Journal 2011;38 (Suppl 55):711s.
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Informed decisions.
Rostig 2003 {unpublished data only} Teschler 2000 {published data only}
* Rostig S, Synofik C, Peter JH, Vogelmeier C, Becker HF. Teschler H, Wessendorf TE, Farhat AA, Konietzko N, Berthon-
[B026] [Poster: 707] Auto-adjusting versus conventional nCPAP Jones M. Two months auto-adjusting versus conventional
therapy in obstructive sleep apnea patients with low treatment nCPAP for obstructive sleep apnoea syndrome. European
compliance. www.abstracts2view.com. 2003. Respiratory Journal 2000;15(6):990-5.
Rostig S, Synofzik C, Peter JH, Vogelmeier C, Becker HF. Auto- To 2008 {published data only}
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patients with low treatment compliance [Abstract]. Sleep randomized cross-over study of auto-continuous positive
Medicine 2003;4(Suppl 1):S40. airway pressure versus fixed-continuous positive airway
pressure in patients with obstructive sleep apnoea. Respirology
Ruhle 2011 {published and unpublished data}
2008;13(1):79-86.
Nilius G, Franke KJ, Domanski U, Ruehle KH. Prospectively
randomised comparison of CPAP without and with controlled To KW, Chan WC, Choo KL, Wong KK, Hui DSC. Randomized
heated humidification with tube heater. European Respiratory prospective cohort of auto continuous positive airway pressure
Journal 2007;30 (Suppl 51):265s. (auto-CPAP) versus fixed continuous positive airway pressure
(Fixed-CPAP) in Chinese patients with obstructive sleep apnea.
* Ruhle KH, Franke KJ, Domanski U, Nilius G. Quality of life, American Thoracic Society International Conference; May 19-24;
compliance, sleep and nasopharyngeal side effects during CPAP San Diego, California. 2006:A868.
therapy with and without controlled heated humidification.
Sleep and Breathing 2011;15(3):479-85. [PUBMED: 20503074] Vennelle 2010 {published and unpublished data}
Vennelle M, White S, Riha RL, Mackay TW, Engleman HM,
Ryan 2009 {published and unpublished data}
Douglas NJ. Randomized controlled trial of variable-pressure
Ryan S, Doherty LS, Nolan GM, McNicholas WT. Effects of heated versus fixed-pressure continuous positive airway pressure
humidification and topical steroids on compliance, nasal (CPAP) treatment for patients with obstructive sleep apnea/
symptoms, and quality of life in patients with obstructive hypopnea syndrome (OSAHS). Sleep 2010;33(2):267-71.
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pressure.. Journal of Clinical Sleep Medicine 2009;15(5):422-7.
[PUBMED: 19961025] Wenzel 2007 {published data only}
Wenzel M, Kerl J, Dellweg D, Barchfeld T, Wenzel C, Kohler O.
Senn 2003 {published and unpublished data}
Expiratory pressure reduction (C-Flex method) versus fix CPAP
Senn O, Brack T, Matthews F, Russi EW, Bloch KE. Randomized in the therapy for obstructive sleep apnoea. Pneumologie
controlled cross-over trial of two different auto-CPAP devices 2007;61(11):692-6.
for obstructive sleep apnea therapy. American Thoracic Society
98thI International Conference; 2002 May 17-22; Georgia. 2002; West 2006 {published data only}
Vol. [D26]:[Poster: 912]. West SD, Jones DR, Stradling J. Comparison of three ways to
determine and deliver pressure during nasal CPAP therapy for
* Senn O, Brack T, Matthews F, Russi EW, Bloch KE. Randomized
obstructive sleep apnoea. Thorax 2005;61(3):226-31.
short-term trial of two auto-CPAP devices versus fixed
continuous positive airway pressure for the treatment of sleep West SD, Jones DR, Stradling JR. A comparison of three ways to
apnea. American Journal of Respiratory Critical Care Medicine start nasal continuous positive airways pressure treatment for
2003;168:1506-11. obstructive sleep apnoea [Abstract]. American Thoracic Society
International Conference; May 20-25; San Diego, California.
Sériès 1997 {published and unpublished data}
2005:532.
Sériès F, Marc I. Efficacy of automatic continuous positive
airway pressure therapy that uses an estimated required * West SD, Jones DR, Stradling JR. Comparison of three ways to
pressure in the treatment of the obstructive sleep apnea determine and deliver pressure during nasal CPAP therapy for
syndrome. Annals of Internal Medicine 1997;127(8):588-95. obstructive sleep apnoea. Thorax 2006;61(3):226-31.
Sériès 2001 {published data only} Worsnop 2010 {published and unpublished data}
Series F, Marc I. Importance of sleep stage- and body position- Worsnop C, Miseski S, Rochford P. Humidification of continuous
dependence of sleep apnoea in determining benefits to auto- positive airway pressure treatment in sleep apnoea reduces
CPAP therapy. European Respiratory Journal 2001;18(1):170-5. nasal symptoms [Abstract]. Proceedings of the American
Thoracic Society 2003;3:P178.
Soudorn 2016 {published data only}
Soudorn C, Muntham D, Reutrakul S, Chirakalwasan N. Effect of * Worsnop CJ, Miseski S, Rochford PD. Routine use of
heated humidification on CPAP therapy adherence in subjects humidification with nasal continuous positive airway pressure.
with obstructive sleep apnea with nasopharyngeal symptoms. Internal Medicine Journal 2010;40(9):650-6. [PUBMED:
Respiratory Care 2016;61(9):1151–9. 19460056]
Informed decisions.
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Anderson FE, Kingshott RN, Taylor DR, Jones DR, Kline LR,
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(chinstrap) reduces mouth leak during nasal CPAP. Sleep Boudewyns 1999 {published data only}
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apnea. Sleep and Breathing 2011;15(3):301-9. Bradshaw 2004 {published data only}
Bradshaw DA, Murphy DP, Ruff GA. The effects of oral
Bardwell 2007 {published data only} zolpidem on nasal continuous positive airway pressure (CPAP)
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in patients with obstructive sleep apnea a randomized placebo Brammer 1999 {published data only}
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of fixed pressure CPAP. Thorax 1999;54(Suppl 3):A48 P117.
Informed decisions.
Buyse 2003 {published data only} the cardiovascular risk factors associated with obstructive
Buyse B, Cauberghs M, Demedts M. Comparison of 2 auto sleep apnoea [Abstract]. American Thoracic Society 100th
CPAP algorithms: apnea-hypopnea-flow limitation versus International Conference; 2004 May 21-26; Orlando. 2004:C99
airway impedance [Abstract]. European Respiratory Journal Poster 111.
2003;22(Suppl 45):P670.
Cross 2005 {published data only}
Buyse B, Cauberghs M, Demedts M. Study of 2 auto CPAP's Cross MD, Vennelle M, Engleman HM, Douglas NJ. Predictors of
based on flow limitation but with different working algorithm poor titration and outcome in patients with obstructive sleep
[Abstract]. European Respiratory Journal 2003;22(Suppl apnea/hypopnea syndrome (OSAHS) after home or hospital
45):P669. automated CPAP titration [Abstract]. American Thoracic Society
2005 International Conference; May 20-25; San Diego, California.
Canisius 2007 {published data only} 2005:C58; Poster: C48.
Canisius S, Ploch T, Loh A, Vogelmeier C, Jerrentrup A.
Comparison of therapeutic equivalence of the auto-CPAP device Cumin 2011 {published data only}
'Delphinus' with conventional nCPAP therapy [Vergleich der Cumin D, Whiting D, Malla A, Gerred A, Dungan G. Randomised,
therapeutischen Äquivalenz des automatischen nCPAP-Gerätes cross-over evaluation of a novel implementation of pressure
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Somnologie 2007;11(1):28-34. Medicine. 2011; Vol. 12 (Suppl 1):S75.
Jerrentrup L, Canisius S, Wilhelm S, Kesper K, Ploch T, Damjanovic 2005 {published data only}
Vogelmeier C, et al. Work of breathing in fixed and pressure Damjanovic D, Fluck A, Idzko M, Muller-Quernheim J,
relief continuous positive airway pressure (C-Flex™): a post hoc Sorichter S. Nasal CPAP in the therapy of OSAS - does a closer
analysis. Respiration 2017;93:23-31. patient guidance and support increase compliance?. European
Respiratory Journal 2005;26(Suppl 49):4521.
Chan 2004 {published data only}
Chan J, Tedjasaputra I, Chan CS. Improving CPCP compliance Delwiche 2003 {published data only}
and patient comfort with the mirage ACTiva system [Abstract]. Delwiche JP, Evrard G, Delaunois L. Auto nCPAP or not auto
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2004 May 21-26; Orlando. 2004:C65 Poster K3. 45):P675.
Chervin 1997 {published data only} Dungan 2010 {published data only}
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patients. Sleep and Biological Rhythms 2010;8:A79.
Chihara 2012 {published data only}
Chihara Y, Tsuboi T, Hitomi T, Azuma M, Murase K, Toyama Y, Duntley 2005 {published data only}
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CPAP [Abstract]. Sleep 2005;28:A182.
Chihara Y, Tsuboi T, Hitomi T, Azumi M, Murase K, Toyama Y,
et al. Flexible positive airway pressure improves treatment Duoung 2005 {published data only}
adherence compared with auto-adjusting PAP. European
Duong M, Jayaram L, Camfferman D, Catcheside P, Mykytyn I,
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Colrain 2007 {published data only} titration in obstructive sleep apnoea syndrome. European
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* Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Bakker 2010
Methods Randomised, double-blind, parallel group study
Participants N = 76 participants (53 M/23 F). Age not reported. BMI 35.6 kg/m2; AHI 60.2; ESS 13.6
Inclusion criteria: CPAP naive
Exclusion criteria: significant cardiac, respiratory, psychiatric, or sleep comorbidities
Interventions CPAP versus C-Flex (identical devices)
Study duration: 3 months
Outcomes 1. Machine usage (average hours used and average days used)
2. Quality of life (FOSQ and SF-36)
3. AHI
4. Symptoms (ESS)
5. Withdrawals
6. Treatment pressure
7. Tolerability (mask leak)
Funding & conflicts of in- 'This study was funded by Philips-Respironics. All authors received research support from Philips-
terest statements Respironics. Philips-Respironics manufactures and markets CPAP and C-Flex devices.'
Notes
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Low risk Quote: "Randomization to treatment was performed prior to manual titration
tion (selection bias) using a (1, 2) urn randomization procedure"
Allocation concealment Low risk Quote: "Randomization to treatment was performed prior to manual titration
(selection bias) using a (1, 2) urn randomization procedure"
Informed decisions.
Bakker 2010 (Continued)
Blinding of participants Low risk Quote: "The study was a double-blinded, parallel-arm RCT of C-Flex versus
and personnel (perfor- CPAP"
mance bias)
Machine usage, symp- Quote: "Patients were not able to access the C-Flex menu option, and all refer-
toms, quality of life, with- ences to "C-Flex" on the device were covered"
drawal, adverse effects
Blinding of participants Low risk Quote: "The study was a double-blinded, parallel-arm RCT of C-Flex versus
and personnel (perfor- CPAP"
mance bias)
AHI, blood pressure, treat- Quote: "Patients were not able to access the C-Flex menu option, and all refer-
ment pressure ences to "C-Flex" on the device were covered"
Blinding of outcome as- Low risk Identical machine appearance unlikely to affect measurement of these out-
sessment (detection bias) comes
Machine usage, symp-
toms, quality of life, with-
Blinding of outcome as- Low risk Quote: "The data analyst remained blinded by random 3-digit codes being as-
sessment (detection bias) signed to all patients"
AHI, blood pressure, treat-
ment pressure
Incomplete outcome data Low risk Quote: "Two patients were withdrawn".........2 patients dropped out of the
(attrition bias) CPAP group............they were replaced with additional recruitment, and there-
All outcomes fore analysis was conducted on a per-protocol basis"
Selective reporting (re- Low risk All outcomes reported

porting bias)
Other bias Low risk No concerns identified
Ballard 2007
Methods Randomised, double-blind, parallel group trial
Participants N = 104 participants (67 M/37 F); Age 52 years; BMI 33 kg/m2; AHI 42; ESS not reported
Inclusion criteria: non-adherent with CPAP based on 14-day run-in (< 4 hours/day); previous diagnosis
of OSA
Exclusion criteria: compliant with CPAP during run-in
Interventions Bi-PAP with flexible pressure setting versus fixed CPAP setting (identical machine)
Run-in: phase 1 of study identified non-adherent CPAP users (those using CPAP < 4 hours/day)
Study duration: 12 weeks
Outcomes 1. Machine usage (average hours used and using therapy > 4 hrs)
2. Quality of life (FOSQ)
Funding & conflicts of in- Quote: "This study was supported by a grant from Respironics, Inc. Respironics reimbursed National
terest statements Jewish Medical and Research Center for part of Dr. Ballard’s time. Dr. Gay has received research sup-
port from ResMed. Dr. Strollo has indicated no financial conflicts of interest."
Informed decisions.
Ballard 2007 (Continued)
Notes
Risk of bias
Random sequence genera- Unclear risk Quote: "Patients were then provided a modified positive airway pressure de-
tion (selection bias) vice (BiPAP Pro, Respironics Inc.) randomly set to either CPAP or BiFlex mode
at appropriate pressure(s)"
Allocation concealment Unclear risk Quote: "Patients were then provided a modified positive airway pressure de-
(selection bias) vice (BiPAP Pro, Respironics Inc.) randomly set to either CPAP or BiFlex mode
at appropriate pressure(s)"
Blinding of participants Low risk Quote: "Both patients and the investigators were blinded as to the specific
and personnel (perfor- mode assigned to each patient."
mance bias)
Blinding of participants Low risk Quote: "Both patients and the investigators were blinded as to the specific
and personnel (perfor- mode assigned to each patient."
mance bias)
ment pressure
sessment (detection bias) comes.
ment pressure
Incomplete outcome data Unclear risk Study reported to have been analysed on ITT principles. Unlikley to bias ma-
(attrition bias) chine usage data but quality of life collected from completers. There was dif-
All outcomes ferential dropout and this may have influenced the results.
Selective reporting (re- Unclear risk Insufficient information available

porting bias)
Berry 2014
Methods Randomised, open-label, parallel group, singe-centre trial
Participants N = 156 participants (145 M/11 F). Age: 59 years; BMI: 36 kg/m2; AHI: 28.5 ESS: 14.8
Inclusion criteria: AHI ≥ 10/hour; ESS ≥ 8; living within 200 miles of treatment centre; age > 18 years
Informed decisions.
Berry 2014 (Continued)

Exclusion criteria: previous CPAP therapy; shift work; unstable depression/psychosis; non-adherence
with medication; COPD; uncontrolled hypertension or restless legs syndrome; narcolepsy; supplemen-
tal oxygen use; congestive heart failure; nightly narcotic use; hypoventilation; neuromuscular weak-
ness; regular sleep of < 4 hours per night; low baseline SaO2; central apnoea index > 5/hour
Interventions Auto-CPAP versus home PSG CPAP titration followed by fixed pressure CPAP treatment
Outcomes 1. Machine usage (average hours used)

2. AHI
3. Symptoms (ESS)
6. Withdrawals
Funding & conflicts of in- Quote: "This study was supported by a research grant from the Res Med Foundation and an unrestrict-
terest statements ed research grant from Philips Respironics. Both grants were made to the North Florida Foundation for
Research and Education. The CPAP and APAP equipment were purchased by the VA as part of the rou-
tine clinical care of the patients. The PAP setups were performed by clinical PAP respiratory therapists
as part of the patient’s usual care. A registered polysomnographic technologist (CPAP titrations) and
study coordinator were paid by research funding. The principal investigators received no salary sup-
port from research funding. This work was also supported by resources provided by the North Flori-
da/South Georgia Veterans Health System, Gainesville, FL. The contents of this paper do not repre-
sent the views of the U.S. Department of Veterans Affairs or the United States Government. The authors
have indicated no other financial conflicts of interest. The study was performed at the Malcom Randall
VA Medical Center, Gainesville, FL."
Notes
Risk of bias
Random sequence genera- Unclear risk Insufficient details available to determine process
tion (selection bias)
Allocation concealment Low risk Quote: "The method of randomization was by opening sequential envelopes
(selection bias) prepared by the research service."
Blinding of participants High risk Study had open-label design which likely affects usage, symptoms, quality of
and personnel (perfor- life attrition outcomes.
mance bias)
Blinding of participants Low risk These outcomes unlikely to be affected by open-label design.
and personnel (perfor-
mance bias)
ment pressure
Blinding of outcome as- High risk Impact of study design on outcome assessment related to nature of outcome.
sessment (detection bias) Usage, AHI and treatment pressure measured from technical readings. Symp-
Machine usage, symptoms, quality of life more likely affected by open-label design.
Informed decisions.
Berry 2014 (Continued)
Blinding of outcome as- Low risk Treatment pressure and AHI unlikely to be affected by open-label design.
sessment (detection bias)
ment pressure
Incomplete outcome data Unclear risk Balanced but potentially meaningful dropout which was slightly higher in fixed
(attrition bias) CPAP group (19/78 versus 12/78). Participants not using machines at clinic visit
All outcomes assumed to be non-users and assigned values of 0 for usage outcome. Likely to
be greater impact on symptoms and quality of life outcomes.
Selective reporting (re- Low risk All prespecified outcomes presented according to details provided on trials
porting bias) registry record.
Blau 2012
Participants N = 35 participants (34 M/1 F); Age 54.2 years; BMI 30.9 kg/m2; AHI ≥ 39; ESS: 10.2
Inclusion criteria: 18 to 75 years; AHI ≥ 15; BMI < 45 kg/m2; ability to follow study specific instructions
Exclusion criteria: other sleep, cardiac, pulmonary, psychiatric or neurological disorder; previous
abuse of alcohol, hypnotics or drugs; previous treatment for OSA (including CPAP); inability to wear a
mask
Interventions ABRP-PAP versus fixed CPAP

2. AHI
3. Symptoms (ESS)
4. Withdrawals
Funding & conflicts of in- Quote: "This study was supported by an unrestricted grant from Philips Respironics, Inc. 1001 Murry
terest statements Ridge Lane, Murrysville, PA, 15668, USA"
Conflict of interest quote: "'Dr. Fietze, Prof. Penzel, Dr. Peter and Dr. Blau have received travel grants
and honorariums for lecturing from Philips Respironics. The other authors have no significant conflicts
of interest with any companies/organizations whose products or services may be discussed in this arti-
cle."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "We generated a list of N = 32 uniformly distributed pseudo-random
tion (selection bias) numbers of either 0 (CPAP) or 1 (Auto bi-level) by using the Mersenne Twister
algorithm"
Informed decisions.
Blau 2012 (Continued)
Allocation concealment Low risk Quote: "The allocation of the patient was told directly via telephone in case of
(selection bias) randomisation from an not otherwise involved team member, situated in an-
other campus of our university clinic."
Blinding of participants Low risk Quote: "Devices were set by the study coordinators who deactivated the LCD
and personnel (perfor- display so that the patient and investigators did not become aware of device
mance bias) allocation"
toms, quality of life, with- Quote: "There were no concrete information about characteristics of these dif-
drawal, adverse effects ferent PAP types in the informed consent"
Blinding of participants Low risk Quote: "Devices were set by the study coordinators who deactivated the LCD
and personnel (perfor- display so that the patient and investigators did not become aware of device
mance bias) allocation"
ment pressure
Blinding of outcome as- Low risk Quote: "The investigator making and analysing the PSG recordings on thera-
sessment (detection bias) py and other outcome measures did not have access to information from the
Machine usage, symp- therapy device within their PSG montage"
ment pressure
Incomplete outcome data Unclear risk 3 withdrawals after allocation (1 from CPAP group and 2 from ABRP-PAP
(attrition bias) group); these patients were not included in analysis.
All outcomes

porting bias)
Bloch 2018
Participants N = 208 participants (177 M/31 F). Age 55.5; BMI 32.7 kg/m2; AHI 48.4; ESS 13
Inclusion criteria: ESS ≥ 8; AHI ≥ 10/hour; age 18-75
Exclusion criteria: psychophysiological incapacity to perform questionnaires, other sleep disorders,

psychiatric disease, previous CPAP therapy, previous uvulopalatopharyngoplasty, chronic nasal ob-
struction, cancer, COPD, with FEV1 < 50% predicted, symptomatic cardiovascular disease, previous
stroke, cheyne-Stokes respiration, chronic pain syndromes, fibromyalgia, drug or alcohol addiction
Interventions Auto-CPAP versus fixed CPAP
Study duration: 2 years

2. Symptoms (ESS)
Informed decisions.
Bloch 2018 (Continued)

3. AHI
4. Quality of life (SF-36, FOSQ)
6. Blood pressure
7. Adverse events
Funding & conflicts of in- Quote: "The study was supported by the Swiss National Science Foundation, the lung leagues of Zurich,
terest statements St. Gallen and Thurgau and by unconditional grants from the respironics Foundation and resMed
Switzerland. This was an investigator initiated trial, and the commercial companies were not involved
in study design, data acquisition and analysis or writing the manuscript. competing interests KEB re-
ports grants to his institution from Swiss National Science Foundation, Zurich lung league, respironics
Foundation, resMed Switzerland, during the conduct of the study. The other authors report no compet-
ing interests."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation of participants was performed according to a 1:1 bal-
tion (selection bias) anced block design by the study centre.......envelopes containing codes for
the treatment mode and CPAP brand for 12-24 participants were sent to par-
ticipating centres as needed. The local co-ordinator drew a paper (from an
opaque envelope) with the codes for each participant."
Allocation concealment Low risk Quote: "...envelopes containing codes for the treatment mode and CPAP brand
(selection bias) for 12-24 participants were sent to participating centres as needed. The local
co-ordinator drew a paper (from an opaque envelope) with the codes for each
participant."
Blinding of participants High risk Quote: "True blinding of participants and clinical care-givers was not feasible
and personnel (perfor- since all participants had an initial phase of autoCPAP therapy." This is likely
mance bias) to impact on usage data, quality of life and symptom scores.
Blinding of participants Low risk Identical machine appearance unlikely to affect measurement of these out-
and personnel (perfor- comes.
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "True blinding of participants and clinical care-givers was not feasible
sessment (detection bias) since all participants had an initial phase of autoCPAP therapy." This is likely
Machine usage, symp- to impact on usage data, quality of life and symptom scores
ment pressure
Incomplete outcome data Unclear risk 15 out of 95 randomised to fixed CPAP group withdrew from treatment by 24
(attrition bias) months. 21 out of 113 randomised to auto-CPAP group withdrew from treat-
All outcomes ment by 24 months. Data were presented for ITT analysis and per protocol.
Multiple imputation method used to address attrition. In view of large attrition
Informed decisions.
Bloch 2018 (Continued)

rates there is some uncertainty over the reliability of data for usage, symptoms
and quality of life. Treatment pressure and AHI unlikely to have been affected
since short term measurement is informative in determining intervention ef-
fects.

porting bias)
Bogan 2017
Methods Randomised cross-over study. Data analysed with paired t tests.
Participants N = 70 participants (48 M/22 F); age: 50.78; BMI: 35.93; AHI: not reported. ESS: 10.7
Inclusion criteria: 18 to 75 years of age; AHI ≥ 10 per hour; successful in-lab polysomnography; seven
hours’ sleep on most nights; bedtime midnight or earlier; fluent English speakers
Exclusion criteria: use of CPAP in last 2 years; CPAP therapy contraindicated; factor or disease that
might interfere with study participation (e.g. psychiatric disease, non-adherence to medical regimens);
significant sleep disorder(s) that make use of CPAP challenging; use of hypnotics and/or sedating med-
ications; surgery of the mouth, nose, sinuses, or airways in previous 12 months; patients who are re-
quired by the nature of their employment to not comply with therapy (e.g. truck drivers, airline pilots)
Interventions Fixed CPAPexp designed to detect transition from sleep to wakefulness versus fixed pressure CPAP
Duration: 4 weeks per treatment arm
Outcomes 1. Machine use (average hours used last 2 weeks of treatment)

2. Symptoms (ESS)
3. Quality of life (Short form FOSQ)
4. AHI
5. Mask leak
Funding & conflicts of in- Quote: "The authors declare that there are no conflicts of interest regarding the publication of this pa-
terest statements per. Dr Chris Frampton is an independent, statistical consultant hired to analyse the results for this
study. Medical writing assistance was provided by Anita Fitzgerald, on behalf of Fisher & Paykel Health-
care. Irene Cheung is an employed staff from Fisher & Paykel Healthcare who helped in inputting data."
Study sponsored by Fisher & Paykel, manufacturers' of SensAwake expiratory relief
Notes The type of expiratory pressure relief mechanism used in this study works differently to those evaluat-
ed by other studies in this review. We present the findings of this study separately to analyses of CPAP
expiratory pressure relief devices.
Risk of bias
Random sequence genera- Low risk Quote: "Random permuted blocks were used to randomise patients into the
tion (selection bias) two treatment sequence groups."
Allocation concealment Low risk Quote: "The randomization records were kept in a patient master log. The
(selection bias) study coordinator set the device to the appropriate treatment arm according
to the patient master log during the device
Informed decisions.
Bogan 2017 (Continued)

setup visit."
The process described is consistent with an approach that conceals the assign-
ment from both the study personnel and the participants and so is probably
adequate.
Blinding of participants Low risk Quote: "Both the physician and the patient were blinded to the treatment. To
and personnel (perfor- ensure adequate blinding, SensAwake was turned ON in all devices and this
mance bias) setting displayed to the user."
Blinding of participants Low risk Quote: "Both the physician and the patient were blinded to the treatment. To
and personnel (perfor- ensure adequate blinding, SensAwake was turned ON in all devices and this
mance bias) setting displayed to the user."
ment pressure
ment pressure
Incomplete outcome data High risk 5 participants withdrew before completion of both arms. Data on machine us-
(attrition bias) age available for participants who completed both arms.
All outcomes
Selective reporting (re- Low risk Outcomes reported in accordance with trial protocol.
porting bias)
Other bias Low risk No significant concerns identified.
Castronovo 2006
Methods Randomised, cross-over study. Statistical analysis approach not described
Participants N = 50 participants. 40 completed and analysed. Age: 53 years. No other baseline details reported.
Inclusion criteria: severe OSA (RDI > 30)
Interventions Auto-CPAP versus fixed CPAP (RemStar machines set in 2 different modes)
Study duration: 2 x 4 weeks
Outcomes 1. Neurocognitive function

2. Machine usage (average hours used)
3. Symptoms (ESS)
Informed decisions.
Castronovo 2006 (Continued)
Funding & conflicts of in- Details not available (conference abstract)

terest statements
Notes TJL wrote for confirmation of data and methods on 3 September 2008
Risk of bias
Random sequence genera- Unclear risk Information not available

Allocation concealment Unclear risk Information not available

(selection bias)
Blinding of participants Unclear risk Information not available

mance bias)

mance bias)
ment pressure
Blinding of outcome as- Unclear risk Quote: "Global cognitive functioning, attention, vigilance, language, memo-
sessment (detection bias) ry.......were blindly assessed."
toms, quality of life, with- No further information available to judge this
Blinding of outcome as- Unclear risk Information not available

ment pressure
Incomplete outcome data High risk 20% attrition. Non-completers not analysed
(attrition bias)
All outcomes
Selective reporting (re- Unclear risk Results reported in abstract form. Not all outcomes reported
porting bias)
Other bias Unclear risk Information not available
Chang 2015
Methods Prospective, randomised, cross-over study. Statistical analysis methods unclear
Participants N = 19 participants (18 M/1 F). Age 46.2; BMI 30.2; AHI 59.7; ESS 9.6
Inclusion criteria: age > 20, AHI > 15, consent to wear CPAP
Informed decisions.
Chang 2015 (Continued)

Exclusion criteria: not consenting to positive pressure device, treatment for mood disorders such as
anxiety and depression
Outcomes 1. Machine usage (average hours used & average days used)
2. Quality of life (SF-36)
3. AHI
Funding & conflicts of in- Funding not declared. Conflict of interest: none
terest statements
Notes Unadjusted values used in the analysis as the P values were high and errors were very small.
Risk of bias
Random sequence genera- Unclear risk Quote: "We used single sequence of random assignments for randomisation."
tion (selection bias) Not clear how sequence was generated.
Allocation concealment Unclear risk Quote: "There was no selection bias if the patient wanted to enrol in our
(selection bias) study." Not clear how allocation was concealed from study personnel or partic-
ipants
Blinding of participants High risk Study was not blinded

mance bias)
Blinding of participants Low risk These outcomes unlikely to be affected by awareness of treatment group.
mance bias)
ment pressure
Blinding of outcome as- High risk Study was not blinded

Blinding of outcome as- Low risk These outcomes unlikely to be affected by awareness of treatment group.
ment pressure
Incomplete outcome data High risk Quote: "Six of the 25 enrolled OSA patients (24%; 3 received APAP first and
(attrition bias) three received CPAP first) withdrew during the first month due to intolerance
All outcomes to CPAP/APAP."

porting bias)
Informed decisions.
Chang 2015 (Continued)
d'Ortho 2000
Methods Randomised, single-blind, cross-over study. Method of randomisation: random sampling number ta-
bles (correspondence with trialist). All participants accounted for
Data analysis: paired t test where ANOVA significant. T test used for treatment pressure. Analysis on us-
age not paired t test.
Participants N = 25 participants (22 M/3 F). Mean age 57; mean AHI 57.8
Inclusion criteria: OSA confirmed by PSG; AHI > 10/hr; ATS recommended indication for CPAP treat-
ment
Interventions Auto-CPAP versus fixed CPAP. No washout period
Study duration: 2 x 4 week treatment arms

2. AHI
4. Tolerance to CPAP (questionnaire scoring system)
5. Symptoms (ESS)
6. Preference
Funding & conflicts of in- Funded by Institut National de la sante et de la Recherche Medicale & by Nellcor-Puritan Bennett. No
terest statements declaration of interests provided.
Notes —
Risk of bias
Random sequence genera- Low risk Random sampling number tables


(selection bias)
Blinding of participants High risk Quote: "Patients were not aware of the order of administration (i.e. they were
and personnel (perfor- blinded to the setting mode until the first night of use after which they could
mance bias) easily guess which mode they were using.).........The questionnaire was com-
Machine usage, symp- pleted with the help of sleep laboratory technicians who were unaware of
toms, quality of life, with- CPAP mode."
Blinding of participants Low risk Awareness of treatment group assignment unlikely to affect objective out-
and personnel (perfor- come data from the study
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "Patients were not aware of the order of administration (i.e. they were
sessment (detection bias) blinded to the setting mode until the first night of use after which they could
Informed decisions.
d'Ortho 2000 (Continued)

Machine usage, symp- easily guess which mode they were using.).........The questionnaire was com-
toms, quality of life, with- pleted with the help of sleep laboratory technicians who were unaware of
drawal, adverse effects CPAP mode."
Blinding of outcome as- Low risk Awareness of treatment group assignment unlikely to affect objective out-
sessment (detection bias) come data from the study
ment pressure
Incomplete outcome data Low risk All participants accounted for

(attrition bias)
All outcomes

porting bias)
Damjanovic 2009
Methods Randomised controlled, parallel group trial
Participants N = 100 participants (78 M/22 F); mean age 57; BMI 31 kg/m2
Inclusion criteria: AHI > 15, with or without corresponding daytime symptoms
Exclusion criteria: 1. global respiratory failure; 2. central sleep apnoea syndrome; 3. severe mental or
psychological impairment
Interventions 4 groups. Autoadjusting CPAP with or without intensive support versus fixed CPAP with or without in-
tensive support
Outcomes 1. Machine usage (hours of use and % days used)

2. AHI
3. Oxygen desaturation index
4. Symptoms (ESS)
Funding & conflicts of in- Information not available (link to declarations of interest no longer live)
terest statements
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Pulling mixed and sealed envelopes"
Allocation concealment Low risk Quote: "Pulling mixed and sealed envelopes... At time of recruitment, re-
(selection bias) cruiters were also unaware of allocation."
Informed decisions.
Damjanovic 2009 (Continued)
Blinding of participants High risk Quote: "Patients were not told about their pressure mode, however, full blind-
and personnel (perfor- ing of pressure delivery was not possible. At time of recruitment, recruiters
mance bias) were also unaware of allocation."
Blinding of participants Low risk Awareness of treatment group assignment unlikely to affect objective out-
and personnel (perfor- come data from the study
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "Outcome assessors were not blinded"
ment pressure
Incomplete outcome data High risk No information on withdrawals provided

(attrition bias)
All outcomes

porting bias)
Dolan 2008
Methods Randomised, single-blind, parallel group trial. Method of randomisation not reported
Participants N = 184 participants (138 M/46 F); age: 48 years; ESS: 15
Inclusion criteria: newly diagnosed OSA; study participants who used PAP for 4 hours night or more in
the first week of treatment were followed up; AHI > 10; ESS ≥ 10
Exclusion criteria: prior surgical procedure for OSA; significant hypoventilation; CPAP exposure; signif-
icant comorbidities
Interventions CPAP with expiratory pressure relief (C-Flex) versus fixed pressure CPAP

2. Treatment satisfaction (VAS)
3. Symptoms (ESS)
Funding & conflicts of in- This study was funded by Respironics. No author declarations provided.
terest statements
Informed decisions.
Dolan 2008 (Continued)
Notes —
Risk of bias
Random sequence genera- Low risk Quote: "Randomization was centralized by the sponsor. Randomization lists
tion (selection bias) were generated in block sizes of 4 and 6 randomly chosen with respect to or-
der. The actual block size of 10 comprised a block of 4 (or 6) followed by a
block of 6 (or 4). Randomization cards were provided to the clinical sites at the
time of study initiation."
Allocation concealment Low risk Quote: "Research assistants received sealed random condition assignment
(selection bias) cards from Respironics to determine standard CPAP or C-Flex therapy."
Blinding of participants High risk Quote: "Participants were not made aware of the treatment they were as-
and personnel (perfor- signed. This study was therefore a.......single-blinded, controlled study". Only
mance bias) participants were blinded.
Blinding of participants Low risk Study design unlikely to affect these outcomes.
mance bias)
ment pressure
Blinding of outcome as- High risk Study personnel were aware of treatment group assignment as the study was
sessment (detection bias) single-blinded.
Blinding of outcome as- Low risk Study design unlikely to affect these outcomes.
ment pressure
Incomplete outcome data Unclear risk Quote: "Data were analyzed with multivariate mixed models procedures that
(attrition bias) allowed for analysis including participants with missing observations."
All outcomes

porting bias)
Ficker 2003
Methods Randomised, parallel group study. Methods of randomisation not reported. Devices were identical in
appearance.
Participants N = 100 participants. Mean age: 54.3; BMI: 31.8; AHI: 47.9; ESS: 12.6
Inclusion criteria: diurnal somnolence (≥ 8 on ESS); AHI > 10; written consent
Informed decisions.
Ficker 2003 (Continued)

Exclusion criteria: prior CPAP therapy; central sleep apnoea or Cheyne-Stokes respiration; severe
nasal obstruction or other conditions contraindicating CPAP treatment; COPD (FEV1 < 70% predicted);
congestive heart failure (NYHA III or IV)
Interventions Auto-CPAP (forced oscillation technique) versus fixed CPAP
Conference abstract reported 8 weeks duration (published paper reported 2 nights data from laborato-
ry studies)

2. AHI
3. Symptoms (ESS)
Funding & conflicts of in- Not available (conference abstract)

terest statements
Notes
Risk of bias


(selection bias)

mance bias)

mance bias)
ment pressure


ment pressure
Incomplete outcome data Unclear risk Information not available

(attrition bias)
All outcomes
Informed decisions.
Ficker 2003 (Continued)
Selective reporting (re- Unclear risk Information not available

porting bias)
Fietze 2007
Methods Randomised, double-blind, parallel group study. Participants randomised for 2 night cross-over and re-
tained device assigned on second night for subsequent 6-week period.
Participants N = 21 (20 M/1 F) participants. Mean age 54.2; BMI: 30.9 kg/m2. AHI: 41.8. ESS: 12.9
Inclusion criteria: AHI > 10 or excessive sleepiness (if AHI < 10). Participants who did not have exces-
sive sleepiness at baseline also eligible if AHI > 20
Exclusion criteria: other sleep disorders (e.g. restless leg syndrome or periodic leg movement syn-
drome; cardiac, pulmonary or other medical disorders;psychiatric/neurological disorders; abuse of
sleep-inducing agents or other drugs; suspected or confirmed central sleep apnoea syndrome; prior
OSA treatment (e.g. CPAP, oral devices or surgery)
Interventions Auto-CPAP versus fixed pressure CPAP (established by manual titration after 2 night cross-over study)

2. Symptoms (ESS)
4. AHI
Funding & conflicts of in- Funding quote: "This study was supported by an unrestricted grant from Respironics Inc.". No declara-
terest statements tions reported from authors.
Notes
Risk of bias
Random sequence genera- Unclear risk Described as randomised but no further details provided.
Allocation concealment Unclear risk Insufficient information available to allow judgement.

(selection bias)
Blinding of participants Low risk Same device used with different pressure settings (REMstar Auto CPAP).
mance bias)
Blinding of participants Low risk Same device used with different pressure settings (REMstar Auto CPAP).
mance bias)
Informed decisions.
Fietze 2007 (Continued)

ment pressure
Blinding of outcome as- Low risk Adequate blinding procedure in place and unlikely that this has impacted on
sessment (detection bias) subjective outcomes.
Blinding of outcome as- Low risk Adequate blinding procedure in place and unlikely that this has impacted on
sessment (detection bias) objective outcomes.
ment pressure
Incomplete outcome data Low risk All 21 participants who started completed the study.
(attrition bias)
All outcomes
Selective reporting (re- High risk Symptoms and quality of life data measured but reported as aggregate of two
porting bias) treatment groups and described as not significantly different.
Other bias Low risk No concerns identified.
Galetke 2008
Methods Randomised, single-blind, cross-over study (participants not informed of order/setting)
Statistical test: Wilcoxon test
Participants N = 20 participants (16 M/4 F) completed and analysed. Mean age: 56 years. AHI: 33; ESS: 10.3
Inclusion criteria: new diagnosis of OSA (diagnosis established through polysomnography, AHI > 10)
Exclusion criteria: COPD, congestive heart failure and other serious medical disorders
Interventions Auto-CPAP versus fixed pressure CPAP
Same machine delivered the different treatment pressure settings

2. AHI
3. Symptoms (ESS)
4. Tolerability (leak time)
Funding & conflicts of in- Not provided

terest statements
Notes —
Risk of bias
Informed decisions.
Galetke 2008 (Continued)


(selection bias)
Blinding of participants High risk Quote: "a randomized, single-blinded, cross-over study." Only participants
and personnel (perfor- were blinded.
mance bias)
Blinding of participants Low risk These outcomes unlikely to be affected by open-label design.
mance bias)
ment pressure
Blinding of outcome as- High risk Only participants were blinded.

Blinding of outcome as- Low risk These outcomes unlikely to be affected by open-label design.
ment pressure
Incomplete outcome data Low risk All participants completed

(attrition bias)
All outcomes

porting bias)
Gay 2003
Methods Randomised, double-blind, parallel group trial. Machines had settings: 'Set CPAP'; 'Set NBL' and 'A'. As-
sessors could alter the settings for safety reasons. Randomisation not reported
Participants N = 27 participants (22 M/5 F). Age: 44 years; BMI: 35 kg/m2; AHI: 43; ESS: 13.8
Inclusion criteria: > 18 years; AHI > 10 and < 100; ability to follow instructions and provide informed
consent; willingness to return for follow-up visit 30 days after random allocation to CPAP/BiPAP; resi-
dence within 200 miles of clinic
Exclusion criteria: inability to wear a mask; prior surgical treatment for OSA; prior CPAP usage; other
significant comorbidities
Interventions Bi-level PAP versus CPAP. Participants also given instruction via educational video on CPAP and OSA.
Study duration: 30 days
Informed decisions.
Gay 2003 (Continued)

2. Symptoms (ESS)
3. AHI
4. Tolerability
Funding & conflicts of in- Quote: "Dr. Peter Gay received grant support for this study by Respironics Inc. (noted in manuscript)."
terest statements
Notes
Risk of bias

Allocation concealment Low risk Quote: "the technician selected the 'A' mode which in a double-blinded and se-
(selection bias) lective way, locked in the optimal settings for either CPAP or NBL"
Blinding of participants Low risk Quote: "the technician selected the 'A' mode which in a double-blinded and se-
and personnel (perfor- lective way, locked in the optimal settings for either CPAP or NBL.............true
mance bias) identification of the 'A' mode was not revealed until the end of the trial"
Blinding of participants Low risk These outcomes unlikely to be affected by study design.
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "the technician selected the 'A' mode which in a double-blinded and se-
sessment (detection bias) lective way, locked in the optimal settings for either CPAP or NBL.............true
Machine usage, symp- identification of the 'A' mode was not revealed until the end of the trial"
Blinding of outcome as- Low risk These outcomes unlikely to be affected by study design.
ment pressure
Incomplete outcome data Low risk Randomisation was performed prior to baseline PSG, after which a number
(attrition bias) of participants became ineligible. All participants recruited to the 2nd phase
All outcomes completed the study. There were no withdrawals from this study, although the
sample reflects a selected population.
Selective reporting (re- High risk Data on quality of life (FOSQ) were not reported but described as 'equivalent'
porting bias) between two treatment arms.
Informed decisions.
Gfüllner 2007
Methods Randomised, cross-over study. Statistical analysis not clear
Participants N = 18 (15 M/3 F); mean age: 56.8 years; AHI: 41.4; BMI: 36
Inclusion criteria: non-sleepy OSA patients
Interventions Pressure relief CPAP versus fixed CPAP

2. Satisfaction with therapy
3. Symptoms (ESS)

terest statements
Notes TJL emailed for confirmation of methods and data on 4 September 2008
Risk of bias
Random sequence genera- Unclear risk Information not available; requested

Allocation concealment Unclear risk Information not available; requested

(selection bias)

mance bias)

mance bias)
ment pressure


ment pressure

(attrition bias)
All outcomes
Informed decisions.
Gfüllner 2007 (Continued)

porting bias)
Gonzalez-Moro 2005
Methods Randomised parallel group study. Randomisation and blinding not described
Participants N = 20; ESS: 12. No other baseline details provided
Inclusion criteria: OSA and obstructive hyperventilation syndrome
Exclusion criteria: not reported
Interventions Bi-PAP versus fixed pressure CPAP
Outcomes 1. Symptoms (ESS)

2. Blood gases (PaO2 and PaCO2)
3. Lung function

terest statements
Notes Unpublished conference abstract
Risk of bias


(selection bias)

mance bias)

mance bias)
ment pressure

Informed decisions.
Gonzalez-Moro 2005 (Continued)


ment pressure

(attrition bias)
All outcomes

porting bias)
Gulati 2015
Methods Prospective, randomised, cross-over study in patients who were suboptimally compliant with CPAP de-
spite appropriate interventions. Data analysed as paired t test
Participants N = 28 participants (24 M/4 F). Mean Age 56.7 years; BMI 35 kg/m2; ESS 13.2; AHI 35
Inclusion criteria: OSA with AHI > 5, CPAP compliance < 4 hours per night for 6 weeks after CPAP pre-
scription despite technical and educational interventions, symptoms of pressure intolerance
Exclusion criteria: significant airflow obstruction (FEV1/FVC < 60%), pretreatment study showing cen-
tral sleep apnoea, clinical evidence of congestive heart failure, daytime hypercapnia (PaCO2 > 6.5kPa)
or previous prescription of Bi-PAP
Interventions Bi-PAP versus new CPAP (brand of fixed CPAP different from the one used prior to study entry)
Study duration: 2 x 4 weeks with 2 weeks washout in-between

2. Symptoms (ESS)
3. Maintenance of wakefulness test
4. Quality of life (SAQLI)
5. AHI
6. Device comfort
7. Preference
Funding & conflicts of in- Funding source: not declared; conflict of interest: none
terest statements
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Simple randomisation technique was used to allocate patients into
tion (selection bias) different groups."
Informed decisions.
Gulati 2015 (Continued)
Allocation concealment Low risk Quote: "(Allocation sequence concealment) was done independently by the
(selection bias) research and development officer, so the patients and researchers were not
aware of the allocation sequence."
Blinding of participants High risk Quote: "Neither (participants or research personnel) were blinded as the ma-
and personnel (perfor- chines used were different in each arm."
mance bias)
Blinding of participants Low risk Outcome assessors were not blinded to treatment allocation, but the out-
and personnel (perfor- comes unlikely to be affected by open-label design.
mance bias)
ment pressure
Blinding of outcome as- High risk Outcome assessors were not blinded to treatment allocation
Blinding of outcome as- Low risk Outcome assessors were not blinded to treatment allocation, but the out-
sessment (detection bias) comes unlikely to be affected by open-label design.
ment pressure
Incomplete outcome data Low risk Quote: "31 gave consent and were recruited. One developed a stroke during
(attrition bias) the treatment period (on Bi-level PAP arm) and 2 others did not complete the
All outcomes study (one of them dropped out after first using Bi-level PAP and the other af-
ter using the new CPAP). These subjects were excluded from the analyses."
Selective reporting (re- Low risk All outcomes were reported

porting bias)
Heiser 2010
Methods Randomised, parallel group study
Participants N = 74 participants (M/F 60/14). Mean age 58 years; BMI 31; AHI 35; ESS 9
Inclusion criteria: newly diagnosed OSA patients (AHI > 15 on polysomnography)
Interventions CPAP with warm air humidifier versus CPAP without warm air humidifier
Outcomes 1. Machine Usage (average hours used)

2. Symptoms (ESS)
3. Tolerability
4. Withdrawals
Informed decisions.
Heiser 2010 (Continued)
Funding & conflicts of in- Funding source: study was funded by manufacturers. Quote: "Diese Studie wurde finanziell unterstützt
terest statements durch die Firmen Fisher & Paykel Healthcare und Air Products Medical GmbH"
Author declaration of interests are identical to funding source
Notes
Risk of bias
Random sequence genera- Unclear risk Study participants assigned according to a randomised schedule but no more
tion (selection bias) detail provided about sequence of treatment group assignments
Allocation concealment Unclear risk No detail described. Insufficent information available to judge
(selection bias)
Blinding of participants Low risk Identical devices provided

mance bias)
Blinding of participants Low risk Identical devices provided

mance bias)
ment pressure
Blinding of outcome as- Low risk Identical devices provided

Blinding of outcome as- Low risk Identical devices provided

ment pressure
Incomplete outcome data High risk Non-users excluded from the analysis
(attrition bias)
All outcomes
Selective reporting (re- High risk Outcome data not available for symptoms. Objective of the study differed from
porting bias) that of the review question, but symptoms likely to have been collected.
Hudgel 2000
Methods Randomised, single-blind, cross-over study. Method of randomisation: hospital number (odd versus
even last digit)
Paired t test used for continuous data
Informed decisions.
Hudgel 2000 (Continued)
Participants N = 60 (53 with OSA and 7 with UARS). 21 withdrawals 2 stopped due to medical complications (not
stated) and the rest did not complete the study. Further 6 did not have machine usage data. (21 M/18
F). Total number of OSA patients completing trial is 29. Data analysed for 33 patients which included 4
patients with UARS
Mean age: 46 years; AHI 30; BMI: 42 kg/m2
Inclusion criteria: diagnosed OSA or UARS (confirmation by polysomnography)
Exclusion criteria: prior CPAP treatment, facial/pharyngeal abnormalities requiring surgery, chronic
airways disease necessitating bronchodilator usage, obesity hypoventilation syndrome, shift workers,
congestive heart failure, seizure disorder, mental retardation, sedative/antidepressant/hypnotic treat-
ment
Interventions Auto-CPAP versus fixed CPAP. No washout
Study duration: 2 x 12 week treatment periods
Outcomes 1. Treatment pressure

2. Symptoms (ESS)
3. Machine usage (hours of usage, % nights used effectively & % days used)
4. AHI

terest statements
Notes
Risk of bias
Random sequence genera- High risk Hospital number (odd versus even last digit)
Allocation concealment High risk Study investigators likely to be aware of treatment group assignment
(selection bias)
Blinding of participants High risk Study investigators likely to be aware of treatment group assignment
mance bias)
Blinding of participants Low risk These outcomes unlikely to be affected by study design
mance bias)
ment pressure
Blinding of outcome as- High risk Study investigators likely to be aware of treatment group assignment
Blinding of outcome as- Low risk These outcomes unlikely to be affected by open-label design
Informed decisions.
Hudgel 2000 (Continued)

ment pressure
Incomplete outcome data High risk High withdrawal rate and non-completers not included in analysis
(attrition bias)
All outcomes

porting bias)
Hukins 2004
Methods Randomised, single-blind, cross-over study. Method of randomisation: sealed envelopes (off-site)
Statistical analysis: paired t test
Participants N = 55 adults (48 M/7 F) randomised (46 completed). Age: 50 years; BMI: 35; AHI: 54; ESS: 12.5
Inclusion criteria: AHI ≥ 5; optimal treatment PSG determined optimal treatment pressure; no previ-
ous home use of CPAP
Exclusion criteria: significant comorbidity; complication (e.g. hypercapnic respiratory failure); non-
OSA; patients unable to use masks with Autoset T machines
Interventions Auto-CPAP (Autoset T) versus fixed pressure CPAP
Study duration: 2 x 8-week treatment periods
Outcomes 1. Symptoms (ESS)

2. Machine usage (average hours used)
4. Ease of use
5. Tolerability
Funding & conflicts of in- Quote: "This was an industry supported study by ResMed Australia. Dr. Hukins received research equip-
terest statements ment from ResMed Australia."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation was performed by a laboratory scientist not involved
tion (selection bias) with the study using the technique of shuffled sealed envelopes containing
equal numbers of each treatment arm"
Allocation concealment Low risk Quote: "Randomisation was performed by a laboratory scientist not involved
(selection bias) with the study using the technique of shuffled sealed envelopes containing
equal numbers of each treatment arm"
Informed decisions.
Hukins 2004 (Continued)
Blinding of participants High risk Quote: "....this single-blinded, randomised cross-over study.......The Autoset T
and personnel (perfor- was used for both treatment modes in an attempt to blind the patient to the
mance bias) mode...Investigators were not blinded..."
Blinding of participants Low risk These outcomes unlikely to be affected by single-blind study design.
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "Investigators were not blinded..."
Blinding of outcome as- Low risk These outcomes unlikely to be affected by open-label design.
ment pressure
Incomplete outcome data High risk Non-completers not included in analysis

(attrition bias)
All outcomes

porting bias)
Hussain 2004
Methods Randomised, single-blind, cross-over study. Method of randomisation not described. Statistical test:
paired t tests
Participants N = 10 (9 M/1 F). Mean age: 44.98; AHI: 47.2; BMI: 35.9; ESS: 11.1
Inclusion criteria: CPAP-naive at baseline; symptomatic OSA (AHI > 15/h)
Exclusion criteria: not described
Study duration: 2 x 4-week treatment periods (washout 2 weeks)

2. Symptoms (ESS)
3. AHI
5. Preference
6. Polsomnography outcomes
Informed decisions.
Hussain 2004 (Continued)
Funding & conflicts of in- Quote: "This study was funded by Respironics Inc., Murrysville, PA." Author conflicts of interest: not de-
terest statements clared
Notes
Risk of bias


(selection bias)
Blinding of participants High risk Quote: "...this randomized, prospective, single-blind cross-over trial.....Patients
and personnel (perfor- were unaware of the treatment mode..."
mance bias)
Blinding of participants Low risk These outcomes unlikely to be affected by single-blind study design.
mance bias)
ment pressure
Blinding of outcome as- High risk Study personnel would have been aware of treatment group assignment.
Blinding of outcome as- Low risk These outcomes unlikely to be affected by single-blind study design.
ment pressure

(attrition bias)
All outcomes

porting bias)
Jarvis 2006
Methods Randomised, cross-over study. Statistical analysis methods unclear but paired data obtained via corre-
spondence
Participants N = 20 participants
Inclusion criteria: diagnosed with OSA; established on CPAP therapy
Informed decisions.
Jarvis 2006 (Continued)
Interventions Modified APAP (bi-level pressure mode) versus fixed CPAP

2. AHI
4. Preference
Funding & conflicts of in- Resmed sponsored the study but no other details were available.
terest statements
Notes TJL emailed for confirmation of data and methods 5 September 2008. Reply from Resmed October 2008
Risk of bias
Random sequence genera- Low risk Quote: "The study was randomised by pulling the order of treatment received
tion (selection bias) 'out of a hat'"
Allocation concealment Low risk Quote: "The person who pulled the order was a ResMed employee indepen-
(selection bias) dent of the study and with no knowledge of the study."

mance bias)
mance bias)
ment pressure

ment pressure
Incomplete outcome data Low risk All completed

(attrition bias)
All outcomes

porting bias)
Informed decisions.
Kendrick 2002
Methods Randomised, double-blind, cross-over study
Participants N = 41 (38M/3F). 27 completed the study. Mean age: 52.4 years; BMI: 32.3kg/m2; ESS 13.9
Eligibility criteria not provided
Outcomes 1. Machine usage

2. Sympotoms (ESS)
3. AHI
4. Mean pressure for treatment

terest statements
Notes
Risk of bias


(selection bias)

mance bias)

mance bias)
ment pressure


ment pressure
Informed decisions.
Kendrick 2002 (Continued)

(attrition bias)
All outcomes

porting bias)
Konermann 1998
Methods Randomised, single-blind, parallel group study. Method of randomisation not reported
Participants N = 50 participants (44 M/6F); Age 53.5. No other baseline details available
Study duration: 3 to 6 weeks
Outcomes 1. Machine usage (average hours used and week with CPAP use > 4 hours)
3. Polysomnography (% sleep efficiency; % time awake; % sleep stage 1 and 2; % sleep stage 3 and 4
4. AHI
5. Withdrawals

terest statements
Notes Sleep study following treatment done between 3 and 6 months
Risk of bias
Random sequence genera- Unclear risk Quote: "Patients were randomly assigned to receive either automatically ad-
tion (selection bias) justing or conventional nCPAP."

(selection bias)
Blinding of participants High risk Quote: "the design of the study was single-blinded"
mance bias)
mance bias)
ment pressure
Informed decisions.
Konermann 1998 (Continued)
Blinding of outcome as- High risk Quote: "the design of the study was single-blinded"
ment pressure
Incomplete outcome data High risk Non-completers did not contribute to the analysis (4%)
(attrition bias)
All outcomes

porting bias)
Kushida 2011
Methods A prospective, randomised, double-blinded, three-arm, multicenter trial
Participants N = 168 participants (128 M/40 F). Age: 49 years; BMI: 34 kg/m2; AHI: 39; ESS: 11
Inclusion criteria: age 21-75 years, AHI > 15/hour, able to consent, agreeable to commence CPAP as ini-
tial therapy, adequate titration within 2 weeks of enrolment
Exclusion criteria: previous study participation < 30 days, > 1 titration, sedatives, medical/psychiatric
illness potentially interfering with CPAP adherence, CPAP exposure < 1 year, chronic respiratory dis-
ease, upper airway surgery < 90 days, previous surgery for OSA, non-OSA sleep disorder, excess alcohol
use, shift workers
Interventions Comparing effects of autoadjusting PAP EXPssure relief with autoadjusting PAP and fixed CPAP
Study duration: 6 months (see notes)

2. AHI
3. Symptoms (ESS)
4. Blood pressure
6. Withdrawals
7. Patient preference
8. Treatment satisfaction
10.Adverse events
Funding & conflicts of in- Quote: "Philips Respironics provided funding for this study; Drs. Kushida, Berry, Blau, Fietze, Kryger,
terest statements Kuna, Pegram, and Penzel received research support for the conduct of this study through contracts
between Philips Respironics and their respective institutions. Ms. Crabtree received consulting fees
for statistical data analysis from Philips Respironics. Dr. Kushida has received research support from
Philips Respironics, ResMed, Ventus Medical, and Pacific Medico. Dr. Berry has received research sup-
port from Philips Respironics, ResMed, and Ventus Medical. Dr. Blau has received research support
from Philips Respironics, Breas, and Hoffrichter) Dr. Fietze has received research support from Philips
Informed decisions.
Kushida 2011 (Continued)

Respironics, ResMed, Advanced Sleep Research, Breas, Hoffrichter, and Weinmann. Dr. Kryger has
received research support from Ventus, and ResMed. Dr. Penzel has received research support from
Philips Respironics, ResMed, Advanced Sleep Research, Breas, Hoffrichter, Somnomedics, and Wein-
mann."
Notes Patients in APAP group - initially APAP for two weeks followed by fixed CPAP for six months
Risk of bias
Random sequence genera- Low risk Quote: "Urn randomization was used to control for the potentially confound-
tion (selection bias) ing variables (age, gender, education, AHI, subjective sleepiness)"
Allocation concealment Unclear risk Insufficient information to make judgement

(selection bias)
Blinding of participants Low risk Quote: "The Principal Investigator (PI) and research staff administering ques-
and personnel (perfor- tionnaires or interacting with the participant were blinded to randomization
mance bias) and the results of all participant evaluations...participants were blinded to
Machine usage, symp- treatment"
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "The Principal Investigator (PI) and research staff administering ques-
sessment (detection bias) tionnaires or interacting with the participant were blinded to randomization
Machine usage, symp- and the results of all participant evaluations"
ment pressure
Incomplete outcome data Low risk Quote: "Fourteen participants did not receive the therapy to which they were
(attrition bias) randomized, but were included in the intention-to-treat analysis."
All outcomes

porting bias)
Leidag 2008
Methods Randomised, double-blind, cross-over trial
Participants N = 30 participants (22 M/8 F). Age: 55.4 years, BMI 32
Inclusion criteria: clinical suspicion of OSAS with AHI > 5 on polysomnography

Informed decisions.
Leidag 2008 (Continued)

Exclusion criteria: severe comorbidity, such as acute or chronic heart failure (NYHA grade 3 or 4), se-
vere COPD, dementia, alcoholism, drug abuse, and age under 18
Interventions CPAP versus C-Flex

2. Leakage
3. Withdrawals
4. AHI
Funding & conflicts of in- Funding quote: "This study was supported by Air Products Medical GmbH."
terest statements Conflicts of interest quote: "The authors had no conflicts of interest to declare in relation to this arti-
cle."
Notes
Risk of bias
Random sequence genera- Unclear risk Insufficient information to make judgement

Allocation concealment Unclear risk Insufficient information to make judgement

(selection bias)
Blinding of participants Low risk Quote: "The physicians and technicians performing the titration and scoring
and personnel (perfor- the polysomnographic data were blinded to the treatment mode which was
mance bias) chosen...The patients were only informed that they would receive two differ-
Machine usage, symp- ent modes of therapy, but they did not know if they got CPAP or C-Flex"
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "The physicians and technicians performing the titration and scoring
sessment (detection bias) the polysomnographic data were blinded to the treatment mode which was
Machine usage, symp- chosen"
ment pressure
Incomplete outcome data Low risk Quote: "Twelve patients dropped out of the study (7 after C-Flex, 5 after CPAP);
(attrition bias) 4 of them gave up the therapy completely (2 after CPAP, 2 after C-Flex)"
All outcomes
Informed decisions.
Leidag 2008 (Continued)

porting bias)
Loube 2004
Methods Randomised study. Design and method of randomisation not reported. Single-blind trial
Participants N = 16 participants. Distribution and baseline details not reported
Inclusion criteria: participants with newly diagnosed CPAP; AHI > 15; uncomplicated CPAP lab PSG
Exclusion criteria: REM-related/supine positional OSA
Interventions C-Flex PAP versus fixed pressure CPAP

2. Symptoms (ESS)

terest statements
Notes Unpublished conference abstract. Details requested by email
Risk of bias

Allocation concealment Unclear risk Information not available; requested

(selection bias)

mance bias)

mance bias)
ment pressure

Informed decisions.
Loube 2004 (Continued)

ment pressure
Incomplete outcome data Unclear risk Information not available; requested

(attrition bias)
All outcomes

porting bias)
Marrone 2004
Methods Randomised, single-blind, cross-over study. Method of randomisation: not described. Statistical analy-
sis: unpaired t test
Participants N = 22 participants (21 M/1 F). Mean age 53.45; BMI: 32.9; ESS: 16.3
Inclusion criteria: newly diagnosed OSA; AHI ≥ 30
Exclusion criteria: not described
Study duration: 2 x 4 weeks. No washout described
Outcomes 1. Machine usage (average hours used, nights used effectively & frequency of use as % days))
2. Symptoms (ESS)
4. Preference
Funding & conflicts of in- Funding quote: "This study was supported by Air Products Medical GmbH."
terest statements Conflicts of interest quote: "The authors had no conflicts of interest to declare in relation to this arti-
cle."
Notes —
Risk of bias
Random sequence genera- Unclear risk Quote: "Machines were assigned in a single blind, random fashion."
Allocation concealment High risk Given that the study was single-blind, the pressure setting of the machines
(selection bias) may have been known by investigators
Blinding of participants High risk Single-blind study

mance bias)
Informed decisions.
Marrone 2004 (Continued)

mance bias)
ment pressure
Blinding of outcome as- High risk Single-blind study

ment pressure
Incomplete outcome data Low risk All participants completed the study
(attrition bias)
All outcomes
Selective reporting (re- Unclear risk No information available

porting bias)
Marshall 2008
Methods Randomised, single-blind, parallel group trial
Participants N = 19 participants (15 M/4 F). Mean age: 47; AHI: 78; ESS: 14
Inclusion criteria: severe OSA (AHI > 30; or symptomatic and AHI > 20)
Exclusion criteria: other significant medical disorders
Interventions C-Flex versus fixed CPAP

2. Symptoms (ESS)
Funding & conflicts of in- Quote: "None of the authors have had any financial relationships with Respironics Inc., who are the
terest statements manufacturers of the device tested. Respironics International Inc., through their New Zealand suppliers
Care Medical, provided six C-Flex machines for the purposes of this trial."
Notes Information on randomisation available from study authors
Risk of bias
Informed decisions.
Marshall 2008 (Continued)
Random sequence genera- Low risk Quote: "The sequence of allocation to treatment was determined by sleep
tion (selection bias) technicians randomly picking one of a set of pre-prepared opaque envelopes
containing the treatment allocation."
Allocation concealment Low risk Quote: "An urn with 2 differently coloured paper clips was prepared. One clip
(selection bias) was blindly withdrawn, and its corresponding treatment noted on a folded
piece of paper in an opaque envelope which was then sealed. The clip was
then replaced in the urn along with another coloured clip, which represented
the other treatment. This was repeated until 20 envelopes had been produced.
Because a number of patients who did not meet the entry requirements, were
randomised and then withdrawn from the study, a further 5 envelopes were
subsequently prepared using the same method. This method leads toward
roughly equal group sizes whilst maintaining unpredictability of sequence and
sample sizes."
Blinding of participants High risk Study personnel would have been aware of treatment group allocation.
mance bias)
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "Measurements of sleepiness and reaction times were undertaken by
sessment (detection bias) an investigator blinded to treatment allocation; patients were blinded to treat-
Machine usage, symp- ment allocation."
Blinding of outcome as- Low risk These outcomes unlikely to be affected by awareness of treatment group allo-
sessment (detection bias) cation
ment pressure
Incomplete outcome data Low risk Quote: "Whilst all 19 patients were included in the primary analysis under the
(attrition bias) intention-to-treat principle due to missed appointments only 17 patients are
All outcomes included in the Epworth analysis." This is a low rate of attrition.

porting bias)
Masa 2015
Methods Randomised, three-arm, parallel group
Participants N = 151 participants entered into treatment groups relevant to this review question (66 M/85 F); age: 60
years; BMI: 44; AHI: 69; ESS: 11
Inclusion criteria: 15-80 years; AHI: > 30; no other significant sleep disorders (e.g. narcolepsy or rest-
less leg syndrome); correctly executed 30-minute CPAP/NIV test
Informed decisions.
Masa 2015 (Continued)

Exclusion criteria: significant comorbidity
Interventions Fixed CPAP versus Non-invasive ventilation treatment set at bilevel pressure with assured volume.
Study assigned to bi-level PAP comparison. Supplemental oxygen offered if participants met additional
criteria (daytime PaO2 < 55 mmHg, with the necessary flow to maintain waking arterial oxygen satura-
tion between 88% and 92% or PaO2 greater than or equal to 55 mmHg for at least 17 h/d).
Third treatment arm consisting of a usual care control was not of interest to this review.
Study duration: 3 years (for hospitalisation and withdrawal outcomes). Other outcome data reported at
8 weeks unless stated.

2. Blood gas (PaCO2 at 3 months)
3. Cardiovascular markers (HbA1C, Lipid profile)
5. Symptoms (ESS)
6. Nocturnal oximetry
7. AHI
8. Adverse events
Funding & conflicts of in- Quote: "Supported by the Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio
terest statements de Sanidad y Consumo) grant PI050402, the Spanish Respiratory Foundation 2005 (FEPAR), and Air Liq-
uide Spain."
Funders did not participate in the design or conduct of the study, analysis or interpretation of data, or
manuscript preparation.
The authors all declared that they had no conflicts of interest.
Notes
Risk of bias
Random sequence genera- Low risk Quote: participants "randomized by an electronic database (simple random-
tion (selection bias) ization)."
Allocation concealment Unclear risk Insufficient information available to judge.

(selection bias)
Blinding of participants High risk For most outcomes of interest to the review open-label nature of the study
and personnel (perfor- places the study at high risk of performance bias.
mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk For most outcomes of interest to the review open-label nature of the study
sessment (detection bias) places the study at high risk of detection bias.
Informed decisions.
Masa 2015 (Continued)

ment pressure
Incomplete outcome data Unclear risk 10% of participants missing data at 2 months. ITT was undertaken with miss-
(attrition bias) ing data imputed for secondary outcomes (quote): "following a multiple impu-
All outcomes tation method with iterative multivariable regression, because the missing da-
ta had characteristics compatible with a missing at random pattern."
Selective reporting (re- Low risk Outcomes of interest reported in accordance with trial registry record.
porting bias)
Other bias Low risk No other sources of bias identified.
Massie 2003
Methods Randomised, single-blind, cross-over study. Methods of randomisation not reported. Comparisons be-
tween treatment using 2-way analysis of variance - treatment order as between-subject factor, and
treatment type within-subject factor
Participants N = 46 participants (36 M/10 F) 1 dropout and 1 data unavailable from machine. Mean age: 49; BMI:
32kg/m2
Inclusion criteria: 18 to 65 years; symptomatic OSA; AHI > 15; > 10 cmH2O to correct AHI
Exclusion criteria: pre-existing lung disease; awake resting SaO2 < 90%; 10 or more central ap-
noeas/hr; patients taking medication considered to interfere with sleep respiration
Outcomes 1. Machine usage (average hours used and % days used)

3. AHI
4. Quality of life (SF-36 score reported by domain)
5. Symptoms (ESS and sleep diary score)
Funding & conflicts of in- Supported by a grant from ResMed Corporation. One of the authors (Neil Douglas) declared a role as
terest statements medical advisor to ResMed
Notes Participants aware that machine usage was monitored; stipend offered for completion of study
Risk of bias

Informed decisions.
Massie 2003 (Continued)

(selection bias)
Blinding of participants High risk Quote: ".....randomised, single-blinded, cross-over study....(patients) were not
and personnel (perfor- informed of the type of therapy they were receiving"
mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk Single blind study

ment pressure
Incomplete outcome data Low risk Low rate of non-completers excluded. One excluded from study and additional
(attrition bias) participant excluded from analysis of machine usage due to unreadable data.
All outcomes
Selective reporting (re- Unclear risk All outcomes reported

porting bias)
Meurice 1996
Methods Randomised, parallel group study. Statistical analysis based on t tests but unadjusted data presented
for all outcomes.
Participants N = 16 participants (16 M). Mean age: 54; BMI: 34.2 kg/m2; AHI: 43.6; ESS: 14.8
Inclusion criteria: diagnosis of OSA (confirmed by polysomnography; untreated OSA)

2. AHI
3. Symptoms (ESS)
4. Withdrawals
Informed decisions.
Meurice 1996 (Continued)

terest statements
Notes
Risk of bias
Random sequence genera- Low risk Random numbers table


(selection bias)
Blinding of participants Low risk Participants unaware as to group they were randomised to (CPAP machines
and personnel (perfor- were identical).
mance bias)
mance bias)
ment pressure
Blinding of outcome as- Low risk Participants unaware as to group they were randomised to (CPAP machines
sessment (detection bias) were identical).
ment pressure
(attrition bias)
All outcomes

porting bias)
Meurice 2007
Methods Randomised, multicentre, parallel group trial
Participants N = 83. Mean age: 56 years; AHI: 52; ESS: 11.5
Inclusion criteria: new diagnosis of OSA; CPAP-naive; AHI > 30
Informed decisions.
Interventions Four auto-CPAP machines assessed:
1. GK 418 P, 3.1 version

2. AutoSet Spirit, 302 version
3. PV 10I, firmware 0.92 version
4. Somnosmart 1, 2.02 version
All 4 compared against fixed pressure CPAP

2. AHI
3. Symptoms (ESS)
4. Withdrawals

terest statements
Notes Data aggregated from 4 auto-CPAP groups
Risk of bias
Random sequence genera- Unclear risk Quote: "The randomisation was carried out centrally..."
Allocation concealment Low risk Quote: "...randomly coded envelopes opened by a coordinator from envelopes
(selection bias) batched for each centre in order to have similar proportions of patients in each
group from each centre."

mance bias)
mance bias)
ment pressure

ment pressure
Informed decisions.
Incomplete outcome data High risk Participants who withdrew were not included in the analysis
(attrition bias)
All outcomes

porting bias)
Meurice 2009
Methods Randomised, single-blind, cross-over trial. Statistical methods unclear
Participants N = 20. Age 57 years
Interventions Automatic-CPAP device combined with pressure reduction during exhalation (auto C-Flex) versus fixed
CPAP
Study duration: 2 x 1 month

3. AHI
4. Quality of Life (FOSQ)
5. Epworth Sleepiness Scale
6. Preference

terest statements
Notes
Risk of bias
Random sequence genera- Unclear risk No information available

Allocation concealment Unclear risk No information available

(selection bias)
Blinding of participants High risk Single-blinded study

mance bias)
Blinding of participants Unclear risk No information available

mance bias)
ment pressure
Informed decisions.
Blinding of outcome as- High risk Single-blinded study

Blinding of outcome as- Unclear risk No information available

ment pressure
Incomplete outcome data Unclear risk No information available

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk No information available. Information only available as a conference abstract.
porting bias) No further details about the study are available.
Other bias Unclear risk No information available
Modrak 2007
Methods Randomised, cross-over study. Statistical analysis unclear
Participants N = 26 participants. Baseline details not available
Inclusion criteria: diagnosis of OSA; CPAP-naive
Interventions CPAP + expiratory pressure relief versus fixed CPAP

terest statements
Notes —
Risk of bias


(selection bias)
Blinding of participants High risk Quote: "A randomized two-arm prospective crossover unblinded....."
mance bias)
Informed decisions.
Modrak 2007 (Continued)

mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "A randomized two-arm prospective crossover unblinded....."

ment pressure

(attrition bias)
All outcomes

porting bias)
Muir 1998
Methods Randomised, double-blind, cross-over study. Method of randomisation not reported. Statisitical analy-
sis unclear
Participants N = 16 participants. Mean age: 59 years; BMI: 31 kg/m2; AHI: 69
Inclusion criteria: previously documented OSA and poor compliance with CPAP (< 3 hours/night)
Interventions Bi-level PAP versus fixed CPAP
Pressure levels for inspiratory pressure were: 12.3 cmH2O (SD 1.8), and expiratory pressure: 7.6 cmH2O
(SD 2.2) for bilevel PAP treatment, and for fixed CPAP: 9.4 cmH2O (SD 2.3) (no P value reported)

2. Adverse events
3. Preference

terest statements
Notes Study published as conference abstract
Risk of bias
Informed decisions.
Muir 1998 (Continued)


(selection bias)
Blinding of participants Unclear risk Quote: "Double-blind, crossover study". No further information available.
mance bias)
Blinding of participants Unclear risk We have judged the risk of bias on objective outcomes to be unclear in the ab-
and personnel (perfor- sence of more detail beyond the study being double-blind.
mance bias)
ment pressure
Blinding of outcome as- Unclear risk Quote: "Double-blind, crossover study". No further information available.
Blinding of outcome as- Unclear risk We have judged the risk of bias on objective outcomes to be unclear in the ab-
sessment (detection bias) sence of more detail beyond the study being double-blind.
ment pressure

(attrition bias)
All outcomes

porting bias)
Neill 2003
Methods Randomised, double-blind, cross-over study. Method of randomisation not reported. Statisical test: not
reported although exact P values presented for between group tests and confidence interval reported
for machine usage.
Participants N = 42 randomised (37 completed study protocol and were analysed). Mean age: 49 years. BMI: 35 kg/
m2; RDI: 50; ESS: 12.1
Inclusion criteria: newly diagnosed OSA requiring treatment with CPAP
Exclusion criteria: significant nasal obstruction; requirement for supplemental oxygen
Interventions Humidification in addition to nasal CPAP versus sham humidifier in addition to nasal CPAP
Study duration: 2 x 3-week treatment periods (3 day washout)

Informed decisions.
Neill 2003 (Continued)

2. ESS
3. Upper airway symptoms
4. Preference
Funding & conflicts of in- Quote: "This study was funded by an Otago University Research Grant."
terest statements
Author declarations not provided (conference abstract)
Notes
Risk of bias


(selection bias)
Blinding of participants Low risk Quote: "The authors attempted to create a placebo humidification arm in
and personnel (perfor- which the HC100 was used without the heating unit turned on.........An inves-
mance bias) tigator blinded to research treatment interviewed the patients at the end of
Machine usage, symp- each treatment arm..."
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "An investigator blinded to research treatment interviewed the patients
sessment (detection bias) at the end of each treatment arm..."
ment pressure
Incomplete outcome data High risk Non-completers excluded from analysis

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk Not possible to determine based on details provided
porting bias)
Nilius 2006
Methods Randomised, parallel group trial
Informed decisions.
Nilius 2006 (Continued)
Participants N = 51 participants; mean age: 57 years; AHI: 53.3
Inclusion criteria: AHI > 20
Exclusion criteria: Inability to follow instructions, failure to give informed consent, acute infection,
acute cardiac disease such as acute coronary artery syndrome, NYHA grade 3 or 4 heart failure, and
acute pulmonary thromboembolism
Interventions CPAP with expiratory pressure relief versus fixed CPAP

2. AHI
3. Symptoms (ESS)
Funding & conflicts of in- Quote: "This study was financed by a gift from Heinen U. Lowenstein. Dr. Ruhle has received research
terest statements funding from Fisher A. Paykel, Heinen U. Lowenstein, ResMed, and Weinmann, but this funding has
gone into department funds. Dr. Nilius, Andreas Happel, and Ulrike Domanski have reported to the AC-
CP that no significant conflicts of interest exist with any companies/organizations whose products or
services may be discussed in this article."
Notes
Risk of bias

Allocation concealment Low risk Third party responsible for randomisation and setting machines to relevant
(selection bias) treatment mode
Blinding of participants Low risk Quote: "The patients were informed that they would receive two different
and personnel (perfor- forms of treatment .....but were given no further details...........The technician
mance bias) had no information from the investigators about the modality that the pa-
Machine usage, symp- tients were receiving"
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "The physician and technicians reviewing the polysomnographic da-
sessment (detection bias) ta and performing the manual CPAP titration were blinded to the treatment
Machine usage, symp- mode employed"
ment pressure
Informed decisions.
Nilius 2006 (Continued)
Incomplete outcome data Low risk All participants accounted for in analysis
(attrition bias)
All outcomes

porting bias)
Nolan 2007
Methods Randomised, single-blind, cross-over study. Statistical test: Wilcoxon matched pair test
Participants N = 34 participants (completed: 29 (26 M/3 F)). Mean age: 53 years; BMI: 29.9 kg/m2; AHI: 14.7; ESS: 12.3
Inclusion criteria: mild to moderate OSA (AHI 5-30)
Interventions Auto-CPAP versus fixed pressure CPAP
Outcomes 1. Machine usage (average hours used and % days used)

2. Symptoms (ESS)
3. AHI
4. Preference
Funding & conflicts of in- Quote: "This was not an industry supported study. Drs. Nolan, Doherty, and Mc Nicholas have indicated
terest statements no financial conflicts of interest."
Notes
Risk of bias

Allocation concealment Low risk Quote: "An independent person not involved in the study design, protocol, or
(selection bias) analysis assigned the devices to the patients in random order."
Blinding of participants Low risk Quote: "....patients were not informed about the different technologies used
and personnel (perfor- in the devices.....the trial was fully blinded to the investigator performing the
mance bias) analysis."
mance bias)
ment pressure
Informed decisions.
Nolan 2007 (Continued)
Blinding of outcome as- Low risk Quote: "...the trial was fully blinded to the investigator performing the analy-
sessment (detection bias) sis."
ment pressure
Incomplete outcome data High risk High rate of participants not crossing over on to subsequent treatment arm
(attrition bias)
All outcomes

porting bias)
Noseda 2004
Methods Randomised, single-blind, cross-over study. Method of randomisation: random numbers table.
Statistical analysis: student's t test (paired data)
Participants N = 27 participants (23 M/4 F). Withdrawals: 3. Total completed and analysed N = 24. Mean age: 49
years; BMI: 32.3 kg/m2; AHI: 50.9; ESS 10.7
Inclusion criteria: AHI > 20/hour; MAI: > 30/hour; high variability of within night pressure to correct AHI
Exclusion criteria: prior treatment with CPAP; central OSA/Cheyne Stokes; major facial abnormali-
ty; night/shift work; severe chronic heart failure/COPD; seizure disorder; mental retardation; sedative,
hypnotic or antidepressant therapy; previous UPPP; prolonged hypoventilation during REM
Interventions Auto-CPAP versus fixed CPAP. Need for pressure assessed over a 14-night run-in period with auto-CPAP.
No washout period described
Outcomes 1. Machine usage (nights used effectively)

2. Symptoms (ESS)
3. Preference
5. Self-estimated sleep latency

terest statements
Notes
Risk of bias
Informed decisions.
Noseda 2004 (Continued)
Random sequence genera- Low risk Randomisation tables


(selection bias)
Blinding of participants High risk Quote: ".....single-blind, randomized, crossover trial........subjects were
and personnel (perfor- told that they would sleep with the machine functioning in two distinct
mance bias) modes.....no further explanation was given."
mance bias)
ment pressure
Blinding of outcome as- High risk Single-blind nature of the study means that these outcomes are at risk of bias
ment pressure
Incomplete outcome data High risk Rate of participants not crossing over could be high enough to introduce bias
(attrition bias)
All outcomes

porting bias)
Nussbaumer 2006
Methods Randomised, cross-over study. Double-blinding: investigators and participants unaware as to treat-
ment. Same machine used to deliver both treatment pressure modalities. Identical chip card given to
patient which contains algorithm for either fixed or automatic titration mode.
Statistical test: paired t test
Participants N = 38 participants (30 completed the study and contributed to the analysis) (27 M/3 F). Mean age: 49
years; BMI: 31 kg/m2; ESS: 12.7; AHI: 41.1
Inclusion criteria: AHI > 10 events/hour
Exclusion criteria: CHF; chronic rhinitis; other sleep disorders
No washout period described
Informed decisions.
Nussbaumer 2006 (Continued)

Outcomes 1. Machine usage (average hours used and % nights used > 4 hours)
2. Symptoms (ESS)
3. AHI
6. Preference
Funding & conflicts of in- Quote: "Study supported by MADELA AG, distributors of Respironics products in Switzerland".
terest statements
No author conflicts provided.
Notes —
Risk of bias
Random sequence genera- Unclear risk Treatments given in "random order"


(selection bias)
Blinding of participants Low risk Quote: "Patients and attending physicians were blinded to treatment modes
and personnel (perfor- and order of application."
mance bias)
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "attending physicians were blinded to treatment modes and order of
sessment (detection bias) application."
ment pressure
Incomplete outcome data High risk Non-completers excluded from the analysis (N = 8)
(attrition bias)
All outcomes

porting bias)
Informed decisions.
Patruno 2007
Participants N = 31 participants (25 M/ 6 F). Mean age: 48 years; BMI: 36.5kg/m2; AHI: 47; ESS: 15
Inclusion criteria: AHI > 20; ESS > 12
Exclusion criteria: not specified

2. AHI
3. Symptoms (ESS)
4. Blood pressure
Funding & conflicts of in- Quote: "This work was supported by a University of Milan Fondo Interuniversitario per la Ricerca Scien-
terest statements fifica e Technologia Grant and a Minister for Instruction, University and Research Progetto di Ricerca
di Interesse Nazionale 2003 grant to Dr. Montano. The authors have no financial or other potential con-
flicts of interest to disclose."
Notes
Risk of bias
Random sequence genera- Unclear risk Quote: "After CPAP titration, all subjects were randomised to receive either
tion (selection bias) fixed-level CPAP for 3 months."

(selection bias)

mance bias)
mance bias)
ment pressure

Informed decisions.
Patruno 2007 (Continued)

ment pressure
Incomplete outcome data High risk 40 participants recruited; 9 withdrew (no information on which groups they
(attrition bias) were assigned to); 3 of these participants withdrew due to poor compliance
All outcomes
Selective reporting (re- High risk Data on ESS not presented: requested from authors along with details of ran-
porting bias) domisation and withdrawals
Powell 2012
Methods Parallel group, randomized, double-blind, controlled study
Participants N = 48 participants (37 M/9 F). Age: 55 years; BMI: 33 kg/m2; ESS: 9
Inclusion criteria: 21 to 75 years; AHI > 15; suboptimal CPAP titration after at least 3 hours of attempt-
ed titration
Exclusion criteria: major medical or psychiatric illness; chronic respiratory failure; upper airway/ENT
surgery in last 90 days; shift workers; alcohol/drug abuse within last three years; hypnotic use < 3
months; PLMI > 10 per hour; complex/central sleep apnoea; CPAP contraindication
Interventions Auto bi-PAP (nasal) versus fixed CPAP
Study duration: 90 days
Outcomes 1. Machine usage (average hours used and N using it effectively)

2. Symptoms (ESS and Fatigue Severity Scale)
4. Withdrawals
Funding & conflicts of in- Quote: "This study was supported by a grant from Phillips Respironics. Dr. Powell has received research
terest statements support from Philips Respironics, Inc, Fisher – Paykel Healthcare, and Takeda Pharmaceuticals Dr. Mal-
hotra has received consulting and/or research support from NIH, AHA, Philips, Medtronic, Apnex, SHC,
SGS, Apnicure, Galleon, Pfizer, Merck, Cephalon, and Sepracor. Dr. Litinski has received research sup-
port from the American Sleep Medicine Foundation. Dr. Gay has received research support from Philips
Respironics, Inc. Dr. Ojile has indicated no financial conflicts of interest."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Urn randomization was used for treatment group placement using the
tion (selection bias) variables of gender, age, diagnostic AHI, and education"
Allocation concealment Low risk Quote: "Urn randomization was used for treatment group placement using the
(selection bias) variables of gender, age, diagnostic AHI, and education"
Blinding of participants Low risk Quote: "The participant, investigator, respiratory therapist, and research staff
and personnel (perfor- were all blinded to the therapy group"
mance bias)
Informed decisions.
Powell 2012 (Continued)

mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "The participant, investigator, respiratory therapist, and research staff
sessment (detection bias) were all blinded to the therapy group"
ment pressure
Incomplete outcome data Low risk Quote: "A total of 48 participants were randomized into the trial......A total of
(attrition bias) 48 participants were analyzed for the primary endpoint on an intent-to-treat
All outcomes basis"
Selective reporting (re- High risk Study protocol indicates that AHI was measured but this was not reported in
porting bias) main trial publication.
Pépin 2009
Methods Multicentre, randomised, controlled, double-blind trial
Participants N = 218 (172 M/46 F). Age: 55 years; BMI: 31 kg/m2; AHI: 44; ESS: 11.5
Inclusion criteria: newly diagnosed sleep apnoea patients over 18 years of age who were referred for
CPAP
Exclusion criteria: pregnancy, medically unstable, predominantly central sleep apnoea
Interventions Comparing effect of C-Flex versus fixed CPAP
Outcomes 1. Machine use (average hours used)

2. Quality of life (SF-36 and Grenoble SAQOL)
3. Tolerability
4. Withdrawals
5. Symptoms (ESS)
Funding & conflicts of in- Quote: "This work was supported by grants from 'Comite ́ National des Maladies Respiratoires' and
terest statements Respironics. Author conflicts not reported."
Notes
Informed decisions.
Pépin 2009 (Continued)
Risk of bias
Random sequence genera- Low risk 'Randomization was performed by a computer-generated schedule in random
tion (selection bias) blocks of six and was stratified according to study centers'
Allocation concealment Low risk 'Randomization was performed by a computer-generated schedule in random
(selection bias) blocks of six and was stratified according to study centers'
Blinding of participants Low risk 'Patients were not aware of whether they were receiving CPAP with or without
and personnel (perfor- C-Flex activated'.........'The investigators who assessed outcome were unaware
mance bias) of the randomization status of the patients'
mance bias)
ment pressure
Blinding of outcome as- Low risk 'The investigators who assessed outcome were unaware of the randomization
sessment (detection bias) status of the patients and did not set up or maintain the machines'
ment pressure
Incomplete outcome data High risk 'The data for all outcomes were analyzed on an intention-to treat basis'. Bal-
(attrition bias) anced but high rates of withdrawal. Reasons for withdrawal include refusal to
All outcomes continue with treatment

porting bias)
Pépin 2016
Methods Single-centre, randomised controlled, double-blind, parallel group trial
Participants N = 322 participants (225 M/97 F). Age: 58; BMI: 30 kg/m2 AHI: 38.8
Inclusion criteria: age: 18 to 80 years, capable of providing written informed consent, patients claim-
ing social insurance and patients with OSA needing CPAP treatment
Exclusion criteria: cardiac failure known and treated, central apnoea syndrome, patients who stopped
CPAP treatment in the previous year, pregnancy, patients under guardianship, imprisoned patients, pa-
tients in hospital, patients included in another clinical study
Informed decisions.
Interventions Fixed versus auto-CPAP
Outcomes 1. Machine usage (average hours used and N using > 4 hours per night)
2. Symptoms
3. Blood pressure
4. Withdrawals
Funding & conflicts of in- Quote: "The study was funded by the Fondation Agir pour les maladies chroniques. The corresponding
terest statements author had full access to all the data in the study and had final responsibility for the decision to submit
for publication."
Author conflicts of interest: none declared
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation was conducted by...a computer-generated random
tion (selection bias) numbers list (six patients per block)."
Allocation concealment Low risk Quote: "Randomisation was conducted by telephone call to a clinical trials sta-
(selection bias) tistician, independent of the study..."
Blinding of participants Low risk Quote: "All patients, investigators and outcome assessment technicians were
and personnel (perfor- blinded to the arms to which the patients were allocated."
mance bias)
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "All patients, investigators and outcome assessment technicians were
sessment (detection bias) blinded to the arms to which the patients were allocated."
ment pressure
Incomplete outcome data High risk High and imbalanced rate of withdrawal between intervention groups. Multi-
(attrition bias) plie imputation method used to replace missing values from ITT analysis.
All outcomes
Informed decisions.
Selective reporting (re- High risk Quality of life, as measured by SF-36 was described as not different between
porting bias) the two arms. The trial registry record indicated that symptoms was also mea-
sured but this was not reported in the trial publication.
Randerath 2001
Methods Randomised, cross-over study. ANOVA test with Bonferroni correction used (for differences between
baseline and treatment mode, and for differences between treatment mode)
Participants N = 52 participants (45 M/7 F). Mean age: 54.7 years; BMI: 32.4 kg/m2; AHI 35.1
Inclusion criteria: confirmed OSA by polysomnography
Exclusion criteria: prior treatment with CPAP
Interventions Auto-CPAP versus fixed CPAP. No washout
24-hour telephone helpline was at the disposal of the participants

2. AHI
3. Arousals
5. Preference
Funding & conflicts of in- Quote: "The devices were supplied by the Weinmann Company, Hamburg, Germany." No author con-
terest statements flicts provided
Notes
Risk of bias

Allocation concealment Low risk Quote: "Only the person who managed the randomisation knew about the or-
(selection bias) der of the treatment modes in the individual patients. This person adjusted
the devices to the different treatment modes."
Blinding of participants Low risk Quote: "Those who did the questioning and cared for the patients in the hospi-
and personnel (perfor- tal and sleep laboratory and those who evaluated results of PSG were blinded
mance bias) to the mode of treatment applied.........The patients were not informed about
Machine usage, symp- the sequence in which the two treatment modes were applied."
mance bias)
Informed decisions.
Randerath 2001 (Continued)

ment pressure
Blinding of outcome as- Low risk Quote: "Those who did the questioning and cared for the patients in the hospi-
sessment (detection bias) tal and sleep laboratory and those who evaluated results of PSG were blinded
Machine usage, symp- to the mode of treatment applied."
ment pressure
Incomplete outcome data High risk 5/52 participants withdrew; their data were excluded from analysis
(attrition bias)
All outcomes

porting bias)
Reeves-Hoché 1995
Participants N = 83 (gender available for 62 completers: 45 M/17 F). Mean age: 47; BMI: 40 kg/m2; AHI: 51
Inclusion criteria: OSA diagnosed according to American Sleep Disorders Association AHI > 10; "heavy
snoring"; excessive daytime sleepiness
Exclusion criteria: concomitant illness requiring hospitalisation 6 months previously; psychiatric ill-
ness; pregnancy
Interventions Bi-PAP versus CPAP administered at home
Prescribed inspiratory pressure was 11 mmHg ± 0.3 and expiratory pressure was 7 mmHg ± 0.3 in the Bi-
PAP group versus 10 mmHg ± 0.2 in the fixed CPAP group at baseline

2. Withdrawals
3. Tolerability
Funding & conflicts of in- 'Supported in part by Respironics'. Author conflicts not provided.
terest statements
Notes
Risk of bias
Informed decisions.
Reeves-Hoché 1995 (Continued)
Random sequence genera- Low risk Computer-generated numbers


(selection bias)

mance bias)
mance bias)
ment pressure

ment pressure
Incomplete outcome data High risk Non-completers did not contribute to analysis
(attrition bias)
All outcomes

porting bias)
Resta 2004
Methods Randomised, parallel group trial. Single-blinded study
Participants N = 20 participants (18 M/2 F). Mean age: 47 years; BMI: 37; ESS: 14
Inclusion criteria: untreated OSA; PSG-confirmed diagnosis of OSA (ASDA criteria)
Interventions Auto-CPAP versus fixed pressure CPAP. CPAP titration undertaken manually in sleep laboratory

2. ESS
3. AHI
Informed decisions.
Resta 2004 (Continued)

terest statements
Notes —
Risk of bias
Random sequence genera- Unclear risk Described as randomised; other information not available

(selection bias)
Blinding of participants High risk Quote: "...random, single-blind fashion..."

mance bias)
mance bias)
ment pressure

ment pressure
(attrition bias)
All outcomes

porting bias)
Rochford 2006
Methods Randomised, cross-over study. Statistical analysis: information not available
Participants N = 13 participants (10 M/3 F). Mean age: 48.2 years; AHI: 22.5; ESS: 11.2
Inclusion criteria: newly diagnosed OSA patients
Informed decisions.
Rochford 2006 (Continued)

Interventions Auto-CPAP (Autoset Spirit, ResMed) versus fixed CPAP
Auto-CPAP (APAP, Compumedics) versus fixed CPAP
Study duration: 3 x 4-week duration. 2-week washout

2. Symptoms (ESS)
3. AHI
5. Satisfaction

terest statements
Notes Study available as conference abstract
Risk of bias


(selection bias)

mance bias)

mance bias)
ment pressure


ment pressure

(attrition bias)
All outcomes
Informed decisions.
Rochford 2006 (Continued)

porting bias)
Rohling 2011
Methods Single-blind, randomised, cross-over trial
Participants N = 33 participants. Mean age: 52; BMI: 30.6 kg/m2; AHI: 35; ESS: 7.5
Inclusion criteria: age > 18 years, CPAP-naive with diagnosis of OSA, understand Dutch language, AHI >
15 events per hour with mild sleepiness or AHI > 5 events/hour with moderate/severe sleepiness
Exclusion criteria: central sleep apnoea, Cheyne-Stoke Respiration, severe nasal obstruction, fa-
cial/pharyngeal abnormalities, shift work, psychiatric disorder, heart failure, COPD, seizure disorder,
pregnancy, learning disability
Interventions Pressure restricted auto-adapting CPAP versus fixed CPAP
Study duration 2 x 12 weeks
Outcomes 1. Treatment pressure

2. Symptoms (ESS)
3. AHI
4. Preference

terest statements
Notes
Risk of bias
Random sequence genera- Low risk Quote: "By block randomisation of a statistical program (Randomisation pro-
tion (selection bias) gram BSR, Windows version 5.0) with a block size of 4-4-8"
Allocation concealment Low risk Quote: "Both the patient and the person who recruited the participants were
(selection bias) unaware of the allocation sequence."
Blinding of participants High risk Quote: "The trial was fully blinded to the patients. It was not possible to fully
and personnel (perfor- blind the investigator performing the analysis."
mance bias)
mance bias)
ment pressure
Informed decisions.
Rohling 2011 (Continued)
Blinding of outcome as- High risk Quote: "It was not possible to fully blind the investigator performing the analy-
sessment (detection bias) sis...The registered technologists were not aware of the group allocation of the
Machine usage, symp- patients. However they could deduct therapy as the PAP-pressure was record-
toms, quality of life, with- ed during the sleep study."
ment pressure
Incomplete outcome data High risk In both groups 3 drop-outs occurred. 17 subjects completed 6 weeks of CPAP
(attrition bias) with subsequently 6 weeks of RAPAP and 16 subjects completed 6 weeks of
All outcomes RAPAP with subsequently 6 weeks of CPAP.

porting bias)
Rostig 2003
Methods Randomised, cross-over study. Statistical analysis methods not reported.
Participants N = 30. No baseline details provided.
Participants were on long-term CPAP for OSA, but were using it for less than 4 hours per night.
Interventions Auto-CPAP (AutoSet T) versus fixed pressure CPAP

4. AHI

terest statements
Notes —
Risk of bias


(selection bias)

mance bias)
Informed decisions.
Rostig 2003 (Continued)


mance bias)
ment pressure


ment pressure

(attrition bias)
All outcomes

porting bias)
Ruhle 2011
Methods Randomised, cross-over study
Participants N = 51 participants (gender breakdown available for 44 completers: 39 M/5 F). Age 51.5; BMI: 30.9 kg/
m2; AHI: 43; ESS 10.3
Inclusion criteria: all patients referred with OSA, aged between 30 and 80 and without nasal or throat
complaints
Exclusion criteria: > 5 central apnoeas per hour of sleep, acute infection, NYHA III or IV heart failure,
acute pulmonary embolism or acute coronary syndrome. Previous use of CPAP
Interventions CPAP with heated humidification versus CPAP without heated humidification

2. Tolerability
Funding & conflicts of in- Quote: "K-H. Ruhle and G. Nilius received research funding from Fisher & Paykel Healthcare, Heinen
terest statements und Löwenstein, ResMed and Weinmann. This funding has gone into department funds. The author's
study was supported by a grant from Fisher & Paykel Healthcare Germany GmbH & Co. KG, 73636
Welzheim, Germany.Karl-Josef Franke and Ulrike Domanski have no financial or other potential conflict
of interest associated with this investigation."
Notes
Informed decisions.
Ruhle 2011 (Continued)
Risk of bias
Random sequence genera- Low risk The study had a randomised, cross-over design and used a previously pre-
tion (selection bias) pared randomisation list.
Allocation concealment Low risk Quote: "The patients were told about the group allocation only after consent.
(selection bias) The recruiting doctor was blinded to the randomisation."
Blinding of participants High risk Quote: "However, it must be kept in mind that patients knew when cHH was
and personnel (perfor- used and this may impact on the reported symptoms"
mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "The outcome assessor who calculated the study results was not blind-
sessment (detection bias) ed to the allocation."
ment pressure
Incomplete outcome data High risk Quote: "Fifty one patients were recruited, 7 dropped out during the course of
(attrition bias) the study, of which 5 were allocated to the humidification group and 2 in the
All outcomes CPAP group.....44 patients completed the study."
Selective reporting (re- Low risk All outcomes were reported

porting bias)
Ryan 2009
Participants N = 125 participants (116 M/9 F). Age: 48; BMI: 35 kg/m2; AHI: 36; ESS: 12.5
Inclusion criteria: AHI > 10, CPAP-naive, successful nasal CPAP titration study, adequate nasal breath-
ing
Exclusion criteria: Bi-PAP or supplemental oxygen; malignant disease; psychiatric disease; regular use
of narcotics; sedatives or psychoactive substances
Interventions Standard (dry) CPAP versus CPAP with heated humidification versus CPAP with nasal steroid spray
Informed decisions.
Ryan 2009 (Continued)

Outcomes 1. Machine usage (average hours used and % nights used)

3. Symptoms (ESS)
4. Tolerability (nasal symptoms measured by MiniRQLQ)
Funding & conflicts of in- Quote: "This was not an industry supported study. The authors have indicated no financial conflicts of
terest statements interest."
Notes
Risk of bias
Random sequence genera- Low risk Block randomisation was used to randomise patients to different treatment
tion (selection bias) groups
Allocation concealment Low risk Randomisation occurred centrally

(selection bias)
Blinding of participants High risk Quote: "However, patients were not blinded, since blinding would be difficult
and personnel (perfor- to achieve and requiring the use of placebo humidification, which has also
mance bias) been a limitation of previous studies."
mance bias)
ment pressure
Blinding of outcome as- High risk Although the investigators administering questionnaires and downloading
sessment (detection bias) data from the devices were blinded to the treatment arm, participants rating
Machine usage, symp- symptoms and other subjective outcomes would have been aware of the treat-
toms, quality of life, with- ment group.
ment pressure
Incomplete outcome data Unclear risk Quote: "All analyses were undertaken using the intention-to-treat principle"
(attrition bias)
All outcomes Quote: "Of the 123 patients participating in the study, 112 subjects (91%) com-
pleted the trial... Of the 10 patients wishing to discontinue
CPAP, 5 were randomized to dry treatment, 2 were commenced on addi-
tional nasal steroid, and 3 were started on additional humidification [p =
0.207])Quote: "
For dichotomous outcomes the difference in drop out was low and unlikely to
affect the size or direction of effect. For machine usage and symptom scores
dropouts may have influenced the results.
Informed decisions.
Ryan 2009 (Continued)

porting bias)
Senn 2003
Methods Randomised, cross-over study. Method of randomisation not reported.
Statistical methods: ANOVA. Unclear how within subject design accounted for in analysis.
Participants N = 31 participants. Withdrawals: N = 2. (23 M/6 F). Mean age: 53 years; BMI: 33.3 kg/m2; AHI: 45.8; ESS:
14.2
Inclusion criteria: AHI > 10 per hour; CPAP-naive
Interventions Auto-CPAP (DeVilbiss - response to apnoeas and snoring) and AutoSet T - response to apnoea and snor-
ing + flow limitation) versus fixed CPAP
Study duration: 2-week run-in with either auto-CPAP device. 3 x 4 week treatment periods.

2. Quality of life (SF-36: vitality subdomain)
3. Symptoms (ESS)
4. Sleep latency
5. AHI
Funding & conflicts of in- Quote: "Supported by the Lung League of Zurich, Lung League of Schaffhausen, Lamprecht AG & Lab-
terest statements hardt AG".
Author conflicts not provided.
Notes
Risk of bias
Random sequence genera- Unclear risk Described as randomised; no other information available

(selection bias)
Blinding of participants High risk Single-blind, cross-over study. Quote: "Patients...... were blinded to exact
and personnel (perfor- study purpose and treatment modes."
mance bias)
mance bias)
Informed decisions.
Senn 2003 (Continued)

ment pressure

ment pressure
Incomplete outcome data Low risk Low attrition rate (2 participants/31); reasons for missing data given as lack of
(attrition bias) time (N = 1), and moving away from area (N = 1)
All outcomes

porting bias)
Soudorn 2016
Methods Prospective, single-blinded, randomised, cross-over study in climate with a high humidity level. Data
analysed with paired t test
Participants N = 20 participants. (M/F 14/6). Mean age 48.9 years; BMI 28.1 kg/m2; AHI 53.7; ESS 11.5
Inclusion criteria: age > 18 years; AHI > 15 on split-night polysomnogarphy; nasopharyngeal symptoms
according to modified XERO questionnaire
Exclusion criteria: > 5 central apnoeas per hour; acute infection; heart failure with NYHA class 3 or 4;
acute pulmonary embolus; acute coronary syndrome; travel outside of Thailand within 2 months of
study baseline pattern of split-night PSG < 2 hours, less than optimal CPAP titration, use of humidifica-
tion during split-night study
Interventions CPAP with heated humidification versus conventional CPAP alone

2. AHI
3. Tolerability (mask leak)
4. Symptoms (ESS)
Funding & conflicts of in- Quote: "This work was supported by the Ratchadaphiseksomphot Endowment Fund of Chulalongko-
terest statements rn University. All CPAP machines and related equipment were sponsored by Fisher and Paykel Health-
care Limited. However, the company had no impact on study design or interpretation of the results of
the study.SR has disclosed relationships with Sanofi,Medtronic, and Merck. The other authors have dis-
closed no conflicts of interest."
Notes
Informed decisions.
Soudorn 2016 (Continued)
Risk of bias
Random sequence genera- Unclear risk Quote: "Subjects were randomly assigned by bloc sizes of 4 to receive CPAP
tion (selection bias) with or without heated humidification". Insufficient information available.
Allocation concealment Low risk Quote: "The randomisation sequence was based on the random order which
(selection bias) was in the sealed envelope prepared by our research statistician and the inves-
tigators who conducted the study and the patients were not aware of."
Blinding of participants High risk Quote: "Single blind randomized cross-over study......the subjects were blind-
and personnel (perfor- ed to the treatment arm."
mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk Single-blind study design

ment pressure
Incomplete outcome data Unclear risk Twenty-two were subjects enrolled.....Quote: "2 more subjects dropped out
(attrition bias) from the study in the first week after CPAP use, and the reasons for dropout
All outcomes were CPAP refusal." Rate of withdrawal could potentially have influenced
some outcomes
Selective reporting (re- Low risk All outcomes reported (quality of life and AHI reported as medians so could
porting bias) not be used in meta-analysis)
Sériès 1997
Methods Randomised, single-blind, parallel group study
Participants N = 36 No dropouts. Age range 36 to 65; AHI: 43.6; ESS: 15.5
Inclusion criteria: OSA confirmed by polysomnography and by clinical features; participants chosen to
be treated by CPAP
Informed decisions.
Sériès 1997 (Continued)

Exclusion criteria: life-threatening OSA (severe hypersomnolence); OSA associated with non-obstruc-
tive breathing disorders (narcolepsy); estimated pressure < 15 cmH2O. All participants were recruited
from the Hôpital Laval sleep clinic.
Interventions Auto-CPAP 1 (measured effective pressure based upon polysomnography) versus Auto-CPAP 2 (effec-
tive pressure estimated by prespecified formula) versus fixed CPAP.
Data entered from Auto-CPAP 1.
Outcomes 1. Machine usage (average hours used and N participants using machine for > 4 hours)
2. Sleep architecture
3. AHI
4. Symptoms (ESS)
5. Arousals
6. Withdrawals
Funding & conflicts of in- Funded in part by Pierre Medical France. Author declarations not provided
terest statements
Notes —
Risk of bias
Random sequence genera- Low risk Random numbers table (block of 3)


(selection bias)
Blinding of participants High risk Single-blind study

mance bias)
mance bias)
ment pressure

ment pressure
Informed decisions.
(attrition bias)
All outcomes

porting bias)
Sériès 2001
Participants N = 48. 40 had previously participated in other trials of auto and fixed CPAP. Mean age: 48; BMI: 39.5 kg/
m2
Inclusion criteria: PSG-diagnosed OSA
Exclusion criteria: corrective surgery for OSA
Interventions Auto-CPAP (Morphée) versus fixed CPAP
Outcomes 1. Machine use (average hours used)

2. Symptoms (ESS)
3. AHI
4. Withdrawals

terest statements
Notes TJL emailed for details of randomisation and outcome data 8 September 2008.
Risk of bias
Random sequence genera- Low risk Computer-generated random sequence

Allocation concealment Low risk Quote: "This was done using a binary randomisation list provided by our sta-
(selection bias) tistician who was not involved in the study."
Blinding of participants High risk Some participants had previously participated in a study and could have be-
and personnel (perfor- come aware of different devices irrespective of masking treatment group as-
mance bias) signment
mance bias)
Informed decisions.

ment pressure
Blinding of outcome as- High risk Some participants had previously participated in a study and could have be-
sessment (detection bias) come aware of different devices irrespective of masking treatment group as-
Machine usage, symp- signment
ment pressure
Incomplete outcome data Low risk Most outcomes in this review unaffected by the following exclusions:
(attrition bias)
All outcomes Quote: "The sleep stage- and body position-dependence could not be char-
acterized in 15 patients who did not change body position or whose sleep ar-
chitecture did not include REM sleep during baseline sleep recording. These
subjects were therefore excluded from the comparison between sleep stages/
body position-dependent and independent patients."

porting bias)
Teschler 2000
Methods Randomised, double-blind, cross-over study
Two-factor repeated measures analysis of variance (AVOVA). Order of testing (fixed CPAP versus au-
to-CPAP first) taken as one fixed factor, mode of treatment (fixed CPAP versus auto-CPAP as second fac-
tor)
Participants N = 10 participants (10 M). Mean age 52 years; AHI 52.9
Inclusion criteria: > 20 AHI, residence < 50 km from clinic and newly diagnosed with OSA
Exclusion criteria: co-existing airways disease (asthma/COPD), rhinitis or cardiac failure
Outcomes 1. Machine usage (average hours used and % days CPAP used)
2. AHI
3. Tolerability (leak > 0.4 L/sec)

terest statements
Notes —
Risk of bias
Informed decisions.
Teschler 2000 (Continued)
Random sequence genera- Unclear risk Described as randomised; no other information available

(selection bias)
Blinding of participants Low risk Quote: "The staff were blinded as to whether the machine was in auto or con-
and personnel (perfor- ventional mode. Patients were not told in which mode the machine was oper-
mance bias) ating."
mance bias)
ment pressure
Blinding of outcome as- Low risk Study had double-blind design.

ment pressure

(attrition bias)
All outcomes

porting bias)
To 2008
Methods Randomised, cross-over study. Statisitical analysis based on paired t test.
Participants N = 43 participants (2 lost to follow-up). BMI: 28.7 kg/m2; AHI: 54.3; ESS: 13.4
Inclusion criteria: 18 to 65 years; newly diagnosed OSA (AHI > 30)
Exclusion criteria: prior treatment for OSA
Study duration: 2 x 8 weeks (washout: 1 week)
Informed decisions.
To 2008 (Continued)
2. Symptoms (ESS)
3. AHI
5. Preference
Funding & conflicts of in- Quote: "The authors declared no conflict of interest between ResMed Company and the participating
terest statements institutions, which received no external funding support for this study."
Notes TJL emailed for clarification of data from study author
Risk of bias
Random sequence genera- Low risk Quote: "Patients were assigned by random table allocation into one of the two
tion (selection bias) arms of the study."
Allocation concealment Low risk Quote: "Randomization was performed by an investigator external to the trial.
(selection bias) The sequence of treatment group assignment was concealed from investiga-
tors conducting the screening and ongoing assessments.
Blinding of participants High risk Open-label study

mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk Open-label study

ment pressure
Incomplete outcome data Low risk Low rate of exclusions from the analysis (N = 2)
(attrition bias)
All outcomes

porting bias)
Informed decisions.
Vennelle 2010
Methods Randomised, blinded, cross-over trial. Statistical analysis based on paired tests.
Participants N = 200 participants (154 M/46 F). Mean age 50; BMI 34.5 kg/m2; AHI: 33; ESS 14
Inclusion criteria: ESS > 10 or sleepiness while driving; AHI > 15 on PSG or > 25 apnoeas/hypopneas per
hour on limited sleep study; age 18 to 75; CPAP naive
Exclusion criteria: neurological deficit compromising CPAP use; significant comorbidity; co-existing
narcolepsy/periodic limb movements; contraindication to CPAP
Interventions Fixed pressure versus variable pressure CPAP

2. Symptoms (ESS)
3. QoL (SF-36)
4. Sleep latency
5. Withdrawals
6. Tolerablity
7. Preference
Funding & conflicts of in- Quote: "This study was supported by a grant from ResMed, Poway, CA. Dr. Douglas is a shareholder in
terest statements ResMed. The other authors have indicated no additional conflicts of interest. The study was proposed,
designed and all analysis performed solely by the authors."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Patients were randomized...using a randomization schedule of bal-
tion (selection bias) anced blocks..."
Allocation concealment Low risk Quote: "Patients were randomized...by a worker otherwise uninvolved in the
(selection bias) trial."
Blinding of participants Low risk Quote: "Patients were informed that 2 different methods of giving CPAP were
and personnel (perfor- to be assessed, but were not told which was the new method"
mance bias)
Machine usage, symp- Quote: "None of the staff involved in data acquisition or analysis were aware of
toms, quality of life, with- the mode of treatment the patient was receiving"
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "The blinded staff member conducted the follow-up assessments un-
sessment (detection bias) aware of the type of CPAP the patient was using at the time of assessment."
Informed decisions.
Vennelle 2010 (Continued)
ment pressure
Incomplete outcome data High risk Quote: "Nineteen patients did not complete the study; at the time of dropout 9
(attrition bias) of these were receiving fixed and 10 variable pressure CPAP"
All outcomes
Balanced drop out which could impact on machine usage and symptoms
Selective reporting (re- High risk Side effects were rated by the Edinburgh questionnaire but not reported.
porting bias)
Wenzel 2007
Methods Randomised, single-blind, cross-over study (participants not informed of order/setting). Statistical
analysis based on Wicoxon methods (not specified if paired).
Participants N = 20 participants completed and analysed (16 M/4 F). AHI: 45; ESS: 10.9
Inclusion criteria: new diagnosis of OSA (diagnosis established through polysomnography)
Exclusion criteria: mixed or central apnoea
Interventions CPAPexp (C-Flex) versus fixed pressure CPAP
Same machine delivered the different treatment pressure settings

2. AHI
3. Symptoms (ESS)

terest statements
Notes
Risk of bias


(selection bias)
Blinding of participants High risk Quote: "....randomised, single-blinded cross-over study"

mance bias)
Informed decisions.
Wenzel 2007 (Continued)

mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "...single-blinded cross-over study"

ment pressure

(attrition bias)
All outcomes

porting bias)
West 2006
Methods Randomised, parallel group trial. Identical machines used. Withdrawals described
Participants N = 98 participants (N considered for this review: 65 (55 M/10 F). Mean age: 47; ESS: 16.
Inclusion criteria: 18 to 75 years of age; ESS > 9; proven OSA (PSG); 10 dips/hr in arterial O2 saturation;
CPAP-naive
Exclusion criteria: respiratory failure requiring urgent treatment; unable to give written consent
Participants were not excluded on the basis of comorbidities
Interventions Auto-CPAP versus algorithm established fixed CPAP
Additional treatment group not considered for this review: 1 week auto-titration followed by fixed pres-
sure at the level of 95th centile pressure from the auto-CPAP week data.

2. Symptoms (ESS)
3. Quality of life (SF-36 and SAQLI)
5. AHI
6. Withdrawals
Informed decisions.
West 2006 (Continued)
Funding & conflicts of in- Quote: "ResMed UK provided part financial support for the purchase of CPAP machines for the study
terest statements but was not involved in its design or analysis. D Jones was supported in part by a Helen Bearpark Schol-
arship from the Australasian Sleep Association and by the Sleep Apnoea Trust Association (UK). None of
the authors has any conflict of interest."
Notes —
Risk of bias
Random sequence genera- Low risk Computer generated schedule (MINIM)

Allocation concealment Low risk Quote: "...investigators carrying out the assessment studies were blind to their
(selection bias) group allocation."
Blinding of participants Low risk Quote: "The patients and the investigators carrying out the assessment stud-
and personnel (perfor- ies were blind to their group allocation."
mance bias)
mance bias)
ment pressure
Blinding of outcome as- Low risk Quote: "...the investigators carrying out the assessment studies were blind to
sessment (detection bias) their group allocation."
ment pressure
Incomplete outcome data High risk Nine participants lost to follow-up or excluded from the analysis: Quote: "No
(attrition bias) data were entered for those who did not attend."
All outcomes

porting bias)
Worsnop 2010
Methods Randomised, parallel group study
Participants N = 54 participants (43 M/11 F). Mean age 55 years; AHI 46. ESS 14
Informed decisions.
Worsnop 2010 (Continued)

Consecutive OSA patients referred for CPAP, under a program paid for by the Victorian State govern-
ment, were enrolled.
Interventions Fixed pressure CPAP + humidification versus fixed pressure CPAP alone
Outcomes • Machine usage (average hours used)

• Quality of life (SF-36)
• Symptoms ESS
• Tolerability (Nasal symptoms & resistance)
Funding & conflicts of in- Quote: "Fisher and Paykel Healthcare, Auckland, New Zealand funded this study. They were not in-
terest statements volved in the design of this study, in the collection, analysis and interpretation of data; in the writing of
the report; nor in the decision to submit the paper for publication. Author conflict of interest: None."
Notes
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation was concealed using a statistical randomisation pack-
tion (selection bias) age so that each subject was randomised to receive either treatment indepen-
dently of the other subjects."
Allocation concealment Low risk Quote: "Randomisation was concealed using a statistical randomisation pack-
(selection bias) age..."
Blinding of participants High risk Quote: "It was not possible to blind patients to the type of treatment they were
and personnel (perfor- getting"
mance bias)
mance bias)
ment pressure
Blinding of outcome as- High risk Quote: "The one CPAP therapist saw each patient at each visit. It was not pos-
sessment (detection bias) sible to blind her to the treatment that the patients were getting, but she was
Machine usage, symp- instructed not to make any attempts to determine what type of pump each pa-
toms, quality of life, with- tient was using, and to try to treat each patient in a similar manner"
ment pressure
Incomplete outcome data Low risk Quote: "All of the fifty-four subjects completed the study"
(attrition bias)
All outcomes
Informed decisions.
Worsnop 2010 (Continued)

porting bias)
ABRP-PAP: automatic bi-level therapy with pressure relief; AHI: Apnoea Hypopnoea Index; ATS: American Thoracic Society; auto-CPAP:
auto-titrating CPAP; Bi-PAP: bilevel positive airway pressure; BMI: body mass index; COPD: chronic obstructive pulmonary disease; CPAP:
continuous positive airway pressure; CPAPexp - CPAP with expiratory pressure relief; DI: desaturation index; ESS: Epworth Sleepiness Scale;
FEV1: forced expiratory volume in one second; FOSQ: Functional Outcomes of Sleep Questionnaire; FOT: forced oscillation technique;
FVC: forced vital capacity; ITT: intention-to treat-analysis; MWT: Maintenance of Wakefulness Test; nCPAP: nasal CPAP; NIV: non-invasive
ventilation; NYHA: New York Heart Association; OSA: obstructive sleep apnoea; PAP: positive airway pressure; PSG: polysomnography; RDI:
respiratory disturbance index; REM: rapid eye movement; SaO2: oxygen saturation; SAQLI: Sleep Apnoea Quality of Life Index; SF-36: Short-
Form 36 quality of life questionnaire; TST: total sleep time; UARS: upper airway resistance syndrome; UPPP: WASO: wake after sleep onset
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Al Zuheibi 2013 No fixed CPAP arm
Almasri 2007 Study of different humidifying units plus CPAP
Aloia 2001 CBT
Aloia 2004 Review article
Aloia 2005 CPAP or C-Flex given in a sequential, non-randomised order
Aloia 2005a Not randomised
Anderson 2003 Study assessing oral versus nasal interface of CPAP
Bachour 2004 Study assessing chinstrap over a 2-night laboratory titration study
Ball 2011 No fixed CPAP arm; study duration 2 days
Bardwell 2007 Placebo-controlled trial
Becker 1991 Non-randomised study of treatment failure in central sleep apnoea
Becker 1998 Review article
Berry 2002 Review article
Berthon-Jones 1996 Non-randomised study of APAP for OSA treatment
Bielicke 2008 Comparison of effects of auto-titrating CPAP (APAP) versus auto-titrating CPAP with expiratory
pressure relief (A-Flex) on AHI. No fixed CPAP arm, study duration 2 nights
Blau 2009 Comparison of auto-CPAP with A-Flex (auto-CPAP with pressure relief during expiration)
Boudewyns 1999 Non-randomised study of CPAP treatment
Bradshaw 2004 Effect of nose drops
Informed decisions.
Brammer 1999 Not randomised
Buyse 2003 Different algorithms of auto-CPAP compared
Canisius 2007 Inadequate duration
Chan 2004 Study assessing interface chamber of CPAP
Chervin 1997 Educational/psychosocial intervention
Chihara 2012 No fixed CPAP arm
Colrain 2007 Inadequate duration
Constantinidis 2000 Non-randomised study of nasal mucosal tissue changes with CPAP treatment
Coughlin 2004 CPAP versus subtherapeutic pressure of CPAP
Cross 2005 Study assessing efficacy of CPAP
Cumin 2011 Overnight study only
Damjanovic 2005 Educational/psychosocial support
Delwiche 2003 Comparison between different auto-CPAP devices
Dungan 2010 Overnight study only; no fixed CPAP arm
Duntley 2005 One-night study
Duoung 2005 One-night study
e Bastos 2013 No fixed CPAP arm
Engleman 1993 Non-randomised study of objective compliance measure of CPAP use
Epstein 2000 Educational/psychosocial intervention
Feenstra 2005 Assessment of nose drops on CPAP machine usage
Ficker 1997 Laboratory-based study
Fletcher 1991 Educational/psychosocial intervention
Fleury 1996 Non-randomised study of CPAP compliance
Gagnadoux 1999 Non-randomised study on effectiveness of AutoSet to determine treatment pressure
Galetke 2006 Manual versus auto-titrating study
Galetke 2008a No fixed CPAP arm
Informed decisions.
Galetke 2016 Control group received humidification in addition to fixed pressure CPAP
Goncalves 2006 Inadequate duration
Greenfield 2005 Placebo control
Grote 2000 Non-randomised study on CPAP compliance
Gupta 2011 Not a comparative trial of pressure modification devices in OSA
Herold 2007 Participants randomised to receive auto-CPAP as a titration strategy
Hertegonne 2003 Laboratory-based titration study
Hertegonne 2006 Split-night titration study
Horvath 2008 Different levels of Bi-PAP compared
Hosselet 1999 Review article
Hoster 1996 Laboratory-based study
Hostler 2014 No fixed CPAP arm
Hoy 1999 Educational/psychosocial intervention
Huang 2001 Non-randomised study
Hui 2000 Educational/psychosocial intervention
Hui 2001 Non-randomised study of CPAP effectiveness
Hui 2006 Different pressure levels of CPAP compared (therapeutic and subtherapeutic)
Hukins 2005 Different titration strategies compared
Husain 2003 No fixed CPAP control group
Juhàsz 2001 Two-night laboratory titration study
Khanna 2003 Comparison outside the focus of the review: oral versus nasal interface
Khayat 2007 Participants with significant cardiac comorbidity
Krieger 1992 Observational study
Krieger 1998 Non-randomised study on CPAP compliance following simplified diagnostic procedure for OSA
Krieger 1999 Review article
Likar 1997 Non-randomised study of CPAP compliance
Liu 2007 Inadequate duration
Loberes 2004 Study assessing the effects of daytime CPAP titration
Informed decisions.
Lopez-Martin 2005 Not assessment of pressure modification
Loube 2003 Laboratory based titration study
Mador 2005 Randomisation between immediate provision of humidification and delayed provision of humidifi-
cation
Mansfield 2003 Participants randomised to CPAP or inactive control
Marshall 2003 Not assessment of pressure modification
Masa 2004 Different titration strategies compared
Massie 1999 No control group receiving only fixed pressure CPAP
McArdle 2010 Comparison of effects of manual titration versus laboratory APAP titration versus home APAP titra-
tion on CPAP compliance. Participants switched to fixed CPAP after titration study
McNicholas 1997 Editorial
Meurice 1994 Non-randomised study of CPAP compliance
Meurice 1998 Randomised comparison of 2 types of auto-CPAP
Meurice 2007a Study of educational interventions
Montserrat 2006 Inadequate duration
Morley 2001 Journal correspondence
Mortimore 1998 Randomised trial comparing nose and face mask CPAP therapy
Mulgrew 2005 Different diagnostic strategies compared
Mulgrew 2006 Inadequate duration
Munoz 2009 No fixed CPAP arm
Murray 2002 Responder analysis
Neale 2011 Randomised trial comparing 6 autoadapting CPAP devices in patients previously treated with fixed
CPAP. Fixed CPAP arm not run concurrently with auto-CPAP arms
Nolan 2006 Randomisation between different auto-titrating CPAP machines; data from fixed CPAP machines
captured from start of trial
Palasiewicz 1997 Randomised study conducted when participants were awake
Peach 2003 Educational/psychosocial intervention
Penzel 2004 Laboratory-based study
Pevernagie 2004 No fixed CPAP control
Pierce 2005 Different APAP therapies compared
Informed decisions.
Pilz 2000 Laboratory-based study
Piper 2008 Participants recruited with obesity hypoventilation syndrome
Planès 2003 Randomised trial comparing auto with fixed pressure CPAP. This trial was excluded as an educa-
tional intervention administered at baseline was not standardised between the two treatment
groups. Titration was also performed in different settings for auto and fixed pressure CPAP.
Powell 2014 No fixed CPAP arm
Pradeepan 2017 Study in people with positional OSA
Pépin 1995 Non-randomised trial on side effects of nasal CPAP therapy
Rains 1996 Non-randomised study assessing educational interventions in 4 children with OSA (PsycINFO)
Randerath 1999 No fixed CPAP arm
Randerath 1999b This study compared different media for informing patients about CPAP. Overnight study
Randerath 2001a Laboratory-based study
Randerath 2003 No fixed CPAP arm
Richards 2007 Study of CBT
Rosenthal 2001 This study was excluded as participants were prescribed CPAP machines set at different hours of
use (< 6.5 hours and > 7.5 hours)
Rosenthal 2012 No fixed CPAP arm
Rubio 2015 Inadequate duration
Salgado 2006 Humidification added to APAP. No fixed pressure comparator
Scharf 1996 No attempt to measure compliance
Sharma 1996 Overnight study
Signes-Costa 2005 Assessment of different strategies to diagnose and manage OSA
Sin 2002 Non-randomised cohort study on the effects of a complex intervention on patient compliance with
CPAP therapy
Speer 2012 No fixed CPAP arm
Stammnitz 2004 Laboratory-based study
Suzuki 2007 Participants randomised to auto-CPAP or no treatment as a means of titration prior to fixed pres-
sure CPAP
Taylor 2003 Assessment of telemedicine intervention
Torvaldsson 2003 Inadequate duration (2 x 1 week treatment arms)
Informed decisions.
van der Aa 2003 Different titration strategies
Walter 2003 No fixed CPAP arm
Wiese 2005 Educational/behavioural intervention
Wiest 1999 No fixed CPAP arm
Wiest 2002 2-night titration study
Wimms 2013 Comparison of S9 (humidification with autoadjusting CPAP) versus CPAP. Not a randomised trial
AHI: Apnoea Hypopnoea Index; APAP: CBT: cognitive behavioural therapy; CPAP: continuous positive airway pressure; OSA: obstructive
sleep apnoea
Characteristics of studies awaiting assessment [ordered by study ID]
Boyer 2019
Methods Multicentre cross-over study
Participants N = 40 participants (23 M/17 F); Age: 62.4 years; BMI: 30.7 kg/m2; AHI: 46.7; ESS 8.6; FOSQ 10 29.
Inclusion criteria: diagnosis of OSA (AHI >30 (or less than 30 if respiratory arousal index >10
events/hour); no prior treatment with CPAP; using medicine known to induce nasal dryness; previ-
ous nasal symptoms or nasal surgery.
Exclusion criteria: heart failure (New York Heart Association level 3 or 4), lung disease; pregnancy;
prior treatment for OSA; >5 central oxygen saturation/hour.
Interventions 1. CPAP with humidification

2. CPAP without humidification
Study duration: 4 weeks per treatment period
Outcomes 1. Nasal and pharyngeal symptoms

2. Mask leak
4. Sleepiness (ESS)
5. Machine usage
Notes
NCT02749812
Methods Open-label, randomised controlled trial
Participants 800 adult participants not previously treated with CPAP. AHI in excess of 30 events per hour
Interventions Auto CPAP and fixed CPAP for a period of 3 months

2. ESS
Informed decisions.
NCT02749812 (Continued)
3. AHI
5. Blood pressure outcomes
The study objective is to relate effective treatment pressure with clinical outcomes and
polysomnography measurements.
Notes NCT02749812 record states that study completed in September 2015. Date registered as April 2016.
Status update (November 2018): manuscript undergoing revision by author team. Likely publica-
tion date 2nd quarter 2019.
Zamora 2019
Methods Part of large adherence trial
Participants
Interventions
Outcomes
Notes Conference abstract
AHI: Apnoea Hypopnoea Index; BMI: body mass index; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale; FOSQ:
Functional Outcomes of Sleep Questionnaire; OSA: obstructive sleep apnoea
Characteristics of ongoing studies [ordered by study ID]
ACTRN12617001090303
Trial name or title Comparing the usage of continuous positive airway pressure (PAP) against the RACer airway device
in the treatment of obstructive sleep apnoea (OSA) in naive PAP users
Methods Randomised cross-over study
Participants Planned sample size: 30. Recruitment from tertiary sleep clinic in New Zealand.
Inclusion criteria: age 18 to 70 years, no prior treatment with CPAP, ability to tolerate a nasal pil-
low mask, AHI or RDI of > 20 events per hour
Interventions Standard CPAP device or Rest-Activity-Cycle (RACer) system used with positive airway pressure de-
vice (RACer CPAP). The RACer device delivers pressurised air into the upper airway into one nostril
at a time. Both modalities are combined in a single device, although RACer mode necessitates the
use of nasal pillow.
Planned duration: 4 weeks of treatment on each arm either side of a 3-day washout period be-
tween arms.
Outcomes 1. Machine usage each night averaged over last two weeks of treatment period
2. AHI
3. Symptoms (ESS)
4. Quality of life (SF-36 questionnaire)
5. Comfort of each device assessed by in-house questionnaire
Starting date 20/09/2017
Informed decisions.
ACTRN12617001090303 (Continued)
Contact information Dr Angela Campbell
WellSleep
University of Otago, Wellington
98 Churchill Drive
Crofton Downs, 6035
Wellington
Notes
ACTRN12618000379213p
Trial name or title Auto-titrating versus fixed continuous positive airway pressure in obesity hypoventilation syn-
drome
Methods Randomised parallel group trial
Participants Planned sample size: 40
Inclusion criteria: age 18 to 80 years; BMI > 30; PaCO2 45 mmHg to 60 mmHg; blood pH 7.35 to
7.45; no use of CPAP in the past 12 months; AHI ≥ 30
Interventions Fixed CPAP versus auto-CPAP
Outcomes 1. PaCO2 at 3 months

2. Cardiovascular markers (HbA1C, Lipid profile,
4. Sleepiness (ESS)
5. Nocturnal oximetry
6. Machine usage
7. AHI
8. Adverse events
Starting date May 2018
Contact information Dr Yizhong Zheng
Department of Respiratory and Sleep Medicine

50 Missenden Rd
Camperdown
NSW 2050
Australia
Notes
Informed decisions.
Morton 2001
Trial name or title The effects of humidification of nasal CPAP on adherence, compliance, patient satisfaction and
symptoms: a preliminary report
Methods NA
Participants 80 recruited. 40 completed protocol. Mean age 52.2 (10.3). 32 M: 8 F. 5 dropped out.
Interventions CPAP with humidifier versus CPAP without humidifier for 3/12
Outcomes • Symptom scores (ESS)

• Satisfaction on analogue scale
• Quality of life (SF36)
• Usage
Starting date Not stated
Contact information Sharon Morton, Flinders Medical Centre Bedford Pk.
Notes
NCT01753999
Trial name or title None given
Methods Double-blind cross-over randomised trial. Randomisation sequence generated by computer
Participants 400 planned as per published protocol (440 planned as per CT.gov record). Participants recruited
from responders exposed to dust from collapse of World Trade Centre in 2001.
Inclusion criteria: nasal resistance and sleep apnoea diagnosed by home-based study
Interventions Fixed pressure CPAP and flexible CPAP (CPAPFlex)
Treatment arms scheduled to last for 4 weeks in published protocol (9 weeks according to CT.gov
record)
Outcomes 1. Machine usage taken as average over last 2 weeks of treatment

2. AHI
3. Symptoms (ESS)
5. Treatment satisfaction
Starting date December 2012
Contact information
Notes
Informed decisions.
NCT03428516
Trial name or title Decrease in sympathetic tone in OSA patients: Is CPAP more effective than APAP?
Methods Randomised parallel group
Participants Planned sample size: 68
Inclusion criteria: AHI ≥ 20; daytime sleepiness; no prior exposure to CPAP
Exclusion criteria: serious heart failure; central sleep apnoea index above 20% of AHI; serious co-
morbidity
Interventions Fixed CPAP versus auto-CPAP
Outcomes 1. Sympathetic tone measured (muscle sympathetic neural activity)

2. Blood pressure
3. Heart rate
4. Catecholamine levels
Starting date 1 March 2018
Contact information Renaud Tamisier, MD, PhD
University Hospital
Grenoble
France
Notes
Ventateswaren 2003
Trial name or title Not available
Methods Randomised, cross-over study
Participants 5 recruited
Interventions Auto-CPAP versus CPAP for 2/52
Outcomes Heart rate variability
Starting date Not stated
Contact information —
Notes TJL emailed for data 14 November 2008
AHI: Apnoea Hypopnoea Index; BMI: body mass index; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale; FOSQ:
Functional Outcomes of Sleep Questionnaire; OSA: obstructive sleep apnoea; PaCO2: partial pressure of arterial carbon dioxide; RDI:
Respiratory Disturbance Index; SF-36: Short-Form 36; SAQLI: Sleep Apnoea Quality of Life Index
Informed decisions.
DATA AND ANALYSES
Comparison 1. Auto-CPAP versus fixed CPAP
Outcome or subgroup title No. of No. of Statistical method Effect size

studies partici-
pants
1 Machine usage (hours/night) 31 1452 Mean Difference (Fixed, 95% CI) 0.21 [0.11, 0.31]
2 Machine usage (hours/night) (Pepin im- 32 1774 Mean Difference (Fixed, 95% CI) 0.19 [0.10, 0.29]
puted)
3 Number of participants who used CPAP 2 346 Odds Ratio (M-H, Fixed, 95% CI) 1.16 [0.75, 1.81]
therapy > 4 hours per night
4 Machine usage (on nights when CPAP 3 Mean Difference (Fixed, 95% CI) 0.42 [0.05, 0.78]
used 'effectively')
5 Machine usage (frequency of usage as % 9 Mean Difference (Fixed, 95% CI) 1.60 [-0.83, 4.03]
of days)
6 Machine usage (% of nights of > 4 hours 2 Mean Difference (Fixed, 95% CI) 6.25 [-0.05, 12.54]
of use) - cross-over studies
7 Symptoms (Epworth Sleepiness Scale) 25 1285 Mean Difference (Fixed, 95% CI) -0.44 [-0.72, -0.16]
8 Withdrawals (parallel group trials/first 13 1275 Odds Ratio (M-H, Fixed, 95% CI) 0.90 [0.64, 1.27]
arm cross-over trials)
9 Quality of life (Functional Outcomes of 3 352 Mean Difference (Fixed, 95% CI) 0.12 [-0.21, 0.46]
Sleep Questionnaire)
10 Quality of life (Sleep Apnoea Quality of 2 97 Mean Difference (Fixed, 95% CI) -0.14 [-0.54, 0.27]
Life Index)
11 Quality of life (SF-36 questionnaire) 8 Mean Difference (Fixed, 95% CI) Subtotals only
11.1 Physical functioning 3 Mean Difference (Fixed, 95% CI) 0.76 [-3.50, 5.01]
11.2 Role physical 2 Mean Difference (Fixed, 95% CI) -3.73 [-13.46, 6.01]
11.3 Bodily pain 2 Mean Difference (Fixed, 95% CI) 4.21 [-4.23, 12.64]
11.4 General health 2 Mean Difference (Fixed, 95% CI) 2.49 [-4.99, 9.97]
11.5 Vitality 6 Mean Difference (Fixed, 95% CI) 1.32 [-1.25, 3.88]
11.6 Social functioning 2 Mean Difference (Fixed, 95% CI) 3.31 [-4.29, 10.92]
11.7 Role emotional 3 Mean Difference (Fixed, 95% CI) 0.70 [-4.19, 5.59]
11.8 Mental health 3 Mean Difference (Fixed, 95% CI) 0.20 [-1.88, 2.27]
12 Apnoea Hypopnoea Index (events/hr) 26 1256 Mean Difference (Fixed, 95% CI) 0.48 [0.16, 0.80]
Informed decisions.

studies partici-
pants
13 Arousals (events/hr) 4 136 Mean Difference (Fixed, 95% CI) -0.66 [-2.90, 1.58]
14 Pressure of CPAP treatment (cmH2O) 24 1171 Mean Difference (Fixed, 95% CI) -1.01 [-1.17, -0.84]
15 Systolic blood pressure 2 353 Mean Difference (IV, Fixed, 95% 1.87 [-1.08, 4.82]
CI)
16 Diastolic blood pressure 2 353 Mean Difference (IV, Fixed, 95% 2.92 [1.06, 4.77]
CI)
17 24-hour mean BP 2 530 Mean Difference (IV, Fixed, 95% 0.59 [-1.05, 2.22]
CI)
18 24-hour systolic BP 2 530 Mean Difference (IV, Fixed, 95% -0.15 [-2.21, 1.91]
CI)
19 24-hour diastolic BP 2 530 Mean Difference (IV, Fixed, 95% 0.90 [-0.65, 2.44]
CI)
20 Diurnal mean BP 2 530 Mean Difference (IV, Fixed, 95% 0.63 [-1.05, 2.32]
CI)
21 Diurnal systolic BP 2 530 Mean Difference (IV, Fixed, 95% -0.35 [-2.44, 1.74]
CI)
22 Diurnal diastolic BP 2 530 Mean Difference (IV, Fixed, 95% 0.91 [-0.74, 2.55]
CI)
23 Nocturnal mean BP 2 530 Mean Difference (IV, Fixed, 95% 0.43 [-1.29, 2.15]
CI)
24 Nocturnal systolic BP 2 530 Mean Difference (IV, Fixed, 95% 0.88 [-1.81, 3.57]
CI)
25 Nocturnal diastolic BP 2 530 Mean Difference (IV, Fixed, 95% 0.80 [-0.81, 2.40]
CI)
26 Tolerability outcomes 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
26.1 Intolerable treatment pressure 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
26.2 Mask leak 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
26.3 Dry mouth 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
26.4 Stuffy nose 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
27 Patient preference (auto-CPAP/not au- 14 Odds Ratio (M-H, Random, 95% Totals not selected
to-CPAP) CI)
Informed decisions.
Analysis 1.1. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).
Study or subgroup Auto-CPAP Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
ference
N N (SE) IV, Fixed, 95% CI IV, Fixed, 95% CI
Berry 2014 67 64 0.5 (0.402) 1.6% 0.45[-0.34,1.24]
Bloch 2018 113 95 -0.2 (0.283) 3.22% -0.2[-0.75,0.35]
Chang 2015 19 0 0.3 (0.441) 1.33% 0.3[-0.56,1.16]
d'Ortho 2000 25 0 -0.6 (0.462) 1.21% -0.6[-1.5,0.3]
Damjanovic 2009 25 25 0.1 (0.499) 1.04% 0.1[-0.88,1.08]
Ficker 2003 50 50 0.6 (0.369) 1.89% 0.6[-0.12,1.32]
Fietze 2007 10 11 0.8 (0.834) 0.37% 0.8[-0.84,2.44]
Galetke 2008 20 0 -0 (0.587) 0.75% -0.01[-1.16,1.14]
Hudgel 2000 29 0 0.8 (0.647) 0.62% 0.76[-0.51,2.03]
Hukins 2004 46 0 0.2 (0.13) 15.26% 0.19[-0.06,0.44]
Hussain 2004 10 0 0.6 (1.02) 0.25% 0.6[-1.4,2.6]
Jarvis 2006 20 0 -0 (0.202) 6.35% -0.04[-0.43,0.36]
Konermann 1998 25 23 0.3 (0.594) 0.73% 0.3[-0.86,1.46]
Marrone 2004 22 0 0.5 (0.55) 0.85% 0.5[-0.58,1.58]
Massie 2003 44 0 0.6 (0.207) 6.04% 0.58[0.18,0.98]
Meurice 1996 8 8 1.4 (0.526) 0.93% 1.4[0.37,2.43]
Meurice 2007 51 17 -0.6 (0.538) 0.89% -0.6[-1.65,0.45]
Nolan 2007 29 0 0 (0.525) 0.94% 0[-1.03,1.03]
Nussbaumer 2006 30 0 0.3 (0.423) 1.44% 0.3[-0.53,1.13]
Patruno 2007 16 15 0.2 (0.327) 2.42% 0.2[-0.44,0.84]
Randerath 2001 45 0 0 (0.31) 2.68% 0[-0.61,0.61]
Resta 2004 10 10 -0.1 (0.721) 0.5% -0.1[-1.51,1.31]
Rochford 2006 13 0 0.1 (0.786) 0.42% 0.1[-1.44,1.64]
Rostig 2003 30 0 0.5 (0.238) 4.56% 0.5[0.03,0.97]
Senn 2003 29 0 -0.1 (0.28) 3.29% -0.1[-0.65,0.45]
Sériès 1997 12 12 -0.1 (0.393) 1.67% -0.1[-0.87,0.67]
Sériès 2001 17 16 0.6 (0.37) 1.89% 0.57[-0.15,1.29]
Teschler 2000 10 0 0.2 (0.638) 0.63% 0.2[-1.05,1.45]
To 2008 41 0 0.3 (0.163) 9.67% 0.26[-0.06,0.58]
Vennelle 2010 181 0 0.2 (0.1) 25.61% 0.2[0,0.4]
West 2006 28 31 0.4 (0.515) 0.97% 0.43[-0.58,1.44]
Total (95% CI) 100% 0.21[0.11,0.31]

Heterogeneity: Tau2=0; Chi2=26.09, df=30(P=0.67); I2=0%
Test for overall effect: Z=4.22(P<0.0001)
Fixed CPAP better -2 -1 0 1 2 Auto-CPAP better
Analysis 1.2. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 2 Machine usage (hours/night) (Pepin imputed).
ference
Berry 2014 67 64 0.5 (0.402) 1.49% 0.45[-0.34,1.24]
Bloch 2018 113 95 -0.2 (0.283) 3.01% -0.2[-0.75,0.35]
Chang 2015 19 0 0.3 (0.441) 1.24% 0.3[-0.56,1.16]
d'Ortho 2000 25 0 -0.6 (0.462) 1.13% -0.6[-1.5,0.3]
Damjanovic 2009 25 25 0.1 (0.499) 0.97% 0.1[-0.88,1.08]
Informed decisions.
ference
Ficker 2003 50 50 0.6 (0.369) 1.76% 0.6[-0.12,1.32]
Fietze 2007 10 11 0.8 (0.834) 0.35% 0.8[-0.84,2.44]
Galetke 2008 20 0 -0 (0.587) 0.7% -0.01[-1.16,1.14]
Hudgel 2000 29 0 0.8 (0.647) 0.57% 0.76[-0.51,2.03]
Hukins 2004 46 0 0.2 (0.13) 14.24% 0.19[-0.06,0.44]
Hussain 2004 10 0 0.6 (1.02) 0.23% 0.6[-1.4,2.6]
Jarvis 2006 20 0 -0 (0.202) 5.93% -0.04[-0.43,0.36]
Konermann 1998 25 23 0.3 (0.594) 0.68% 0.3[-0.86,1.46]
Marrone 2004 22 0 0.5 (0.55) 0.8% 0.5[-0.58,1.58]
Massie 2003 44 0 0.6 (0.207) 5.64% 0.58[0.18,0.98]
Meurice 1996 8 8 1.4 (0.526) 0.87% 1.4[0.37,2.43]
Meurice 2007 51 17 -0.6 (0.538) 0.83% -0.6[-1.65,0.45]
Nolan 2007 29 0 0 (0.525) 0.87% 0[-1.03,1.03]
Nussbaumer 2006 30 0 0.3 (0.423) 1.34% 0.3[-0.53,1.13]
Patruno 2007 16 15 0.2 (0.327) 2.26% 0.2[-0.44,0.84]
Pépin 2016 161 161 -0.1 (0.19) 6.7% -0.1[-0.47,0.27]
Randerath 2001 45 0 0 (0.31) 2.5% 0[-0.61,0.61]
Resta 2004 10 10 -0.1 (0.721) 0.46% -0.1[-1.51,1.31]
Rochford 2006 13 0 0.1 (0.786) 0.39% 0.1[-1.44,1.64]
Rostig 2003 30 0 0.5 (0.238) 4.25% 0.5[0.03,0.97]
Senn 2003 29 0 -0.1 (0.28) 3.07% -0.1[-0.65,0.45]
Sériès 1997 12 12 -0.1 (0.393) 1.56% -0.1[-0.87,0.67]
Sériès 2001 17 16 0.6 (0.37) 1.76% 0.57[-0.15,1.29]
Teschler 2000 10 0 0.2 (0.638) 0.59% 0.2[-1.05,1.45]
To 2008 41 0 0.3 (0.163) 9.03% 0.26[-0.06,0.58]
Vennelle 2010 181 0 0.2 (0.1) 23.89% 0.2[0,0.4]
West 2006 28 31 0.4 (0.515) 0.91% 0.43[-0.58,1.44]
Total (95% CI) 100% 0.19[0.1,0.29]

Analysis 1.3. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 3

Number of participants who used CPAP therapy > 4 hours per night.
Study or subgroup Auto-CPAP Fixed CPAP Odds Ratio Weight Odds Ratio
n/N n/N M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Pépin 2016 107/161 104/161 95.88% 1.09[0.69,1.72]
Sériès 1997 6/12 3/12 4.12% 3[0.53,16.9]
Total (95% CI) 173 173 100% 1.16[0.75,1.81]

Total events: 113 (Auto-CPAP), 107 (Fixed CPAP)
Heterogeneity: Tau2=0; Chi2=1.24, df=1(P=0.27); I2=19.35%
Test for overall effect: Z=0.68(P=0.5)
Fixed CPAP better 0.002 0.1 1 10 500 Auto-CPAP better
Informed decisions.
Analysis 1.4. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome

4 Machine usage (on nights when CPAP used 'effectively').
ference
Hudgel 2000 29 29 0.5 (0.23) 65.3% 0.5[0.05,0.95]
Marrone 2004 22 22 0.3 (0.41) 20.55% 0.3[-0.5,1.1]
Noseda 2004 24 24 0.2 (0.494) 14.15% 0.2[-0.77,1.17]
Total (95% CI) 100% 0.42[0.05,0.78]

Analysis 1.5. Comparison 1 Auto-CPAP versus fixed CPAP,

Outcome 5 Machine usage (frequency of usage as % of days).
ference
Chang 2015 0 0 -0.5 (1.884) 43.22% -0.5[-4.19,3.19]
Damjanovic 2009 0 0 -1.3 (6.999) 3.13% -1.3[-15.02,12.42]
Hudgel 2000 33 33 2 (5.65) 4.81% 2[-9.07,13.07]
Hukins 2004 46 46 5.3 (4.913) 6.36% 5.3[-4.33,14.93]
Marrone 2004 22 22 5.3 (5.12) 5.85% 5.3[-4.74,15.34]
Massie 2003 44 44 4 (2.806) 19.49% 4[-1.5,9.5]
Nolan 2007 29 29 -2.2 (6.99) 3.14% -2.2[-15.9,11.5]
Teschler 2000 10 10 2.1 (3.83) 10.46% 2.1[-5.41,9.61]
West 2006 0 0 5.2 (6.589) 3.53% 5.24[-7.67,18.15]
Total (95% CI) 100% 1.6[-0.83,4.03]

Analysis 1.6. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 6

Machine usage (% of nights of > 4 hours of use) - cross-over studies.
ference
Hudgel 2000 29 29 7 (3.71) 74.85% 7[-0.27,14.27]
Nussbaumer 2006 30 30 4 (6.4) 25.15% 4[-8.54,16.54]
Total (95% CI) 100% 6.25[-0.05,12.54]

Informed decisions.
Analysis 1.7. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 7 Symptoms (Epworth Sleepiness Scale).
ference
Berry 2014 67 64 0.2 (0.776) 3.39% 0.2[-1.32,1.72]
Bloch 2018 113 95 -0.3 (0.566) 6.37% -0.3[-1.41,0.81]
d'Ortho 2000 25 0 0.1 (2.155) 0.44% 0.1[-4.12,4.32]
Damjanovic 2009 25 25 -0.7 (0.99) 2.08% -0.7[-2.64,1.24]
Ficker 2003 50 50 -0.6 (0.782) 3.34% -0.6[-2.13,0.93]
Galetke 2008 20 0 -1.7 (1.487) 0.92% -1.7[-4.61,1.21]
Hudgel 2000 29 0 1 (1.55) 0.85% 1[-2.04,4.04]
Hukins 2004 46 0 -0.5 (1.04) 1.89% -0.5[-2.54,1.54]
Hussain 2004 10 0 1.4 (2.59) 0.3% 1.4[-3.68,6.48]
Marrone 2004 22 0 -1 (0.989) 2.08% -1[-2.94,0.94]
Massie 2003 44 0 -1 (0.852) 2.81% -1[-2.67,0.67]
Meurice 1996 8 8 -3 (2.768) 0.27% -3[-8.43,2.43]
Meurice 2007 51 17 0.6 (1.496) 0.91% 0.6[-2.33,3.53]
Nolan 2007 29 0 0.9 (0.97) 2.17% 0.9[-1,2.8]
Noseda 2004 24 0 -1 (0.36) 15.74% -1[-1.71,-0.29]
Nussbaumer 2006 30 0 -0.2 (0.689) 4.3% -0.25[-1.6,1.1]
Resta 2004 10 10 1.1 (1.018) 1.97% 1.1[-0.9,3.1]
Rochford 2006 13 0 -0.3 (2.424) 0.35% -0.3[-5.05,4.45]
Rohling 2011 33 0 0 (0.591) 5.84% 0[-1.16,1.16]
Senn 2003 29 0 0.7 (2.17) 0.43% 0.7[-3.55,4.95]
Sériès 1997 12 12 -0.8 (1.75) 0.67% -0.8[-4.23,2.63]
Sériès 2001 17 16 -1.4 (1.5) 0.91% -1.4[-4.34,1.54]
To 2008 41 0 0 (1.273) 1.26% 0[-2.49,2.49]
Vennelle 2010 181 0 -0.5 (0.23) 38.55% -0.5[-0.95,-0.05]
West 2006 28 31 0.1 (0.968) 2.18% 0.06[-1.84,1.96]
Total (95% CI) 100% -0.44[-0.72,-0.16]

Test for overall effect: Z=3.11(P=0)
Auto-CPAP better -10 -5 0 5 10 Fixed CPAP better

8 Withdrawals (parallel group trials/first arm cross-over trials).
Berry 2014 9/78 14/78 18.46% 0.6[0.24,1.47]
Bloch 2018 21/113 15/95 19.78% 1.22[0.59,2.52]
Konermann 1998 0/25 2/25 3.66% 0.18[0.01,4.04]
Meurice 1996 0/8 0/8 Not estimable
Meurice 2007 15/66 0/17 0.9% 10.53[0.6,185.4]
Noseda 2004 2/14 1/13 1.33% 2[0.16,25.11]
Pépin 2016 16/161 25/161 33.57% 0.6[0.31,1.17]
Randerath 2001 2/24 2/28 2.52% 1.18[0.15,9.09]
Rohling 2011 3/19 3/20 3.67% 1.06[0.19,6.05]
Sériès 1997 0/12 0/12 Not estimable
Auto-CPAP better 0.005 0.1 1 10 200 Fixed CPAP better
Informed decisions.
Sériès 2001 0/17 0/16 Not estimable
Vennelle 2010 8/100 8/100 10.97% 1[0.36,2.78]
West 2006 3/31 4/34 5.14% 0.8[0.17,3.91]
Total (95% CI) 668 607 100% 0.9[0.64,1.27]

Total events: 79 (Auto-CPAP), 74 (Fixed CPAP)

9 Quality of life (Functional Outcomes of Sleep Questionnaire).
ference
Berry 2014 67 64 -0.3 (0.593) 8.5% -0.3[-1.46,0.86]
Bloch 2018 113 95 0.4 (0.283) 37.32% 0.4[-0.15,0.95]
Rochford 2006 13 0 0 (0.235) 54.18% 0[-0.46,0.46]
Total (95% CI) 100% 0.12[-0.21,0.46]

Favours fixed CPAP -5 -2.5 0 2.5 5 Favours auto-CPAP

Outcome 10 Quality of life (Sleep Apnoea Quality of Life Index).
ference
To 2008 41 0 0 (0.283) 53.11% 0[-0.55,0.55]
West 2006 26 30 -0.3 (0.301) 46.89% -0.29[-0.88,0.3]
Total (95% CI) 100% -0.14[-0.54,0.27]

Fixed CPAP better -5 -2.5 0 2.5 5 Auto CPAP better
Analysis 1.11. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 11 Quality of life (SF-36 questionnaire).
ference
1.11.1 Physical functioning
Fixed CPAP better -20 -10 0 10 20 Auto CPAP better
Informed decisions.
ference
Chang 2015 0 0 -0.3 (5.26) 17.02% -0.3[-10.61,10.01]
Meurice 2007 0 0 1.4 (2.627) 68.22% 1.4[-3.75,6.55]
Nussbaumer 2006 30 30 -1 (5.65) 14.75% -1[-12.07,10.07]
Subtotal (95% CI) 100% 0.76[-3.5,5.01]
1.11.2 Role physical

Chang 2015 0 0 4 (10.422) 22.71% 4[-16.43,24.43]
Nussbaumer 2006 30 30 -6 (5.65) 77.29% -6[-17.07,5.07]
Subtotal (95% CI) 100% -3.73[-13.46,6.01]
1.11.3 Bodily pain

Chang 2015 0 0 8.5 (5.812) 54.83% 8.5[-2.89,19.89]
Nussbaumer 2006 30 30 -1 (6.403) 45.17% -1[-13.55,11.55]
Subtotal (95% CI) 100% 4.21[-4.23,12.64]
1.11.4 General health

Chang 2015 0 0 -2.4 (5.905) 41.76% -2.4[-13.97,9.17]
Nussbaumer 2006 30 30 6 (5) 58.24% 6[-3.8,15.8]
Subtotal (95% CI) 100% 2.49[-4.99,9.97]
1.11.5 Vitality
Bloch 2018 0 0 -4 (2.828) 21.39% -4[-9.54,1.54]
Chang 2015 0 0 -0.2 (5.63) 5.4% -0.2[-11.23,10.83]
Hukins 2004 46 46 3 (1.98) 43.66% 3[-0.88,6.88]
Massie 2003 44 44 7 (3.52) 13.81% 7[0.1,13.9]
Nussbaumer 2006 30 30 1 (4.24) 9.52% 1[-7.31,9.31]
Senn 2003 29 29 -3 (5.247) 6.22% -3[-13.28,7.28]
Subtotal (95% CI) 100% 1.32[-1.25,3.88]
1.11.6 Social functioning

Chang 2015 0 0 5.3 (6.148) 39.81% 5.3[-6.75,17.35]
Nussbaumer 2006 30 30 2 (5) 60.19% 2[-7.8,11.8]
Subtotal (95% CI) 100% 3.31[-4.29,10.92]
1.11.7 Role emotional

Chang 2015 0 0 -1.8 (13.448) 3.44% -1.8[-28.16,24.56]
Meurice 2007 0 0 -0.9 (2.82) 78.25% -0.9[-6.43,4.63]
Nussbaumer 2006 30 30 8 (5.832) 18.3% 8[-3.43,19.43]
Subtotal (95% CI) 100% 0.7[-4.19,5.59]
Informed decisions.
ference
1.11.8 Mental health

Chang 2015 0 0 1.5 (4.185) 6.39% 1.5[-6.7,9.7]
Nussbaumer 2006 30 30 3 (4.24) 6.22% 3[-5.31,11.31]
Vennelle 2010 0 0 -0.1 (1.131) 87.39% -0.1[-2.32,2.12]
Subtotal (95% CI) 100% 0.2[-1.88,2.27]
Analysis 1.12. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 12 Apnoea Hypopnoea Index (events/hr).
ference
Berry 2014 67 64 0.6 (0.861) 3.66% 0.6[-1.09,2.29]
Bloch 2018 113 95 0.3 (2.092) 0.62% 0.3[-3.8,4.4]
Chang 2015 19 0 1.8 (0.523) 9.93% 1.8[0.77,2.83]
d'Ortho 2000 25 0 0.9 (2.52) 0.43% 0.9[-4.04,5.84]
Damjanovic 2009 25 25 -1.8 (1.613) 1.04% -1.8[-4.96,1.36]
Ficker 2003 50 50 0 (0.709) 5.4% 0[-1.39,1.39]
Fietze 2007 10 11 0.5 (1.684) 0.96% 0.5[-2.8,3.8]
Galetke 2008 20 0 1 (1.036) 2.53% 1[-1.03,3.03]
Hussain 2004 10 10 3.5 (3.13) 0.28% 3.5[-2.63,9.63]
Jarvis 2006 20 0 0.8 (0.677) 5.93% 0.81[-0.52,2.13]
Konermann 1998 25 23 -1.2 (0.972) 2.88% -1.2[-3.1,0.7]
Massie 2003 44 0 -1.1 (1.276) 1.67% -1.1[-3.6,1.4]
Meurice 1996 8 8 -0.9 (1.142) 2.08% -0.9[-3.14,1.34]
Nolan 2007 29 0 -0.6 (0.857) 3.7% -0.6[-2.28,1.08]
Nussbaumer 2006 30 0 -0.8 (1.276) 1.67% -0.8[-3.3,1.7]
Patruno 2007 16 15 4 (0.716) 5.3% 4[2.6,5.4]
Randerath 2001 45 0 0.7 (1.13) 2.13% 0.7[-1.51,2.91]
Resta 2004 10 10 -0.1 (1.302) 1.6% -0.1[-2.65,2.45]
Rochford 2006 13 0 -0.7 (0.786) 4.4% -0.7[-2.24,0.84]
Rostig 2003 30 0 0.5 (1.14) 2.09% 0.5[-1.73,2.73]
Senn 2003 29 0 0.7 (1.414) 1.36% 0.7[-2.07,3.47]
Sériès 1997 12 12 -0.5 (1.268) 1.69% -0.5[-2.98,1.98]
Sériès 2001 17 16 -1 (0.867) 3.62% -0.96[-2.66,0.74]
Teschler 2000 10 0 0.3 (1.34) 1.51% 0.3[-2.33,2.93]
Vennelle 2010 181 0 0.4 (0.291) 32.19% 0.4[-0.17,0.97]
West 2006 28 31 0.6 (1.432) 1.33% 0.55[-2.26,3.36]
Total (95% CI) 100% 0.48[0.16,0.8]

Heterogeneity: Tau2=0; Chi2=49.01, df=25(P=0); I2=48.99%
Auto-CPAP better -5 -2.5 0 2.5 5 Fixed CPAP better
Informed decisions.
Analysis 1.13. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 13 Arousals (events/hr).
ference
Damjanovic 2009 25 25 2.1 (4.456) 6.56% 2.12[-6.61,10.86]
Hussain 2004 10 0 1 (2.367) 23.26% 1[-3.64,5.64]
Randerath 2001 52 0 -1.7 (1.398) 66.7% -1.7[-4.44,1.04]
Sériès 1997 12 12 3 (6.125) 3.47% 2.97[-9.03,14.98]
Total (95% CI) 100% -0.66[-2.9,1.58]

Auto-CPAP better -20 -10 0 10 20 Fixed CPAP better
Analysis 1.14. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 14 Pressure of CPAP treatment (cmH2O).
ference
Berry 2014 67 64 -0.9 (0.501) 2.85% -0.9[-1.88,0.08]
Bloch 2018 113 95 -1.8 (0.361) 5.51% -1.8[-2.51,-1.09]
Chang 2015 19 0 -1.2 (0.488) 3.01% -1.2[-2.16,-0.24]
d'Ortho 2000 25 0 -0.9 (0.633) 1.79% -0.9[-2.14,0.34]
Damjanovic 2009 25 25 -1 (0.36) 5.53% -1[-1.71,-0.29]
Ficker 2003 50 50 -3 (0.381) 4.95% -3[-3.75,-2.25]
Fietze 2007 10 11 1 (0.734) 1.33% 1[-0.44,2.44]
Galetke 2008 20 0 -0.1 (0.347) 5.95% -0.1[-0.78,0.58]
Hudgel 2000 29 0 -4.2 (0.566) 2.23% -4.2[-5.31,-3.09]
Hukins 2004 46 0 -3.5 (0.735) 1.33% -3.5[-4.94,-2.06]
Hussain 2004 10 0 -5 (1.403) 0.36% -5[-7.75,-2.25]
Jarvis 2006 20 0 -4.7 (0.5) 2.87% -4.69[-5.67,-3.71]
Konermann 1998 25 23 -1.6 (0.605) 1.96% -1.6[-2.79,-0.41]
Massie 2003 22 0 -3.8 (0.383) 4.89% -3.8[-4.55,-3.05]
Meurice 1996 8 8 0.4 (1.55) 0.3% 0.4[-2.64,3.44]
Noseda 2004 24 0 -0.9 (0.648) 1.71% -0.9[-2.17,0.37]
Nussbaumer 2006 30 0 -1.3 (0.643) 1.73% -1.3[-2.56,-0.04]
Randerath 2001 45 0 -1.2 (0.393) 4.64% -1.2[-1.97,-0.43]
Rohling 2011 33 0 -0.5 (0.48) 3.11% -0.5[-1.44,0.44]
Rostig 2003 30 0 -1 (0.505) 2.81% -1[-1.99,-0.01]
Senn 2003 29 0 -2 (0.566) 2.23% -2[-3.11,-0.89]
Sériès 1997 12 12 0.3 (0.388) 4.75% 0.3[-0.46,1.06]
Teschler 2000 10 0 0.7 (0.781) 1.18% 0.7[-0.83,2.23]
Vennelle 2010 181 0 0.1 (0.147) 32.98% 0.1[-0.19,0.39]
Total (95% CI) 100% -1.01[-1.17,-0.84]

Heterogeneity: Tau2=0; Chi2=284.69, df=23(P<0.0001); I2=91.92%
Auto-CPAP lower -10 -5 0 5 10 Fixed CPAP lower
Informed decisions.
Analysis 1.15. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 15 Systolic blood pressure.
Study or subgroup Auto-CPAP Fixed pres- Mean Difference Weight Mean Difference
sure CPAP
N Mean(SD) N Mean(SD) Fixed, 95% CI Fixed, 95% CI
Patruno 2007 15 136 (6) 16 132 (8) 35.46% 4[-0.96,8.96]
Pépin 2016 161 134.3 (17.7) 161 133.6 (15.9) 64.54% 0.7[-2.98,4.38]
Total *** 176 177 100% 1.87[-1.08,4.82]

Favours auto-CPAP -20 -10 0 10 20 Favours fixed CPAP
Analysis 1.16. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 16 Diastolic blood pressure.
Study or subgroup Auto-CPAP Fixed pres- Mean Difference Weight Mean Difference
sure CPAP
Patruno 2007 15 86 (4) 16 79 (6) 27.09% 7[3.43,10.57]
Pépin 2016 161 78.2 (9.5) 161 76.8 (10.4) 72.91% 1.4[-0.78,3.58]
Total *** 176 177 100% 2.92[1.06,4.77]

Favours auto-CPAP -20 -10 0 10 20 Favours fixed CPAP
Analysis 1.17. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 17 24-hour mean BP.
Study or subgroup Auto-CPAP Fixed CPAP Mean Difference Weight Mean Difference
Bloch 2018 113 92 (10.6) 95 92 (9.7) 34.96% 0[-2.77,2.77]
Pépin 2016 161 94.5 (9.1) 161 93.6 (9.5) 65.04% 0.9[-1.13,2.93]
Total *** 274 256 100% 0.59[-1.05,2.22]

Favours auto-CPAP -5 -2.5 0 2.5 5 Favours fixed CPAP
Analysis 1.18. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 18 24-hour systolic BP.
Bloch 2018 113 126 (10.6) 95 127 (9.7) 55.26% -1[-3.77,1.77]
Pépin 2016 161 128.1 (14.2) 161 127.2 (14) 44.74% 0.9[-2.18,3.98]
Total *** 274 256 100% -0.15[-2.21,1.91]

Informed decisions.
Analysis 1.19. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 19 24-hour diastolic BP.
Bloch 2018 113 75 (10.6) 95 75 (9.7) 31.05% 0[-2.77,2.77]
Pépin 2016 161 78.1 (8) 161 76.8 (9) 68.95% 1.3[-0.56,3.16]
Total *** 274 256 100% 0.9[-0.65,2.44]

Analysis 1.20. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 20 Diurnal mean BP.
Bloch 2018 113 96 (10.6) 95 96 (9.7) 36.95% 0[-2.77,2.77]
Pépin 2016 161 98.4 (9.2) 161 97.4 (10.2) 63.05% 1[-1.12,3.12]
Total *** 274 256 100% 0.63[-1.05,2.32]

Analysis 1.21. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 21 Diurnal systolic BP.
Bloch 2018 113 132 (10.6) 95 133 (9.7) 56.63% -1[-3.77,1.77]
Pépin 2016 161 132.9 (14.4) 161 132.4 (14.6) 43.37% 0.5[-2.67,3.67]
Total *** 274 256 100% -0.35[-2.44,1.74]

Informed decisions.
Analysis 1.22. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 22 Diurnal diastolic BP.
Bloch 2018 113 78 (10.6) 95 78 (9.7) 35.24% 0[-2.77,2.77]
Pépin 2016 161 81.8 (8.9) 161 80.4 (9.8) 64.76% 1.4[-0.64,3.44]
Total *** 274 256 100% 0.91[-0.74,2.55]

Analysis 1.23. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 23 Nocturnal mean BP.
Bloch 2018 113 84 (10.6) 95 84 (9.7) 38.55% 0[-2.77,2.77]
Pépin 2016 161 87.6 (10) 161 86.9 (10.1) 61.45% 0.7[-1.5,2.9]
Total *** 274 256 100% 0.43[-1.29,2.15]

Analysis 1.24. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 24 Nocturnal systolic BP.
Bloch 2018 113 116 (10.6) 95 115 (19.5) 37.68% 1[-3.38,5.38]
Pépin 2016 161 119 (15.7) 161 118.2 (15.5) 62.32% 0.8[-2.61,4.21]
Total *** 274 256 100% 0.88[-1.81,3.57]

Heterogeneity: Tau2=0; Chi2=0, df=1(P=0.94); I2=0%
Analysis 1.25. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 25 Nocturnal diastolic BP.
Bloch 2018 113 68 (10.6) 95 68 (9.7) 33.47% 0[-2.77,2.77]
Pépin 2016 161 71.5 (8.9) 161 70.3 (9.1) 66.53% 1.2[-0.77,3.17]
Total *** 274 256 100% 0.8[-0.81,2.4]

Informed decisions.
Analysis 1.26. Comparison 1 Auto-CPAP versus fixed CPAP, Outcome 26 Tolerability outcomes.
Study or subgroup Auto-CPAP Fixed CPAP Odds Ratio Odds Ratio
1.26.1 Intolerable treatment pressure
Bloch 2018 42/91 41/80 0.82[0.45,1.49]
1.26.2 Mask leak

Bloch 2018 34/91 27/80 1.17[0.62,2.2]
1.26.3 Dry mouth

Bloch 2018 42/91 45/80 0.67[0.36,1.22]
1.26.4 Stuffy nose

Bloch 2018 28/91 25/80 0.98[0.51,1.87]

Outcome 27 Patient preference (auto-CPAP/not auto-CPAP).
Study or subgroup Auto-CPAP Not auto-CPAP Odds Ratio Odds Ratio
n/N n/N M-H, Random, 95% CI M-H, Random, 95% CI
d'Ortho 2000 15/25 10/25 2.25[0.73,6.98]
Galetke 2008 13/20 7/20 3.45[0.94,12.65]
Hussain 2004 1/10 9/10 0.01[0,0.23]
Jarvis 2006 9/20 11/20 0.67[0.19,2.33]
Marrone 2004 14/22 8/22 3.06[0.9,10.46]
Nolan 2007 13/29 16/29 0.66[0.23,1.86]
Noseda 2004 16/24 8/24 4[1.2,13.28]
Nussbaumer 2006 26/30 4/30 42.25[9.53,187.22]
Randerath 2001 35/47 12/47 8.51[3.37,21.5]
Rohling 2011 13/33 20/33 0.42[0.16,1.13]
Rostig 2003 18/30 12/30 2.25[0.8,6.32]
Senn 2003 4/29 25/29 0.03[0.01,0.11]
To 2008 9/41 32/41 0.08[0.03,0.23]
Vennelle 2010 69/181 131/181 0.24[0.15,0.37]
Not auto-CPAP pref 0.001 0.1 1 10 1000 auto-CPAP preferred
Comparison 2. Bi-PAP versus fixed CPAP

studies partici-
pants
1 Machine usage (hours/night) 4 268 Mean Difference (Fixed, 95% CI) 0.14 [-0.17, 0.45]
2 Symptoms (Epworth Sleepiness 4 226 Mean Difference (Fixed, 95% CI) -0.49 [-1.46, 0.48]
Scale)
Informed decisions.

studies partici-
pants
3 Withdrawals (parallel group tri- 3 261 Odds Ratio (M-H, Fixed, 95% CI) 0.55 [0.26, 1.17]
als/first arm cross-over trials)
4 Quality of life (Functional Out- 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
comes of Sleep Questionnaire)
5 Quality of life (Sleep Apnoea 1 Mean Difference (Fixed, 95% CI) Totals not selected
Quality of Life Index)
6 Quality of life (SF-36 question- 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
naire)
6.1 Physical health 1 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
6.2 Mental heath 1 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
7 Apnoea Hypopnoea Index 2 179 Mean Difference (Fixed, 95% CI) 1.36 [-6.92, 9.63]
(events/hr)
8 Patient preference - BiPAP/no 2 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
preference or CPAP
9 Tolerability outcomes 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
9.1 Dry mouth 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
9.2 Mask intolerance 1 Odds Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
10 Treatment comfort score 1 Mean Difference (Fixed, 95% CI) Totals not selected
Analysis 2.1. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).
Study or subgroup Bi-PAP Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
ference
Gay 2003 12 15 0 (0.61) 6.71% 0[-1.19,1.19]
Gulati 2015 28 0 0.5 (0.26) 36.88% 0.49[-0.02,1]
Masa 2015 71 80 0 (0.36) 19.23% 0[-0.71,0.71]
Reeves-Hoché 1995 26 36 -0.1 (0.259) 37.18% -0.1[-0.61,0.41]
Total (95% CI) 100% 0.14[-0.17,0.45]

Favours fixed CPAP -2 -1 0 1 2 Favours Bi-PAP
Informed decisions.
Analysis 2.2. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).
ference
Gay 2003 12 15 -0.2 (1.655) 8.96% -0.2[-3.44,3.04]
Gonzalez-Moro 2005 10 10 -0.7 (1.544) 10.29% -0.7[-3.73,2.33]
Gulati 2015 28 0 -0.5 (0.767) 41.7% -0.5[-2,1]
Masa 2015 71 80 -0.5 (0.793) 39.05% -0.5[-2.05,1.05]
Total (95% CI) 100% -0.49[-1.46,0.48]

Heterogeneity: Tau2=0; Chi2=0.05, df=3(P=1); I2=0%
Test for overall effect: Z=1(P=0.32)
Favours Bi-PAP -5 -2.5 0 2.5 5 Favours fixed CPAP
Analysis 2.3. Comparison 2 Bi-PAP versus fixed CPAP, Outcome

Study or subgroup Bi-level PAP Fixed CPAP Odds Ratio Weight Odds Ratio
Gay 2003 0/15 0/12 Not estimable
Masa 2015 7/71 11/80 48.19% 0.69[0.25,1.88]
Reeves-Hoché 1995 5/31 16/52 51.81% 0.43[0.14,1.33]
Total (95% CI) 117 144 100% 0.55[0.26,1.17]

Total events: 12 (Bi-level PAP), 27 (Fixed CPAP)
Favours Bi-level PAP 0.005 0.1 1 10 200 Favours fixed CPAP
Analysis 2.4. Comparison 2 Bi-PAP versus fixed CPAP, Outcome

Study or subgroup Bi-PAP Fixed CPAP Mean Difference Mean Difference
Masa 2015 71 4.3 (17) 80 5.1 (16) -0.8[-6.08,4.48]
Fixed CPAP better -5 -2.5 0 2.5 5 Bi PAP better
Analysis 2.5. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 5 Quality of life (Sleep Apnoea Quality of Life Index).
Study or subgroup Bi-PAP Fixed CPAP Mean Dif- Mean Difference Mean Difference
ference
Gulati 2015 28 0 0.4 (0.38) 0.4[-0.34,1.14]
Favours Bi-PAP -2 -1 0 1 2 Favours fixed CPAP
Informed decisions.
Analysis 2.6. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 6 Quality of life (SF-36 questionnaire).
Study or subgroup Bi PAP Fixed CPAP Mean Difference Mean Difference
2.6.1 Physical health
Masa 2015 71 1.8 (8.7) 80 1.2 (8.9) 0.6[-2.21,3.41]
2.6.2 Mental heath

Masa 2015 71 1.7 (14) 80 4.6 (12) -2.9[-7.09,1.29]
Fixed CPAP better -10 -5 0 5 10 Bi PAP better
Analysis 2.7. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 7 Apnoea Hypopnoea Index (events/hr).
ference
Gulati 2015 28 0 -2.9 (8) 27.84% -2.9[-18.58,12.78]
Masa 2015 71 80 3 (4.969) 72.16% 3[-6.74,12.74]
Total (95% CI) 100% 1.36[-6.92,9.63]

Favours Bi-PAP -20 -10 0 10 20 Favours fixed CPAP
Analysis 2.8. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 8 Patient preference - BiPAP/no preference or CPAP.
Study or subgroup Bi-level PAP Not bi-level PAP Odds Ratio Odds Ratio
Gulati 2015 15/28 13/28 1.33[0.47,3.81]
Muir 1998 6/16 10/16 0.36[0.09,1.51]
No pref/CPAP 0.005 0.1 1 10 200 Pref bi-level PAP
Analysis 2.9. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 9 Tolerability outcomes.
Study or subgroup Bi-PAP Fixed CPAP Odds Ratio Odds Ratio
2.9.1 Dry mouth
Masa 2015 3/71 6/80 0.54[0.13,2.26]
2.9.2 Mask intolerance

Masa 2015 8/71 8/80 1.14[0.41,3.22]
Favours Bi-PAP 0.01 0.1 1 10 100 Favours fixed CPAP
Informed decisions.
Analysis 2.10. Comparison 2 Bi-PAP versus fixed CPAP, Outcome 10 Treatment comfort score.
ference
Gulati 2015 28 0 9 (6.4) 9[-3.54,21.54]
Comparison 3. CPAPexp versus fixed CPAP

studies partici-
pants
2 Symptoms (Epworth Sleepiness Scale) 6 515 Mean Difference (Fixed, 95% CI) 0.17 [-0.26, 0.60]
4 Quality of life (Functional Outcomes of 1 Mean Difference (IV, Fixed, 95% Totals not selected
Sleep Questionnaire) CI)
5 Quality of life (SF-36 questionnaire) 1 Mean Difference (IV, Fixed, 95% Subtotals only
CI)
5.1 Physical functioning 1 76 Mean Difference (IV, Fixed, 95% 6.20 [-3.05, 15.45]
CI)
5.2 Role physical score 1 76 Mean Difference (IV, Fixed, 95% -9.5 [-25.38, 6.38]
CI)
5.3 Bodily pain score 1 76 Mean Difference (IV, Fixed, 95% 7.20 [-3.69, 18.09]
CI)
5.4 General health score 1 76 Mean Difference (IV, Fixed, 95% 1.0 [-8.05, 10.05]
CI)
5.5 Vitality 1 76 Mean Difference (IV, Fixed, 95% -2.5 [-11.38, 6.38]
CI)
5.6 Social functioning score 1 76 Mean Difference (IV, Fixed, 95% -8.30 [-17.87, 1.27]
CI)
5.7 Role emotional score 1 76 Mean Difference (IV, Fixed, 95% -7.30 [-21.83, 7.23]
CI)
5.8 Mental health score 1 76 Mean Difference (IV, Fixed, 95% 2.0 [-4.86, 8.86]
CI)
6 Apnoea Hypopnoea Index (events/hr) 5 342 Mean Difference (Fixed, 95% CI) 0.24 [-0.49, 0.96]
7 Pressure of CPAP treatment (cmH2O) 2 241 Mean Difference (IV, Fixed, 95% -0.05 [-0.63, 0.52]
CI)
Informed decisions.

studies partici-
pants
8 Treatment satisfaction score 1 Mean Difference (IV, Fixed, 95% Totals not selected
CI)
9 Treatment comfort score 1 Mean Difference (IV, Fixed, 95% Totals not selected
CI)
10 Treatment interface score 1 Mean Difference (IV, Fixed, 95% Totals not selected
CI)
11 Preference 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
Analysis 3.1. Comparison 3 CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).
Study or subgroup C-Flex PAP Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
ference
Bakker 2010 39 37 -0.1 (0.491) 4.69% -0.11[-1.07,0.85]
Dolan 2008 92 92 0.2 (0.149) 50.96% 0.18[-0.11,0.47]
Gfüllner 2007 18 0 -0 (0.51) 4.35% -0.01[-1.01,0.99]
Leidag 2008 30 0 -0 (0.339) 9.82% -0.05[-0.72,0.62]
Marshall 2008 9 10 1.7 (1.173) 0.82% 1.7[-0.6,4]
Modrak 2007 26 0 0.3 (0.755) 1.98% 0.3[-1.18,1.78]
Nilius 2006 25 26 -0.1 (1.5) 0.5% -0.1[-3.04,2.84]
Pépin 2009 83 82 0.1 (0.342) 9.66% 0.07[-0.6,0.74]
Wenzel 2007 20 20 0.2 (0.256) 17.22% 0.2[-0.3,0.7]
Total (95% CI) 100% 0.14[-0.07,0.35]

Favours fixed CPAP -5 -2.5 0 2.5 5 Favours CPAP exp
Analysis 3.2. Comparison 3 CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).
Study or subgroup Expir pres- Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
sure relief ference
Bakker 2010 39 37 0.5 (0.86) 6.43% 0.5[-1.19,2.19]
Dolan 2008 92 92 -0.3 (0.686) 10.12% -0.3[-1.64,1.04]
Marshall 2008 9 10 5 (2.256) 0.93% 5[0.58,9.42]
Nilius 2006 25 26 -0.3 (1.401) 2.43% -0.3[-3.05,2.45]
Pépin 2009 83 82 -0.2 (0.79) 7.63% -0.2[-1.75,1.35]
Wenzel 2007 20 0 0.2 (0.256) 72.46% 0.2[-0.3,0.7]
Total (95% CI) 100% 0.17[-0.26,0.6]

Favours pressure relief -5 -2.5 0 2.5 5 Favours fixed CPAP
Informed decisions.
Analysis 3.3. Comparison 3 CPAPexp versus fixed CPAP, Outcome

Study or subgroup C-Flex Fixed CPAP Odds Ratio Weight Odds Ratio
Bakker 2010 0/39 4/41 17.96% 0.11[0.01,2.03]
Pépin 2009 27/110 26/108 82.04% 1.03[0.55,1.91]
Total (95% CI) 149 149 100% 0.86[0.48,1.55]

Total events: 27 (C-Flex), 30 (Fixed CPAP)
Favours C-Flex 0.005 0.1 1 10 200 Favours CPAP
Analysis 3.4. Comparison 3 CPAPexp versus fixed CPAP, Outcome

Study or subgroup C Flex PAP Fixed CPAP Mean Difference Mean Difference
Bakker 2010 39 18.3 (1.9) 37 18.7 (1.4) -0.4[-1.15,0.35]
Fixed CPAP better -10 -5 0 5 10 C Flex PAP better
Analysis 3.5. Comparison 3 CPAPexp versus fixed CPAP, Outcome 5 Quality of life (SF-36 questionnaire).
Study or subgroup C Flex PAP Fixed CPAP Mean Difference Weight Mean Difference
3.5.1 Physical functioning
Bakker 2010 39 80.9 (18.3) 37 74.7 (22.5) 100% 6.2[-3.05,15.45]
Subtotal *** 39 37 100% 6.2[-3.05,15.45]
Heterogeneity: Not applicable
3.5.2 Role physical score

Bakker 2010 39 71.7 (39.1) 37 81.2 (31.3) 100% -9.5[-25.38,6.38]
Subtotal *** 39 37 100% -9.5[-25.38,6.38]
3.5.3 Bodily pain score

Bakker 2010 39 77.2 (22.9) 37 70 (25.4) 100% 7.2[-3.69,18.09]
Subtotal *** 39 37 100% 7.2[-3.69,18.09]
3.5.4 General health score

Bakker 2010 39 67.6 (21.8) 37 66.6 (18.4) 100% 1[-8.05,10.05]
Subtotal *** 39 37 100% 1[-8.05,10.05]
Fixed CPAP better -40 -20 0 20 40 C flex better
Informed decisions.
Study or subgroup C Flex PAP Fixed CPAP Mean Difference Weight Mean Difference
3.5.5 Vitality
Bakker 2010 39 61.7 (22.1) 37 64.2 (17.2) 100% -2.5[-11.38,6.38]
Subtotal *** 39 37 100% -2.5[-11.38,6.38]
3.5.6 Social functioning score

Bakker 2010 39 75.7 (25.5) 37 84 (16.3) 100% -8.3[-17.87,1.27]
Subtotal *** 39 37 100% -8.3[-17.87,1.27]
3.5.7 Role emotional score

Bakker 2010 39 78.7 (35.8) 37 86 (28.6) 100% -7.3[-21.83,7.23]
Subtotal *** 39 37 100% -7.3[-21.83,7.23]
Heterogeneity: Tau2=0; Chi2=0, df=0(P<0.0001); I2=100%
3.5.8 Mental health score

Bakker 2010 39 78.9 (17.3) 37 76.9 (13) 100% 2[-4.86,8.86]
Subtotal *** 39 37 100% 2[-4.86,8.86]
Fixed CPAP better -40 -20 0 20 40 C flex better
Analysis 3.6. Comparison 3 CPAPexp versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr).
Study or subgroup Expir pres- Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
sure relief ference
Bakker 2010 39 37 0 (0.552) 45.03% 0[-1.08,1.08]
Leidag 2008 30 0 0.8 (1.364) 7.37% 0.8[-1.87,3.47]
Nilius 2006 25 26 1.2 (1.44) 6.61% 1.2[-1.62,4.02]
Pépin 2009 83 82 0.6 (0.639) 33.55% 0.6[-0.65,1.85]
Wenzel 2007 20 0 -1.4 (1.357) 7.44% -1.4[-4.06,1.26]
Total (95% CI) 100% 0.24[-0.49,0.96]

Informed decisions.
Analysis 3.7. Comparison 3 CPAPexp versus fixed CPAP, Outcome 7 Pressure of CPAP treatment (cmH2O).
Study or subgroup C-Flex Fixed CPAP Mean Difference Weight Mean Difference
Bakker 2010 39 11.7 (3.7) 37 11.5 (2.7) 15.68% 0.2[-1.25,1.65]
Pépin 2009 83 10.6 (2.1) 82 10.7 (2) 84.32% -0.1[-0.73,0.53]
Total *** 122 119 100% -0.05[-0.63,0.52]

Favours C-Flex -2 -1 0 1 2 Favours CPAP
Analysis 3.8. Comparison 3 CPAPexp versus fixed CPAP, Outcome 8 Treatment satisfaction score.
Study or subgroup C-Flex PAP Fixed CPAP Mean Difference Mean Difference
Dolan 2008 72 81 (18) 70 74 (22) 7[0.38,13.62]
C-Flex PAP better -10 -5 0 5 10 Fixed CPAP better
Analysis 3.9. Comparison 3 CPAPexp versus fixed CPAP, Outcome 9 Treatment comfort score.
Dolan 2008 72 75 (21) 70 68 (23) 7[-0.25,14.25]
Fixed CPAP better -40 -20 0 20 40 CPAPexp better
Analysis 3.10. Comparison 3 CPAPexp versus fixed CPAP, Outcome 10 Treatment interface score.
Dolan 2008 72 66 (24) 70 57 (26) 9[0.76,17.24]
C-Flex PAP better -20 -10 0 10 20 Fixed CPAP better
Analysis 3.11. Comparison 3 CPAPexp versus fixed CPAP, Outcome 11 Preference.

Study or subgroup C-Flex PAP Not C-Flex Odds Ratio Odds Ratio
Leidag 2008 9/18 9/18 1[0.27,3.69]
Not C-Flex preferred 0.01 0.1 1 10 100 C-Flex preferred
Informed decisions.
Comparison 4. Heated humidification + fixed CPAP versus fixed CPAP alone

studies partici-
pants
1 Machine usage (hours/night) 6 277 Mean Difference (Fixed, 95% CI) 0.37 [0.10, 0.64]
2 Symptoms (Epworth Sleepiness Scale) 4 184 Mean Difference (Fixed, 95% CI) -0.34 [-0.93, 0.26]
4 Apnoea Hypopnoea Index (events/hr) 1 Mean Difference (Fixed, 95% CI) Totals not selected
5 Quality of life (SF-36 questionnaire) 2 124 Mean Difference (IV, Fixed, 95% CI) 0.11 [-6.97, 7.18]
6 Nasal symptoms (parallel group trials) 1 Odds Ratio (M-H, Fixed, 95% CI) Subtotals only
6.1 Runny nose 1 73 Odds Ratio (M-H, Fixed, 95% CI) 0.32 [0.09, 1.15]
6.2 Congested or blocked nose 1 73 Odds Ratio (M-H, Fixed, 95% CI) 0.19 [0.07, 0.51]
7 Nasal symptoms (parallel group trials) 2 Std. Mean Difference (IV, Fixed, Subtotals only
95% CI)
7.1 Dry nose 2 103 Std. Mean Difference (IV, Fixed, -0.38 [-0.78, 0.01]
95% CI)
7.2 Runny nose 2 103 Std. Mean Difference (IV, Fixed, -0.30 [-0.69, 0.09]
95% CI)
7.3 Blocked nose 2 103 Std. Mean Difference (IV, Fixed, -0.38 [-0.78, 0.01]
95% CI)
7.4 Bleeding nose 2 103 Std. Mean Difference (IV, Fixed, -0.45 [-0.99, 0.10]
95% CI)
8 Preference 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
Analysis 4.1. Comparison 4 Heated humidification + fixed CPAP

versus fixed CPAP alone, Outcome 1 Machine usage (hours/night).
Study or subgroup Humidi- No humid- Mean Dif- Mean Difference Weight Mean Difference
fication ification ference
Heiser 2010 22 27 0.4 (0.594) 5.38% 0.42[-0.75,1.59]
Neill 2003 37 0 0.4 (0.181) 57.97% 0.41[0.05,0.76]
Ruhle 2011 44 0 0.2 (0.64) 4.65% 0.2[-1.05,1.45]
Ryan 2009 39 34 0 (0.41) 11.33% 0[-0.8,0.8]
Soudorn 2016 20 0 0.6 (0.346) 15.88% 0.6[-0.08,1.28]
Worsnop 2010 25 29 0.2 (0.63) 4.79% 0.2[-1.04,1.44]
Total (95% CI) 100% 0.37[0.1,0.64]
No humidity better -5 -2.5 0 2.5 5 Humidity better
Informed decisions.
No humidity better -5 -2.5 0 2.5 5 Humidity better
Analysis 4.2. Comparison 4 Heated humidification + fixed CPAP versus

fixed CPAP alone, Outcome 2 Symptoms (Epworth Sleepiness Scale).
Neill 2003 37 0 -0.3 (0.335) 81.78% -0.3[-0.96,0.36]
Ryan 2009 39 34 -1 (1.288) 5.53% -1[-3.52,1.52]
Soudorn 2016 20 0 0 (1.312) 5.33% 0[-2.57,2.57]
Worsnop 2010 25 29 -0.5 (1.117) 7.35% -0.5[-2.69,1.69]
Total (95% CI) 100% -0.34[-0.93,0.26]

Humidity better -5 -2.5 0 2.5 5 No humidity better
Analysis 4.3. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP
alone, Outcome 3 Withdrawals (parallel group trials/first arm cross-over trials).
Study or subgroup Humidification No humid- Odds Ratio Weight Odds Ratio
ification
Heiser 2010 13/35 12/39 59.71% 1.33[0.51,3.49]
Ryan 2009 3/42 5/39 40.29% 0.52[0.12,2.35]
Worsnop 2010 0/25 0/29 Not estimable
Total (95% CI) 102 107 100% 1[0.45,2.24]

Total events: 16 (Humidification), 17 (No humidification)
Favours humidification 0.05 0.2 1 5 20 Favours no humidification

fixed CPAP alone, Outcome 4 Apnoea Hypopnoea Index (events/hr).
Study or subgroup CPAP+Hu- CPAP Mean Dif- Mean Difference Mean Difference
midification ference
Ruhle 2011 44 0 0.3 (0.637) 0.3[-0.95,1.55]
Humidity better -2 -1 0 1 2 No humidity better
Informed decisions.

fixed CPAP alone, Outcome 5 Quality of life (SF-36 questionnaire).
Study or subgroup Humidification No humidification Mean Difference Weight Mean Difference
Ryan 2009 36 64.2 (24.1) 34 69.5 (21) 44.81% -5.3[-15.88,5.27]
Worsnop 2010 25 76 (16) 29 71.5 (19.7) 55.19% 4.5[-5.03,14.03]
Total *** 61 63 100% 0.11[-6.97,7.18]

Favours no humidification -20 -10 0 10 20 Favours humidification

fixed CPAP alone, Outcome 6 Nasal symptoms (parallel group trials).
Study or subgroup Humidification No humid- Odds Ratio Weight Odds Ratio
ification
4.6.1 Runny nose
Ryan 2009 4/39 9/34 100% 0.32[0.09,1.15]
Subtotal (95% CI) 39 34 100% 0.32[0.09,1.15]
4.6.2 Congested or blocked nose

Ryan 2009 9/39 21/34 100% 0.19[0.07,0.51]
Subtotal (95% CI) 39 34 100% 0.19[0.07,0.51]
Humidity better 0.02 0.1 1 10 50 No humidity better

fixed CPAP alone, Outcome 7 Nasal symptoms (parallel group trials).
Study or subgroup Humidification No humidifcation Std. Mean Difference Weight Std. Mean Difference
4.7.1 Dry nose
Heiser 2010 22 2.1 (2.3) 27 2.4 (2) 48.63% -0.14[-0.7,0.43]
Worsnop 2010 25 8 (12) 29 24 (33) 51.37% -0.62[-1.17,-0.07]
Subtotal *** 47 56 100% -0.38[-0.78,0.01]
4.7.2 Runny nose

Heiser 2010 22 1 (0.5) 27 1.3 (1.4) 47.56% -0.27[-0.84,0.3]
Humidification better -2 -1 0 1 2 No humidification better
Informed decisions.
Study or subgroup Humidification No humidifcation Std. Mean Difference Weight Std. Mean Difference
Worsnop 2010 25 6 (17) 29 14 (29) 52.44% -0.33[-0.86,0.21]
Subtotal *** 47 56 100% -0.3[-0.69,0.09]
4.7.3 Blocked nose

Heiser 2010 22 1.9 (1.9) 27 2.3 (2.3) 48.4% -0.18[-0.75,0.38]
Worsnop 2010 25 6 (12) 29 18 (26) 51.6% -0.57[-1.12,-0.02]
Subtotal *** 47 56 100% -0.38[-0.78,0.01]
4.7.4 Bleeding nose

Heiser 2010 22 1 (0.7) 27 1 (0) Not estimable
Worsnop 2010 25 1 (2) 29 8 (21) 100% -0.45[-0.99,0.1]
Subtotal *** 47 56 100% -0.45[-0.99,0.1]
Humidification better -2 -1 0 1 2 No humidification better
Analysis 4.8. Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 8 Preference.
Study or subgroup Humidifcation No humidification Odds Ratio Odds Ratio
Neill 2003 19/37 18/37 1.11[0.45,2.77]
Pref not humidity 0.1 0.2 0.5 1 2 5 10 Pref humidity
Comparison 5. Auto-CPAPexp versus fixed CPAP

studies partici-
pants
2 Symptoms (Epworth Sleepiness 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
Scale)
3 Withdrawals (parallel group tri- 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
als/first arm cross-over trials)
4 Quality of life (Functional Out- 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
5 Apnoea Hypopnoea Index (events/ 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
hr)
6 Pressure of CPAP treatment 2 113 Mean Difference (Fixed, 95% CI) -0.92 [-1.77, -0.07]
(cmH2O)
Informed decisions.

studies partici-
pants
7 Systolic blood pressure 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
8 Diastolic blood pressure 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
Analysis 5.1. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).
Study or subgroup Experi- Control Mean Dif- Mean Difference Weight Mean Difference
mental ference
Kushida 2011 46 47 0 (0.371) 76.2% 0.04[-0.69,0.77]
Meurice 2009 20 0 0 (0.664) 23.8% 0[-1.3,1.3]
Total (95% CI) 100% 0.03[-0.6,0.67]

Heterogeneity: Tau2=0; Chi2=0, df=1(P=0.96); I2=0%
Favours CPAP -4 -2 0 2 4 Favous Auto-flex
Analysis 5.2. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).
Study or subgroup Experimental Control Mean Difference Mean Difference
Kushida 2011 46 6.9 (4.3) 47 7.9 (5.4) -0.94[-2.91,1.03]
A flex PAP better -5 -2.5 0 2.5 5 Fixed CPAP better
Analysis 5.3. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome

Study or subgroup Experimental Control Odds Ratio Odds Ratio
Kushida 2011 10/56 10/57 1.02[0.39,2.69]
A flex PAP better 0.01 0.1 1 10 100 Fixed CPAP better
Analysis 5.4. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome

Study or subgroup A flex PAP Fixed CPAP Mean Difference Mean Difference
Kushida 2011 46 17.1 (2.2) 46 16.7 (3.3) 0.37[-0.77,1.51]
Fixed CPAP better -2 -1 0 1 2 A flex PAP better
Informed decisions.
Analysis 5.5. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 5 Apnoea Hypopnoea Index (events/hr).
Kushida 2011 46 1.3 (2.9) 47 1 (1.3) 0.22[-0.7,1.14]
A flex PAP better -2 -1 0 1 2 Fixed CPAP better
Analysis 5.6. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 6 Pressure of CPAP treatment (cmH2O).
Study or subgroup A flex PAP Fixed CPAP Mean Dif- Mean Difference Weight Mean Difference
ference
Kushida 2011 46 47 -0.8 (0.555) 61.02% -0.8[-1.89,0.29]
Meurice 2009 20 0 -1.1 (0.695) 38.98% -1.1[-2.46,0.26]
Total (95% CI) 100% -0.92[-1.77,-0.07]

A flex PAP lower -2 -1 0 1 2 Fixed CPAP lower
Analysis 5.7. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 7 Systolic blood pressure.
Kushida 2011 46 127.5 (13.4) 47 130.2 (14.9) -2.7[-8.46,3.06]
A flex PAP lower -10 -5 0 5 10 Fixed CPAP lower
Analysis 5.8. Comparison 5 Auto-CPAPexp versus fixed CPAP, Outcome 8 Diastolic blood pressure.
Kushida 2011 46 78.4 (9.4) 47 80.6 (9.6) -2.2[-6.06,1.66]
A flex PAP lower -5 -2.5 0 2.5 5 Fixed CPAP lower
Comparison 6. Bi-PAPexp versus fixed CPAP

studies partici-
pants
1 Machine usage (hours/night) 1 Mean Difference (Fixed, 95% CI) Totals not select-
ed
2 Number of participants who used CPAP 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not select-
therapy > 4 hours per night ed
Informed decisions.

studies partici-
pants
3 Quality of life (Functional Outcomes of 1 Mean Difference (IV, Fixed, 95% CI) Totals not select-
Sleep Questionnaire) ed
Analysis 6.1. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).
ference
Ballard 2007 51 53 0.8 (0.422) 0.8[-0.03,1.63]
Analysis 6.2. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome 2

Number of participants who used CPAP therapy > 4 hours per night.
Ballard 2007 25/51 15/53 2.44[1.08,5.48]
CPAP better 0.1 0.2 0.5 1 2 5 10 Bi-PAP better
Analysis 6.3. Comparison 6 Bi-PAPexp versus fixed CPAP, Outcome

Ballard 2007 46 1.5 (4.5) 43 0.5 (4.4) 1[-0.86,2.86]
Fixed CPAP better -5 -2.5 0 2.5 5 Bi-PAP better
Comparison 7. Auto Bi-PAP versus fixed CPAP

studies partici-
pants
1 Machine usage (hours/night) 2 Mean Difference (Fixed, 95% CI) -0.00 [-0.70, 0.70]
2 Number of participants who used 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected
CPAP therapy > trialist defined threshold
3 Symptoms (Epworth Sleepiness Scale) 2 Mean Difference (Fixed, 95% CI) 0.97 [-0.56, 2.51]
4 Withdrawals 2 83 Odds Ratio (M-H, Fixed, 95% CI) 2.41 [0.33, 17.43]
Informed decisions.

studies partici-
pants
5 Quality of life (Functional Outcomes of 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
Sleep Questionnaire)
6 Apnoea Hypopnoea Index (events/hr) 1 Mean Difference (Fixed, 95% CI) Totals not selected
Analysis 7.1. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).
ference
Blau 2012 15 17 -0.3 (0.457) 61.34% -0.3[-1.2,0.6]
Powell 2012 26 22 0.5 (0.576) 38.66% 0.47[-0.66,1.6]
Total (95% CI) 100% -0[-0.7,0.7]

Analysis 7.2. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 2

Number of participants who used CPAP therapy > trialist defined threshold.
Powell 2012 16/26 12/22 1.33[0.42,4.22]
CPAP better 0.01 0.1 1 10 100 Bi-PAP better
Analysis 7.3. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 3 Symptoms (Epworth Sleepiness Scale).
ference
Blau 2012 15 17 0.8 (1.035) 57.25% 0.8[-1.23,2.83]
Powell 2012 26 22 1.2 (1.198) 42.75% 1.2[-1.15,3.55]
Total (95% CI) 100% 0.97[-0.56,2.51]

Informed decisions.
Analysis 7.4. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 4 Withdrawals.
Study or subgroup Auto bi-PAP Fixed CPAP Odds Ratio Weight Odds Ratio
Blau 2012 2/17 1/18 62.7% 2.27[0.19,27.58]
Powell 2012 1/26 0/22 37.3% 2.65[0.1,68.3]
Total (95% CI) 43 40 100% 2.41[0.33,17.43]

Total events: 3 (Auto bi-PAP), 1 (Fixed CPAP)
Favours auto bi-PAP 0.01 0.1 1 10 100 Favours fixed CPAP
Analysis 7.5. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome

Powell 2012 25 100 (11.3) 22 100.1 (15.4) -0.1[-7.91,7.71]
Fixed CPAP better -20 -10 0 10 20 Bi-PAP better
Analysis 7.6. Comparison 7 Auto Bi-PAP versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr).
ference
Blau 2012 15 17 -1.8 (1.617) -1.8[-4.97,1.37]
Comparison 8. CPAPexp with wakefulness detection versus fixed CPAP

studies partici-
pants
1 Machine usage (hours/night) 1 Mean Difference (Fixed, 95% CI) Totals not selected
2 Symptoms (Epworth Sleepiness 1 Mean Difference (Fixed, 95% CI) Totals not selected
Scale)
3 Quality of life (Functional Out- 1 Mean Difference (Fixed, 95% CI) Totals not selected
4 Apnoea Hypopnoea Index 1 Mean Difference (Fixed, 95% CI) Totals not selected
(events/hr)
5 Mask leak 1 Mean Difference (Fixed, 95% CI) Totals not selected
Informed decisions.
Analysis 8.1. Comparison 8 CPAPexp with wakefulness detection

versus fixed CPAP, Outcome 1 Machine usage (hours/night).
Study or subgroup CPAP expira- Fixed CPAP Mean Dif- Mean Difference Mean Difference
tory relief ference
Bogan 2017 61 0 -0.3 (0.206) -0.27[-0.68,0.13]
Favours fixed CPAP -2 -1 0 1 2 Favours CPAPexp

versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).
Study or subgroup Expir pres- Fixed CPAP Mean Dif- Mean Difference Mean Difference
sure relief ference
Bogan 2017 65 0 0.5 (0.383) 0.5[-0.25,1.25]
Favours pressure relief -2 -1 0 1 2 Favours fixed CPAP
Analysis 8.3. Comparison 8 CPAPexp with wakefulness detection versus fixed

CPAP, Outcome 3 Quality of life (Functional Outcomes of Sleep Questionnaire).
Study or subgroup CPAP expira- Fixed CPAP Mean Dif- Mean Difference Mean Difference
tory pressure ference
Bogan 2017 62 0 -1.8 (0.87) -1.8[-3.51,-0.09]
Favours fixed CPAP -5 -2.5 0 2.5 5 Favours CPAPexp

versus fixed CPAP, Outcome 4 Apnoea Hypopnoea Index (events/hr).
Study or subgroup Expir pres- Fixed CPAP Mean Dif- Mean Difference Mean Difference
sure relief ference
Bogan 2017 61 0 1.6 (0.536) 1.6[0.55,2.65]
Analysis 8.5. Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 5 Mask leak.
Study or subgroup CPAPexp Fixed CPAP Mean Dif- Mean Difference Mean Difference
ference
Bogan 2017 62 0 -4.9 (2.168) -4.9[-9.15,-0.65]
Favours CPAPexp -10 -5 0 5 10 Favours fixed CPAP
Informed decisions.
ADDITIONAL TABLES
Table 1. Table of devices

Device Mechanism
Fixed CPAP A single pressure is set. The device attempts to maintain this during inspiration and expiration and
throughout the period of use.
Automatically adjusting-CPAP High and low pressure limits are set. The device adjusts its pressure within these limits to try to
(auto-CPAP) maintain a patent (clear and open) airway. The pressure does not vary between inspiration and ex-
piration but will vary across the period of use.
Bilevel positive airway pres- Two pressure levels are set. The device aims to co-ordinate with patient breaths to deliver the high-
sure (Bi-PAP) er pressure throughout inspiration and the lower pressure throughout expiration. If the patient has
no respiratory effort some machines will produce timed or back up breaths.
CPAP with expiratory pressure A basic pressure is set for the period of use. The device tracks patient effort and drops from the ba-
relief (CPAPexp) sic pressure by a preset amount at the start of expiration, increasing back to the basic pressure at
the end of expiration. The pressure drops by 1 of 3 amounts selected according to patient comfort.
Heated humidification The addition of heated humidification to the CPAP circuit increases the humidity and temperature
of inspired air; this aims to reduce dryness of the upper respiratory tract and improve comfort.
Auto-CPAPexp This device combines the modalities of automatically adjusting continuous positive airway pres-
sure and expiratory pressure relief.
Bi-PAPexp This device combines the modalities of bilevel positive airway pressure and expiratory pressure re-
lief.
Auto bi-PAP with pressure re- This device reduces the pressure delivered at the end of inspiration and pressure during the early
lief part of expiration, combined with an automatic titration modality.
CPAPexp with wakefulness de- This CPAP device with expiratory pressure relief incorporates a sensor to detect when the user is
tection rousing from sleep.
Table 2. Summary of study and participant characteristics at baseline
Intervention arm No. of studies (par- Average Average Age % Male par- Average BMI Average AHI Average ESS
ticipants) study dura- ticipants (kg/m2) (events/hr)
Library
Cochrane
tion (weeks)
Auto-CPAP 36 (2135) 11 52 71 34 42 13
Bi-PAP 6 (325) 16 55 76 35 50 13
Better health.
Informed decisions.
Trusted evidence.
CPAPexp 10 (658) 8 53 60 34 54 13
Humidification + fixed CPAP 6 (359) 7 52 74 32 42 12
Auto-CPAPexp 2 (188) 14 49 77 34 39 11
Bi-PAP (multimodality) 3 (187) 12 54 86 32 41 10
CPAPexp with wakefulness detection 1 (70) 4 51 69 36 - 11
All interventions are compared with fixed CPAP. AHI: Apnoea Hypopnoea Index; BMI: body mass index; ESS: Epworth Sleepiness Scale. Averages calculated as mean of baseline
means from studies contributing to each comparison. For cross-over studies duration reflects amount of time treatment groups are exposed to one of the treatment arms, rather
than the entire length of the study (conventionally double the duration of a single treatment arm exposure).

176
Informed decisions.
APPENDICES
Appendix 1. Sources and search methods for the Cochrane Airways Trials Register
Electronic searches: core databases
Database Dates searched Frequency of search
CENTRAL (via the Cochrane Register of Studies (CRS)) From inception Monthly
MEDLINE (Ovid) 1946 onwards Weekly
EMBASE (Ovid) 1974 onwards Weekly
PsycINFO (Ovid) 1967 onwards Monthly
CINAHL (EBSCO) 1937 onwards Monthly
AMED (EBSCO) From inception Monthly
Handsearches: core respiratory conference abstracts
Conference Years searched
American Academy of Allergy, Asthma and Immunology (AAAAI) 2001 onwards
American Thoracic Society (ATS) 2001 onwards
Asia Pacific Society of Respirology (APSR) 2004 onwards
British Thoracic Society Winter Meeting (BTS) 2000 onwards
Chest Meeting 2003 onwards
European Respiratory Society (ERS) 1992, 1994, 2000 onwards
International Primary Care Respiratory Group Congress (IPCRG) 2002 onwards
Thoracic Society of Australia and New Zealand (TSANZ) 1999 onwards
MEDLINE search strategy used to identify trials for the Cochrane Airways Trials Register
Sleep apnoea search
1. exp Sleep Apnea Syndromes/
2. (sleep$ adj3 (apnoea$ or apnoea$)).mp.
3. (hypopnea$ or hypopnoea$).mp.
4. OSA.mp.
5. SHS.mp.
Informed decisions.
6. OSAHS.mp.
7. or/1-6
Filter to identify RCTs

1. exp "clinical trial [publication type]"/
2. (randomized or randomised).ab,ti.
3. placebo.ab,ti.
4. dt.fs.
5. randomly.ab,ti.
6. trial.ab,ti.
7. groups.ab,ti.
8. or/1-7
9. Animals/
10. Humans/
11. 9 not (9 and 10)
12. 8 not 11
The MEDLINE strategy and RCT filter are adapted to identify trials in other electronic databases
Appendix 2. Search strategy to identify trials from the Cochrane Airways Trials Register
Database platform: Cochrane Register of Studies
Dates covered: September 2008 to October 2018
#1 SLP:MISC2
#2 MeSH DESCRIPTOR Sleep Apnea, Obstructive
#3 sleep near3 (apnoea* or apnoea*)
#4 (hypopnea* or hypopnoea*)
#5 (OSA OR SHS OR OSAHS:TI,AB)
#6 (#1 OR #2 OR #3 OR #4 OR #5)
#7 humidif*
#8 CPAP
#9 autopap
#10 Auto* NEXT CPAP
#11 APAP
#12 NCPAP
#13 PPR
#14 C* NEXT Flex
#15 positive* NEAR3 pressure*
#16 "expiratory pressure"
#17 PEEP
#18 IPB
#19 IPPB
#20 (continuous* OR nasal* OR inspiratory*) AND "positive airway"
#21 #7 or #8 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20
#22 (#6 and #21)
[Note: in search line #1, MISC1 refers to the field in the record where the reference has been coded for condition, in this case, sleep apnoea)
Search strategy used for September 2008 version

Dates covered: all years to September 2008
All records in the Specialised Register coded as 'sleep apnoea' were searched using the following terms:
Informed decisions.
(Humidif* OR CPAP OR Auto-CPAP OR APAP OR NCPAP OR PPR OR C-Flex OR"positive pressure" OR positive-pressure OR "expiratory
pressure" OR PEEP OR IPB OR IPPB) OR (continuous OR nasal OR inspiratory AND ("positive airway*"))
Appendix 3. Average machine usage data
Study Screened Entered Com- % % En- Mean hours

pleted Screened tered used (con-
trol group)
Bakker 2010 751 80 76 10.1 95 5.2
Ballard 2007 204 104 104 51 100 2.9
Berry 2014 240 156 131 54.5 84 4
Blau 2012 Not reported 35 32 N/A 91 5.6
Bloch 2018 952 208 172 18 82 5.5
Bogan 2017 Not reported 70 65 N/A N/A 4.81
Castronovo 2006 Not reported 50 40 N/A 80 Not reported
Chang 2015 Not reported 25 19 N/A 76 5.8
d'Ortho 2000 Not reported 25 25 N/A 100 4.7
Damjanovic 2009 Not reported 100 78 N/A 78 5.1
Dolan 2008 222 184 142 64 76 5.3
Ficker 2003 Not reported 100 95 N/A 95 4.8
Fietze 2007 Not reported 21 21 N/A 100 4.2
Galetke 2008 Not reported 20 20 NA 100 6.4
Gay 2003 Not reported 40 27 N/A 67.5 5.6
Gfüllner 2007 Not reported Not reported 18 N/A N/A 5.3
Gonzalez-Moro 2005 Not reported 20 Not re- N/A N/A Not reported
ported
Gulati 2015 75 31 28 37.3 90.3 2.2
Heiser 2010 Not reported 75 49 N/A 65.3 4.3
Hudgel 2000 Not reported 53 39 N/A 73.6 5.5
Hukins 2004 58 55 46 79 84 4.86
Hussain 2004 Not reported 10 (as- 10 N/A 100 3.7

sumed)
Jarvis 2006 Not reported Not reported 20 N/A N/A 6.8
Informed decisions.
(Continued)
Kendrick 2002 Not reported 41 27 N/A 65.85 Not reported
Konermann 1998 Not reported 50 48 N/A 96 5.6
Kushida 2011 178 168 140 78.7 83.3 4.6
Leidag 2008 Not reported 30 18 N/A 60 5.8
Loube 2004 Not reported Not reported Not re- N/A N/A Not reported
ported
Marrone 2004 Not reported 22 (as- 22 N/A 100 4.4

sumed)
Marshall 2008 Not reported Not reported 19 N/A NA 3
Masa 2015 351 221 (num- 200 57% 90% 5.3

bers report-
ed here re-
flect par-
ticipants
screened for
three treat-
ment arms)
Massie 2003 Not reported 46 44 N/A 95.6 4.5
Meurice 1996 Not reported 16 16 N/A 100 5.7
Modrak 2007 Not reported Not reported 26 N/A N/A 5.1
Muir 1998 Not reported Not reported 16 N/A N/A 4.9
Neill 2003 Not reported 42 37 N/A 88 5.3
Nilius 2006 Not reported 52 51 N/A 98 5.2
Nolan 2007 Not reported 34 29 N/A 85 4.9
Noseda 2004 93 27 24 26 89 5.3 (aver-

age usage
on 'effective
nights')
Nussbaumer 2006 Not reported 34 30 N/A 88 4.8
Patruno 2007 Not reported 40 31 N/A 78 6.1
Pépin 2009 Not reported 20 20 N/A 100 5.3
Pépin 2016 569 322 281 49.4 87.3 5.2
Powell 2012 51 48 47 92.2 97.9 4.4
Informed decisions.
(Continued)
Randerath 2001 Not reported 52 47 N/A 90 5.3
Reeves-Hoché 1995 Not reported 83 62 N/A 75 5
Resta 2004 Not reported 20 20 N/A 100 5.3
Rochford 2006 Not reported N/A 13 N/A N/A 4.6
Rohling 2011 Not reported 39 33 N/A 84.6 6.6
Rostig 2003 Not reported 30 30 (as- N/A 100 (as- 3.8

sumed) sumed)
Ruhle 2011 Not reported 44 44 N/A 100 4.5
Ryan 2009 125 125 112 91 91 5.21
Senn 2003 Not reported 31 29 N/A 93.55 7.1
Sériès 1997 39 36 36 92.3 100 Not reported
Sériès 2001 Not reported 48 48 (as- N/A 100 (as- 4.2

sumed) sumed)
Soudorn 2016 104 20 20 19.2 19.2 5.2
Teschler 2000 Not reported 10 10 N/A 100 6.1
To 2008 Not reported 43 41 N/A 95 3.8
Vennelle 2010 368 200 181 49.1 90.5 4
Wenzel 2007 Not reported 20 (as- 20 NA 100 (as- 5.8

sumed) sumed)
West 2006 633 98 86 16 88 5.6
Worsnop 2010 Not reported 54 54 (as- N/A 100 (as- 4.5

sumed) sumed)
Abbreviations: N/A: not applicable
WHAT'S NEW
Date Event Description
15 October 2018 New search has been performed Search run and 21 studies included. 2 studies previously includ-
ed are now excluded. 4 studies are ongoing and one completed
study is awaiting classification pending fuller details of methods
and results.
15 October 2018 New citation required and conclusions Additional evidence has increased certainty in previous findings.
have changed New data on blood pressure have been included.
Informed decisions.

We updated the methods to reflect current Cochrane standards
e.g. adding a 'Summary of findings' table and PRISMA diagram.
HISTORY
Protocol first published: Issue 3, 2001
Review first published: Issue 4, 2004
10 September 2008 New citation required and conclusions Review split; 28 trials added to review; new data available for pri-
have changed mary outcomes. The main findings of the original review have
been strengthened with the new data. A consistent difference in
favour of auto-titrating CPAP machines has been identified from
cross-over studies, although the estimate from parallel group
trials includes no difference. Alternative pressure modification
methods such as C-Flex, bi-level pressure and additional humidi-
fication require more research.
4 September 2008 New search has been performed Literature search re-run
9 April 2008 Amended Converted to new review format
29 December 2006 New citation required and conclusions Substantive amendment

have changed
CONTRIBUTIONS OF AUTHORS
BK (2019 update): study assessment, data collection and entry, write up (results section, development of discussion and conclusion
sections).
TJL: study assessment, data collection and entry, write up (results section, development of discussion and conclusion sections, abstract
and plain language summary).
DRW: study assessment, data collection and entry, development of results, discussion and conclusion
IS: protocol development, development of results, discussion and conclusions.
Contributions of editorial team

Rebecca Fortescue (Co-ordinating Editor): edited the review; advised on methodology, interpretation and content; approved the final
review prior to publication.
Chris Cates (Co-ordinating Editor, Contact Editor) checked the data entry prior to the full write up of the review; advised on methodology,
interpretation and content.
Emma Dennett (Managing Editor): co-ordinated the editorial process; advised on interpretation and content; edited the review.
Emma Jackson (Assistant Managing Editor): conducted peer review; edited the plain language summary and reference sections of the
protocol and the review.
Elizabeth Stovold (Information Specialist): designed the search strategy; ran the searches; edited the search methods section.
DECLARATIONS OF INTEREST
Barry Kennedy: none known
Toby Lasserson is employed by Cochrane.
Dariusz Wozniak: none known
Informed decisions.
Ian Smith is an investigator on the Gulati 2015 study. Since the 2009 version of the review he has not had involvement in the assessment
of bias or certainty of evidence. Recevied payments for lectures from UCB Pharma, this company markets medication for sleep disorders,
but none relevant to this review.
SOURCES OF SUPPORT
Internal sources
• Papworth Hospital NHS Trust, UK.
• St George's, University of London, UK.
External sources
• The authors declare that no such funding was received for this systematic review, Other.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

For the 2019 update of the review we have identified the following additional comparisons of interest.
1. Automatically adjusting CPAP with expiratory pressure relief (auto-CPAPexp) versus fixed CPAP
2. Automatically adjusting bilevel positive airway pressure (auto bi-PAP) versus fixed CPAP.
3. CPAP with expiratory pressure relief (CPAPexp) with wakefulness detection versus fixed CPAP.
We decided to exclude studies recruiting people with positional sleep apnoea since the pressure requirement would differ from those with
non-positional obstructive sleep apnoea (OSA).
We removed oxygen saturation (SaO2) and Respiratory Disturbance Index (RDI) as outcomes in favour of blood pressure parameters and
AHI which were commonly reported and more directly addressed the objectives of our review.
We removed the risk of domain relating to monitored usage based on peer review comments for the 2019 update of the review. This is likely
to be an ethical requirement in most settings where the studies were conducted and does not feature as a domain in Cochrane standards
or guidance.
We applied GRADE to the findings in this review and added in remaining domains for risk of bias relating to selective other reporting and
other bias.
We combined data from parallel and cross-over studies. Having reconsidered the studies in this review, we took the view that both parallel
and cross-over studies address the same question of interest in this review with regard to machine use, symptoms, objective measures
of sleep disturbance and quality of life. Data on withdrawals and adverse events have been collected from parallel studies and combined
only with data from the first arm of cross-over studies, where this could be used.
Subgroup analysis
We have not conducted any subgroup analysis due to the limited amount of statistical variation overall. Our prespecified subgroups were:
1. population - male versus female;

2. baseline AHI > 20 versus < 20 per hour;
3. study quality - high versus low (based upon the allocation concealment scores);
4. previous usage of CPAP.
Sensitivity analyses
We decided not to assess the impact of auto-CPAP delivered by forced oscillation technique as part of a sensitivity analysis for the 2019
update. This was done due to the very limited number of studies using this technique.
We did not carry out the sensitivity analysis looking at awareness of monitoring. Following peer review comments received on the 2019
update of the review we have come to regard this as a feature of obtaining consent during recruitment to the studies, and not study
design per se. We did not carry out a sensitivity analysis because we could not satisfactorily identify a subset of studies at low risk of
bias. The multiple sources of bias across domains led us to downgrade the certainty of evidence (See Summary of findings for the main
comparison).
We removed the threshold I2 for proceeding with a sensitivity analysis for random-effects modelling. On reflection, we felt that it was
better to focus on the number of studies rather than the amount of variation as the basis for exploring model choice since random-effects
modelling assumes a distribution of true, related effects. We thought that this assumption is more reasonable as the number of studies
increased, irrespective of the statistical heterogeneity.
Informed decisions.
INDEX TERMS
Medical Subject Headings (MeSH)

*Continuous Positive Airway Pressure [methods]; *Humidifiers; Outcome Assessment, Health Care; Quality of Life; Randomized
Controlled Trials as Topic; Sleep Apnea, Obstructive [*therapy]
MeSH check words

Adult; Humans

Pressure modification or humidification for improving usage ofcontinuous positive airway pressure machines in adults withobstructive sleep apnoea (Review)

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Pressure modification or humidification for improving usage ofcontinuous positive airway pressure machines in adults withobstructive sleep apnoea (Review)

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Cochrane

Pressure modification or humidification for improving usage of

Kennedy B, Lasserson TJ, Wozniak DR, Smith I

Kennedy B, Lasserson TJ, Wozniak DR, Smith I.

Pressure modification or humidification for improving usage of

Barry Kennedy1a, Toby J Lasserson2b, Dariusz R Wozniak3, Ian Smith3

Editorial group: Cochrane Airways Group.

Data collection and analysis

PLAIN LANGUAGE SUMMARY

What is the aim of this review?

What was studied in this review?

What are the main results of the review?

This Plain Language Summary is current to October 2018

Patient or population: adults with a diagnosis of OSA

Outcomes Anticipated absolute effects* (95% CI) Relative № of Certain- Com-

Number of participants using ma- Study population OR 1.16 346 ⊕⊕⊝⊝

Cochrane Database of Systematic Reviews

Withdrawals (parallel group tri- Study population OR 0.90 1275 ⊕⊕⊕⊝

Blood pressure (mmHg) Systolic blood pressure - 353 ⊕⊕⊕⊝

Diastolic blood pressure - 353 ⊕⊕⊝⊝

Cochrane Database of Systematic Reviews

Patient or population: adults with a diagnosis of sleep apnoea

Cochrane Database of Systematic Reviews

Withdrawals (parallel group tri- Study population OR 0.55 261 ⊕⊕⊝⊝

Cochrane Database of Systematic Reviews

Blood pressure - not measured - - - - -

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

Patient or population: adults with a diagnosis of sleep apnoea

Follow-up: range 2 to 24 weeks

Machine usage assessed by number of - - - - -

Withdrawals (parallel group trials/first Study population OR 0.86 298 ⊕⊕⊝⊝

Cochrane Database of Systematic Reviews

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

Patient or population: adults with a diagnosis of sleep apnoea

Follow-up: range 3 weeks to 12 weeks

assessed by number of participants using machine for 4 or more

Symptoms The mean symp- MD 0.34 ESS lower - 184 ⊕⊕⊝⊝

Quality of life assessed with FOSQ: scale from 5 to 20 - - - - -

Cochrane Database of Systematic Reviews

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

BACKGROUND Pressure modification devices adjust airway pressure according to

METHODS Data for this outcome could be measured as mean differences

3. Australian New Zealand Clinical Trials Registry Unit of analysis issues

Measures of treatment effect Subgroup analysis and investigation of heterogeneity

Figure 1. Study flow diagram: review update

Top up searches in June 2019 identified 202 records, of which we Interventions

Blinding Other potential sources of bias

Sleep disruption Adverse events

There was a high degree of statistical variation in the size and

Nasal blockage Mask leak

Secondary outcomes events/hour, 95% CI -6.92 to 9.63; 2 studies; 179 participants;

CPAPexp may be used more than fixed CPAP although the CI

Secondary outcomes Short-Form 36 (SF-36)

Withdrawals Apnoea Hypopnoea Index (AHI)

Secondary outcomes Quality of life scores

Symptom scores Short-Form 36 (SF-36)

AHI was measured in one small study of four weeks duration (N =

Adverse events DISCUSSION

Bironneau V, Loustonneau E, Pontier S, Gagnadoux F, Iamandi I, NCT03428516 {published data only}

Garvey 2015 sleep apnea. Sleep Disorders 2017;2017:2760650. [DOI:

Law 2009 Patel 2018