Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea

Barry Kennedy; Toby J Lasserson; Dariusz R Wozniak; Ian Smith

doi:10.1002/14651858.CD003531.pub4

. 2019 Dec 2;2019(12):CD003531. doi: 10.1002/14651858.CD003531.pub4

Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea

Barry Kennedy ^1,^✉, Toby J Lasserson ², Dariusz R Wozniak ³, Ian Smith ³

Editor: Cochrane Airways Group

PMCID: PMC6888022 PMID: 31792939

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.

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.

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

Summary of findings

Background

Description of the condition

Obstructive sleep apnoea (OSA) arises from recurrent episodes of pharyngeal collapse during sleep. It disrupts sleep architecture, ventilation and cardiovascular homeostasis (Eckert 2008; Kasai 2012). As these episodes recur over time, adults with OSA experience fragmented and poor quality sleep. They report excessive daytime sleepiness, mood alterations as well as impaired cognition and memory (Gagnon 2014; Karimi 2015). Repetitive hypoxaemia is associated with increased risk of cardiovascular and cerebrovascular events (Shahar 2001; Yaggi 2005; Young 2008; Redline 2010; Drager 2011). OSA frequently coexists with systemic hypertension and, in some people, contributes to its development (Konecny 2014; Pépin 2014). Other consequences of untreated OSA include increased risk of motor vehicle accidents, higher prevalence of depression and reduced productivity at work (Tregear 2009; Jordan 2014; Hirsch Allen 2015; Karimi 2015; BaHammam 2016).

Description of the intervention

The main treatment of choice for OSA is continuous positive airway pressure (CPAP). CPAP devices apply positive pressure to the upper airway and prevent pharyngeal collapse. Consistent use of CPAP improves physiological parameters of sleep, reduces daytime sleepiness, enhances cognition and reduces motor vehicle accidents (Giles 2006; Karimi 2015). Adults with OSA are advised to use CPAP for a minimum of four hours per night; research indicates that four hours is the threshold at which symptoms of daytime sleepiness resolve (Weaver 2007).

Longitudinal studies also indicate that CPAP lowers the cardiovascular burden of OSA in people who are compliant with it (Doherty 2005; Marin 2005; Martínez‐García 2012; Myhill 2012). However, evidence from randomised studies of a beneficial effect of CPAP on cardiovascular outcomes is weak. This may be partly related to low adherence to CPAP in these studies; in the majority of randomised controlled trials (RCTs) included in a recent meta‐analysis, the average CPAP usage was < 4 hours/night (McEvoy 2016; Yu 2017). Early seminal studies had indicated that people who use CPAP for at least four hours per night obtain symptomatic benefit and, subsequently, this threshold was accepted in research studies and clinical practice as a threshold likely to meet a key goal of therapy (Kribbs 1993; Engleman 1994; Reeves Hoche 1994).

Despite the benefits associated with treatment, usage of CPAP is often low. Estimates of people who use CPAP regularly in the long term vary, but range between 29% and 85% (Pépin 1999; Weaver 2010; Rotenberg 2016; Libman 2017). Tolerating treatment with CPAP is a highly complex issue and determined by a number of factors. Disease severity, symptom relief from CPAP, underlying neurological disease or nasal anatomy play a role alongside psychological factors, such as locus of control, anxiety and depression (Wild 2004; Broström 2010a; Catcheside 2010). Finally, device‐related factors such as mask leak, skin abrasions and nasal congestion may deter use (Bollig 2010; Wickwire 2013).

Making the CPAP device more comfortable to use could also increase compliance. This could be achieved by varying the delivered airway pressure at the point of inhalation and exhalation, or by humidifying the CPAP circuit.

Pressure modification devices adjust airway pressure according to changes in airway resistance or the respiratory cycle. Automatically adjusting positive airway pressure (auto‐CPAP), bilevel positive airway pressure (bi‐PAP) or CPAP with expiratory pressure relief (CPAPexp) are modalities of pressure modification. Auto‐CPAP devices analyse inspiratory flow and titrate the airway pressure accordingly to maintain a constant airflow; thus, when airway resistance decreases (i.e. sleeping in lateral position or after weight loss), these devices reduce the pressure applied to the airway. In bi‐PAP devices, a higher pressure is applied to the airway throughout the inspiratory phase and a lower pressure is applied throughout expiration. In CPAPexp there is a decrease in airway pressure for a portion of the expiratory phase (Ryden 2014; Brown 2017; Freedman 2017).

Manufacturers have also combined multiple modalities of pressure modification into a single device e.g. auto‐CPAP combined with expiratory relief or bi‐PAP with an automatic titration mechanism (auto‐CPAP combined with bi‐PAP). These multimodality devices may have additive benefits on comfort compared to single modality devices.

Humidification devices humidify the air that is delivered to the upper airway through the CPAP circuit.

How the intervention might work

Pressure modification interventions are designed to vary and achieve the necessary pressure to maintain airway patency through the night. This has the potential to deliver the same effect on sleep disruption and symptoms but at a lower treatment pressure. By this mechanism of action, a reduction in mean pressure could minimise local side effects of CPAP, improve tolerance and increase associated usage. Bi‐PAP and C‐Flex are also designed to lower expiratory pressure and reduce the expiratory work of breathing, thereby increasing comfort. Adding humidification to the delivery of pressure in the airway might decrease side effects in the upper airway due to cold, dry airflow. Rather than change the pressure, humidity makes the pressured air delivered to the airway less likely to cause dry mouth or throat, which could improve the tolerability of CPAP. Table 5 outlines the details of each device and its associated mechanism.

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 (auto‐CPAP)	High and low pressure limits are set. The device adjusts its pressure within these limits to try to maintain a patent (clear and open) airway. The pressure does not vary between inspiration and expiration but will vary across the period of use.
Bilevel positive airway pressure (Bi‐PAP)	Two pressure levels are set. The device aims to co‐ordinate with patient breaths to deliver the higher 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 relief (CPAPexp)	A basic pressure is set for the period of use. The device tracks patient effort and drops from the basic 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 pressure and expiratory pressure relief.
Bi‐PAPexp	This device combines the modalities of bilevel positive airway pressure and expiratory pressure relief.
Auto bi‐PAP with pressure relief	This device reduces the pressure delivered at the end of inspiration and pressure during the early part of expiration, combined with an automatic titration modality.
CPAPexp with wakefulness detection	This CPAP device with expiratory pressure relief incorporates a sensor to detect when the user is rousing from sleep.

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Why it is important to do this review

The prevalence and economic costs of OSA are likely to increase as levels of obesity increase globally (Peppard 2013; Garvey 2015; Sanna 2018). Establishing the evidence base for different types of positive pressure therapy devices will help to inform decisions aimed at reducing the health burden of poorly treated OSA. Cognitive behavioural therapy, education and increasing engagement between the patient and CPAP provider have recently been shown to increase machine use (Wozniak 2014). The last version of this review was published in 2009 (Smith 2009a), and we decided to update the review in light of a number of studies that have been published since we last assessed the evidence in this area.

Objectives

To determine the effects of positive pressure modification or humidification on increasing CPAP machine usage in adults with OSA.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) of either parallel group or cross‐over design. We included blinded and unblinded studies.

Types of participants

We included trials involving adults of either sex with a diagnosis of obstructive sleep apnoea (OSA), based on history and results of sleep studies. The sleep studies were either oximetry studies showing desaturation index (DI) of at least 5 per hour or of respiratory movements and airflow to give an Apnoea Hypopnoea Index (AHI) of at least 5 per hour.

We excluded trials assessing interventions in people with central sleep apnoea and where sleep apnoea was related to sleeping position.

Types of interventions

We included the following comparisons.

Automatically adjusting CPAP continuous positive airway pressure (auto‐CPAP) including forced oscillation technique versus fixed pressure setting CPAP (fixed CPAP).
Bilevel positive airway pressure (Bi‐PAP) versus fixed CPAP.
Continuous positive airway pressure with expiratory pressure relief (CPAPexp) versus fixed CPAP.
Heated humidification plus fixed CPAP versus fixed CPAP alone.
Automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp) versus fixed CPAP.
Bi‐PAP with expiratory pressure relief (Bi‐PAPexp) versus fixed CPAP
Automatically adjusting Bi‐PAP (auto Bi‐PAP) versus fixed CPAP.
CPAPexp with wakefulness detection versus fixed CPAP.

We excluded studies that were conducted as short‐term laboratory‐based interventions, since they did not intend to capture the effects of interventions administered on a nightly basis at home. We excluded studies that were less than two weeks in duration because we were primarily interested in the effects of pressure modification in the context of ongoing use of CPAP.

The effects of educational and behavioural interventions are now considered in a different review (Wozniak 2014).

Types of outcome measures

Primary outcomes

Usage of CPAP, measured as initial acceptance, where data were available, and subsequent usage as measured by:

counter output that records the cumulative time that power is turned on to a CPAP machine (this does not provide information on actual time of day and duration of CPAP used each 24‐hour period);
microprocessor and monitor that measures the pressure at the mask;
subjective participant reports of the duration of CPAP use.

Data for this outcome could be measured as mean differences (MDs) in hourly use per participant per night or as the number of participants who used machines for more than four hours per night.

Secondary outcomes

Symptom scores (such as the Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS) and nasal symptoms)
Withdrawals
Quality of life or Health Status (such as the Functional Outcomes of Sleep Questionnaire (FOSQ) and Sleep Apnoea Quality of Life Index (SAQLI) scores. We analysed data from the Short‐Form 36 (SF‐36) but we did not use it as the basis for the 'Summary of findings' tables)
Sleep disruption outcomes (Apnoea Hypopnoea Index (AHI) and arousals)
Treatment pressure (for auto‐CPAP)
Blood pressure outcomes
Adverse events (most commonly measured as tolerability of treatment pressure, mask leak and nasal or oral symptoms)
Expression of preference (from cross‐over studies)

For the comparison of humidification and CPAP versus CPAP alone, we considered nasal symptoms as an additional outcome. This was intended to capture the effects of humidity directly where the mechanism of action is targeted.

Search methods for identification of studies

Electronic searches

The previously published version of this review included searches up to September 2008 (Smith 2009a). The search period for this update is September 2008 to October 2018.

We identified studies from Cochrane Airways Trials Register (Cochrane Airways 2019), which is maintained by the Information Specialist for the Group. The Cochrane Airways Trials Register contains studies identified from several sources:

monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), through the Cochrane Register of Studie (CRS);
weekly searches of MEDLINE Ovid SP 1946 to date;
weekly searches of Embase Ovid SP 1974 to date;
monthly searches of PsycINFO Ovid SP 1967 to date;
monthly searches of CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature) 1937 to date;
handsearches of the proceedings of major respiratory conferences.

Studies contained in the Trials Register are identified through search strategies based on the scope of Cochrane Airways. Details of these strategies, as well as a list of handsearched conference proceedings are in Appendix 1. See Appendix 2 for the search strategy used to identify studies for this review.

We also searched the following trials registries.

US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov)
World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch)
Australian New Zealand Clinical Trials Registry (www.anzctr.org.au)

We searched the Cochrane Airways Trials Register and trials registries to 15 October 2018, with no restriction on type or language of publication.

Searching other resources

We reviewed reference lists of all primary studies and review articles for additional references. We contacted authors of identified trials to identify other published and unpublished studies. We checked for errata or retractions of included studies published in full text on PubMed on 8 April 2019.

Data collection and analysis

Selection of studies

Two review authors independently reviewed titles, abstracts and citations identified through electronic searching to assess potential relevance for full review. We obtained articles deemed to be of potential relevance for the review. Following scrutiny of full text, two authors independently assessed studies for inclusion based on the criteria for population, intervention, study design and outcomes (BK and DW or TL). We measured agreement by simple consensus. We resolved disagreement by involving a third party.

Data extraction and management

Two review authors extracted data from published and unpublished studies independently (BK and DW or TL). We made attempts to contact study investigators to confirm data where necessary and to provide clarification for additional information for the review.

Assessment of risk of bias in included studies

Two review authors (BK and TL) assessed the risk of bias of the included studies in terms of the process of allocation of participants to treatment groups (sequence generation and allocation concealment), blinding in relation to objective and subjective outcomes (judged as performance bias and detection bias), subsequent impact of missing data on the analysis, selective outcome reporting and other sources of bias.

We judged the studies to be at low, unclear or high risk of bias and provide supporting statements from the trial reports or correspondence, as necessary.

Measures of treatment effect

We calculated mean differences (MDs) for continuous variables measured on identical metrics for parallel and cross‐over studies. We used standardised mean differences (SMDs) to combine data from studies using different scales to measure the same outcome. For one outcome we noted that variants of the Functional Outcomes of Sleep Questionnaire (FOSQ) were used in two studies (Analysis 2.4) and so we used SMDs to combine data. We report continuous data from meta‐analyses as MDs or SMDs with 95% confidence intervals (CIs).

2.4 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep Questionnaire).

For dichotomous outcomes, we calculated an odds ratio (OR) based upon the number of participants with an event versus the number of participants without an event.

Unit of analysis issues

We entered data from cross‐over studies as generic inverse variance (GIV) outcome that were either adjusted for the within‐person design or we back‐calculated the standard error (SE) from exact P 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, we used treatment group means and standard deviations (SDs) as if from parallel group trials.

One parallel study assessed the effects of four different auto‐CPAP machines compared with a device delivering fixed CPAP. We aggregated the data from the four treatment groups and used this in our analyses (Meurice 2007).

In the forest plots we have displayed sample sizes from cross‐over studies differently to parallel group studies. To generate correct total sample sizes we have entered the total sample size to the intervention arm and 0 to the corresponding control group column. This is for display purposes only and does not affect the estimated treatment effect or the error for the study.

Dealing with missing data

Where data pertaining to mean CPAP machine usage were not available from the trial reports, we contacted study authors to determine whether data could be obtained directly. We elected to impute SDs for one parallel group study for the primary outcome. We generated a simple average of the SDs for other studies because data were only reported as medians and 25th and 75th centiles.

Assessment of heterogeneity

We assessed the level of statistical variation with the I² statistic and P value for the Chi² test (Higgins 2003).

Assessment of reporting biases

We inspected publication bias visually to check for possible asymmetry for outcomes included in the 'Summary of findings' table with more than 10 studies.

Data synthesis

We combined data from studies where we judged the population, interventions and definition of outcomes to be similar, using a fixed‐effect model. We conducted a sensitivity analysis by using random‐effects modelling to determine whether variation between the studies affected the pooled estimate.

Subgroup analysis and investigation of heterogeneity

In the absence of any statistical heterogeneity for the outcomes of usage and symptoms under the comparison of auto‐CPAP and fixed CPAP, and the limited number of studies available for other outcomes, we decided not to carry out any subgroup analysis (see Differences between protocol and review for details on planned subgroups). We will reconsider our planned subgroups in future versions of the review should data become available that allows us to assess the impact of gender or baseline AHI on the outcomes of interest.

Sensitivity analysis

We could not carry out our planned sensitivity analysis to assess the risk of bias (see Differences between protocol and review). We did include the following sensitivity analyses for outcomes relevant to the 'Summary of findings' table.

We applied random‐effects modelling to assess the sensitivity of our results to the choice of statistical model. We applied this sensitivity analysis to outcomes where we had sufficient number of studies to use as the basis for an assumed distribution of effects (5 or more).
For the outcome of average machine usage we decided to include data from a large parallel group study which presented data as medians and ranges instead of means and SDs (Pépin 2016). As a sensitivity analysis, we included this study by assuming the medians to equate to means, and assigned SDs based on an average of other parallel studies.

Rating the certainty of evidence

We rated the certainty of evidence for key outcomes as high, moderate, low or very low using GRADE methods, as outlined in the GRADE Handbook (Schünemann 2013). We based these ratings on consideration of how risk of bias, inconsistency, imprecision, indirectness and publication bias impact on the findings of outcomes most relevant to decision making.

We have prioritised the comparison of auto‐CPAP and fixed CPAP over others as the basis of the conclusions of the review, but have included three other comparisons in the 'Summary of findings' tables (bi‐PAP, humidification and CPAP with expiratory pressure relief) as they are commonly used alternatives to either fixed CPAP or auto‐CPAP. The outcomes we have prioritised are based on relevance for decision making and were taken for the following latest available time points.

Average machine usage (measured as nightly average use per participant and as the number of participants achieving more than 4 hours usage per night).
Symptoms, measured by ESS.
Withdrawals.
Quality of life, measured by FOSQ.
AHI (mean number of events per hour).
Blood pressure.
Adverse events (measured by tolerability of machines).

In the text of the review we have preferentially focused reporting of follow‐up on these outcomes, where possible.

Results

Description of studies

Results of the search

See Figure 1 for the study flow diagram for searches between 2009 and 15 October 2018. From 1566 records, 64 references describing 48 potentially eligible studies were assessed for eligibility. We excluded 22 studies and included 21 studies. With the studies already included from previous searches, 64 studies met the eligibility criteria of the review. There are four ongoing studies and one completed study is awaiting assessment.

Top up searches in June 2019 identified 202 records, of which we retrieved 10 for further scrutiny. Five records reported secondary analyses from one of the included studies (Masa 2015), and one referred to an excluded study (Pradeepan 2017). We also identified the published protocol for one ongoing study (NCT03428516) and conference abstract for a large completed study (NCT02749812). We assigned two records to 'Studies awaiting classification' (see below).

Included studies

Study design

Thirty studies have parallel groups and 33 have a cross‐over design. In one trial (Loube 2004), the description of methods was insufficient to determine whether the study was a parallel or cross‐over study.

Participants

The studies recruited 3922 participants who had been diagnosed with sleep apnoea and had little exposure to continuous positive airway pressure (CPAP) before study entry. The populations had similar characteristics across the seven comparisons considered by this review (Table 6). The proportion of male participants was high and ranged from 60% to 86% for the comparisons in the review. The average age of the study populations ranged between 49 and 55 and average body mass index (BMI) was between 32 kg/m² and 35 kg/m². Baseline sleep disruption, as measured by the Apnoea Hypopnoea Index (AHI) was severe and Epworth Sleepiness Scale (ESS) scores indicated that the study populations had excessive daytime sleepiness (11 to 16). One study recruited people with coexisting sleep apnoea and obesity hypoventilation syndrome (Masa 2015).

2. Summary of study and participant characteristics at baseline.

Intervention arm	No. of studies (participants)	Average study duration (weeks)	Average Age	% Male participants	Average BMI (kg/m²)	Average AHI (events/hr)	Average ESS
Auto‐CPAP	36 (2135)	11	52	71	34	42	13
Bi‐PAP	6 (325)	16	55	76	35	50	13
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

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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).

The majority of studies excluded participants who had previously used CPAP (58/64). Of the six studies actively recruiting existing users of CPAP, Jarvis 2006 included people who were established on CPAP therapy. In four studies participants were eligible if they had used CPAP but were deemed to be infrequent users (Muir 1998; Rostig 2003; Powell 2012; Gulati 2015).

Two auto‐CPAP studies selected participants who required high treatment pressure to correct sleep disturbance (Massie 2003; Noseda 2004).

Most studies were conducted in Europe and North America. A smaller number of trials were conducted in Australia (Hudgel 2000; Teschler 2000; Worsnop 2010; Hukins 2004; Jarvis 2006; Rochford 2006), Hong Kong (To 2008; Chang 2015), New Zealand (Neill 2003; Marshall 2008; Bakker 2010), and Thailand (Soudorn 2016).

The median study sample size is 40 (range 10 to 322).

Interventions

Average study duration was between 12 and 16 weeks in studies comparing auto‐CPAP, auto‐CPAPexp or bi‐PAP with fixed CPAP. Studies comparing CPAPexp or additional humidification with fixed CPAP had shorter average durations (8 and 6 weeks, respectively).

The use of standard CPAP titration protocols was common across the studies. Most were conducted over one or two nights, with the exception of Pépin 2016, where home‐based pressure titration occurred over eight nights. Extended adaptation protocols which increased the exposure of participants to CPAP devices were undertaken in two studies in order to establish optimal CPAP pressure and comfort prior to formal initiation of treatment (e.g. Senn 2003; Bloch 2018). This was used by Dolan 2008 to exclude participants who used CPAP for less than four hours per night during run‐in and by Ballard 2007 to identify and recruit people who averaged less than four hours per night to participate in the randomised phase of the study.

Automatically adjusting CPAP (auto‐CPAP)

Thirty‐six studies (2135 participants) compared auto‐CPAP with fixed CPAP (Meurice 1996; Sériès 1997; Konermann 1998; d'Ortho 2000; Hudgel 2000; Teschler 2000; Randerath 2001; Sériès 2001; Ficker 2003; Kendrick 2002; Massie 2003; Nolan 2007; Rostig 2003; Senn 2003; Hukins 2004; Hussain 2004; Marrone 2004; Noseda 2004; Resta 2004; Castronovo 2006; Jarvis 2006; Nussbaumer 2006; Rochford 2006; To 2008; West 2006; Fietze 2007; Meurice 2007; Patruno 2007; Galetke 2008; Damjanovic 2009; Vennelle 2010; Rohling 2011; Pépin 2016; Berry 2014; Chang 2015; Bloch 2018). Treatment pressures ranged from 6.2 to 10.6 in the fixed CPAP groups and were lower in the auto‐CPAP groups by about 1 cm H₂O.

Bilevel positive airway pressure (Bi‐PAP)

Six studies (325 participants) compared bi‐PAP machines (excluding those with automatically adjusting and expiratory pressure mode) with fixed CPAP (Reeves‐Hoché 1995; Muir 1998; Gay 2003; Gonzalez‐Moro 2005; Gulati 2015; Masa 2015).

CPAP with expiratory pressure relief (CPAPexp)

Ten studies (658 participants) compared CPAP with expiratory pressure relief with fixed CPAP (Loube 2004; Dolan 2008; Marshall 2008; Nilius 2006; Gfüllner 2007; Modrak 2007; Wenzel 2007; Leidag 2008; Pépin 2009; Bakker 2010).

Heated humidification plus fixed CPAP

Six studies (359 participants) compared the addition of humidification to fixed CPAP with fixed CPAP (Neill 2003; Worsnop 2010; Ruhle 2011; Ryan 2009; Heiser 2010; Soudorn 2016). There was no humidification in the control groups.

Multimodality devices

Automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp)

Two studies (188 participants) compared auto‐CPAPexp with fixed CPAP (Meurice 2009; Kushida 2011).

Bi‐PAP with expiratory pressure relief (Bi‐PAPexp) and auto Bi‐PAPexp

One study in 104 participants compared Bi‐PAPexp with fixed CPAP (Ballard 2007). Two studies evaluated auto Bi‐PAPexp with fixed CPAP (Blau 2012; Powell 2012).

CPAPexp with wakefulness detection

One study of 70 participants looked at CPAP with an expiratory pressure device that responded to the detection of wakefulness and compared it with fixed CPAP (Bogan 2017).

Outcomes

Availabilty of outcome data for our primary outcome of machine usage was high. We were able to obtain data for machine usage as either continuous or dichotomous data for 89% of studies (57/64). Symptoms measured with ESS and sleep disturbance measured with AHI were reported in 66% and 56% of studies respectively. Of 29 studies providing data on treatment pressure (45%), 24 compared auto‐CPAP with fixed CPAP.

Quality of life was reported in 23 studies (36%). Two instruments validated in sleep apnoea research were used in 11 studies (Sleep Apnoea Quality of Life Index (SAQLI) and Functional Outcomes of Sleep Questionnaire (FOSQ)) either in combination with the Short‐Form 36 (SF‐36) or on their own. For the remaining studies, only the SF‐36 was used.

There was considerable variation in the methods used to measure tolerability or adverse events in 23 studies (36%). Studies used diary records and interviews to capture effects as both dichotomous data (did or did not experience the event) or scales to rate problems with mask leak, pressure tolerance, dry mouth and nasal symptoms. Variation in how this was done prevented us from combining data in a meta‐analysis for many comparisons of interest. A number of cross‐over studies reported unadjusted dichotomous data and we could not account for this approach in our analysis due to the requirement for individual participant data.

Excluded studies

We excluded 133 studies after retrieving the full text because they did not meet the eligibility criteria of the review. Reasons for their exclusion are detailed in the 'Characteristics of excluded studies' table. On re‐examining two previously included studies against the review eligibility criteria, we determined that one of them was too short to be considered eligible for inclusion since they exposed participants to one week of treatment in a cross‐over study (Torvaldsson 2003), and the other used humidification with auto‐CPAP (Salgado 2006).

Studies awaiting classification

One study recruiting 800 participants comparing auto‐CPAP with fixed CPAP completed in 2015, but a conference abstract from 2018, reports some results (NCT02749812). Following correspondence with the study investigators we are not anticipating full availability of the results from this study before 2020. One study of a humidification device (Boyer 2019), and a secondary analysis of a CPAP compliance trial (Zamora 2019), are awaiting classification and we will determine their eligibility for future versions of the review.

Ongoing studies

Six studies are listed as ongoing. We have not been able to determine whether interim results from two studies presented as conference abstracts have been superseded by reports of completed studies (Morton 2001; Ventateswaren 2003). One published protocol pertains to a study in rescue workers who developed OSA subsequent to the collapse of the World Trade Centre in New York, USA in 2001 (NCT01753999). Two small studies evaluate auto‐CPAP (ACTRN12618000379213p; NCT01753999), and one is assessing a device that delivers pressure to the upper airway through one nostril at a time (ACTRN12617001090303).

Risk of bias in included studies

An overview of the study level judgements is provided in Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Allocation

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 bias domain only (Marrone 2004). For the remaining studies, one or both domains were at unclear risk of bias.

Blinding

We judged that the open‐label or single‐blind design used in many of the studies would likely have had a greater impact on usage outcomes, withdrawal and subjectively reported outcomes than on AHI, treatment pressure and blood pressure (see Figure 2). Measures to reduce the risk of bias arising from study personnel and participants becoming aware of treatment group assignment resulted in low risk of bias for subjective outcomes in 21 studies, a high risk of bias in 29 studies and unclear for the remainder. We judged objective outcomes to be at low risk of performance bias in 53 studies. Our 'Risk of bias' judgements for outcome assessment followed closely those we made for performance bias, given that participants would have been rating symptoms and quality of life.

Incomplete outcome data

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 where loss to follow‐up was low enough to not affect the outcomes of interest (very limited and balanced attrition or where all study participants completed). We noted that risk of attrition affected cross‐over and parallel group studies in different ways. A number of cross‐over participants who withdrew and did not cross over to the second arm of the trial were excluded from the analysis. Withdrawals for a number of long‐term parallel group studies meant that loss to follow‐up affected the long‐term outcome measurements. Twenty‐two studies had a high risk of bias and we judged the remainder as unclear.

Selective reporting

Where trial registry records have been available for a study we have been able to cross‐check prespecified outcomes against what was reported. We found evidence of selective outcome reporting for 'Summary of findings' table outcomes in seven studies (Gay 2003; Fietze 2007; Patruno 2007; Meurice 2009; Heiser 2010; Vennelle 2010; Powell 2012). The impact of this selective reporting on the overall results was limited.

Other potential sources of bias

We could not find any reason to consider the studies at high risk of other sources of bias. We could not reliably assess this domain in 11 studies, only available as conference abstracts, and judged them to be at unclear risk of bias.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4

Summary of findings for the main comparison. Auto‐CPAP compared to fixed CPAP for sleep apnoea in adults.

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  Comparison: fixed CPAP
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Average effect or risk with fixed CPAP	Average effect or risk with auto‐CPAP
Average machine usage (hours per night) Median follow‐up: 6 weeks	Average nightly machine usage 5 hours per night across all CPAP arms	0.21 hours per person per night longer  (0.11 longer to 0.31 longer) The average effect is about 13 minutes longer per person per night (6 minutes to 20 minutes)	‐	1452  (31 RCTs)	⊕⊕⊕⊝  Moderate¹
Number of participants using machine for 4 or more hours per night Follow‐up: range 3 to 16 weeks	Study population		OR 1.16 (0.75 to 1.81)	346 (2 RCTs)	⊕⊕⊝⊝  Low^1,2
	601 per 1000	636 per 1000 (530 to 732)
Symptoms assessed with ESS from 0 to 24 Median follow‐up: 6 weeks	Average symptom scores ranged from 4.1 to 8.6 on the ESS	0.44 ESS units lower  (0.72 lower to 0.16 lower)	‐	1285  (25 RCTs)	⊕⊕⊕⊝  Moderate¹	MCID of between 2 to 3 has been proposed by Patel 2018.
Withdrawals (parallel group trials/first arm cross‐over trials) Median follow‐up: 6 weeks	Study population		OR 0.90  (0.64 to 1.27)	1275  (13 RCTs)	⊕⊕⊕⊝  Moderate ²
	110 per 1000	100 per 1000  (74 to 136)
Quality of life assessed with FOSQ scale from 5 to 20 Follow‐up: range 4 to 104 weeks	The mean quality of life score was 5.58 on the FOSQ	0.12 FOSQ units higher  (0.21 lower to 0.46 higher)	‐	352  (3 RCTs)	⊕⊕⊝⊝  Low^1,3	MCID for FOSQ has not been confirmed; a change of 1 unit has been proposed as representing a possible meaningful change (Billings 2014).
AHI measured by number of events/hr Median follow‐up: 6 weeks	Average AHI ranged from 2 to 9 events per hour	0.48 events per hour higher  (0.16 higher to 0.80 higher)	‐	1256  (26 RCTs)	⊕⊕⊕⊕  High ⁴
Blood pressure (mmHg) Follow‐up 12 and 16 weeks	Systolic blood pressure		‐	353  (2 RCTs)	⊕⊕⊕⊝  Moderate ⁵
	The mean systolic blood pressure was 133 mmHg	1.87 mmHg higher  (1.08 lower to 4.82 higher)
	Diastolic blood pressure		‐	353  (2 RCTs)	⊕⊕⊝⊝  Low ⁶
	The mean diastolic blood pressure was 78 mmHg	2.92 mmHg higher  (1.06 higher to 4.77 higher)
Adverse events (machine tolerability outcomes) Follow‐up: 4 to 36 weeks	Nine studies provided information on tolerability outcomes, but data could not be combined because they were measured and analysed inconsistently across the studies. 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.		‐	574  (9 RCTs)	⊕⊝⊝⊝  Very low ⁷
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; 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.
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.

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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  Comparison: fixed CPAP
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with fixed CPAP	Risk with Bi‐PAP	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Machine usage (hours/night) Follow‐up: 4 to 52 weeks	Average nightly machine usage 5.5 hours per night across CPAP	0.14 hours/night higher  (0.17 lower to 0.45 higher)	‐	268  (4 RCTs)	⊕⊕⊝⊝  Low ^{1 2}
Machine usage assessed by number of participants using machine for 4 or more hours per night ‐ not measured	‐	‐	‐	‐	‐
Symptoms assessed with ESS from 0 to 24 Follow‐up: 4 to 12 weeks	The mean symptoms ranged from 8 to 11 ESS units	0.49 ESS units lower (1.46 lower to 0.48 higher)	‐	226  (4 RCTs)	⊕⊕⊝⊝  Low ^{1 3}	MCID of between 2 to 3 has been proposed by Patel 2018.
Withdrawals (parallel group trials/first arm cross‐over trials) Follow‐up: 4 to 52 weeks	Study population		OR 0.55  (0.26 to 1.17)	261  (3 RCTs)	⊕⊕⊝⊝  Low ^{3 4}
	188 per 1000	113 per 1000 (57 to 213)	OR 0.55  (0.26 to 1.17)	261  (3 RCTs)	⊕⊕⊝⊝  Low ^{3 4}
Quality of life assessed with FOSQ: scale from 5 to 20 Follow‐up: 8 weeks	Mean change from baseline 5.1 units	0.8 FOSQ units lower (6.08 lower to 4.48 units higher)	‐	151 (1 RCT)	⊕⊕⊝⊝  Low ^{3 5}	MCID for FOSQ has not been confirmed; a change of 1 unit has been proposed as representing a possible meaningful change (Billings 2014).
AHI measured with number of events/hr Follow‐up: 4 to 8 weeks	The mean AHI was 6.6 events/hour	1.36 events/hour lower  (6.92 lower to 9.63 higher)	‐	179  (2 RCTs)	⊕⊕⊝⊝  Low ⁶
Blood pressure ‐ not measured	‐	‐	‐	‐	‐
Adverse events (machine tolerability outcomes) Follow‐up: 4 to 52 weeks	Five studies provided information on tolerability outcomes but data could not be combined because they were measured and analysed inconsistently across the studies. 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 intolerance (11% and 10%) in Bi‐PAP and CPAP groups, respectively. Two small studies (N = 46) reported non‐specific adverse events. One reported that 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 versus fixed CPAP 60, P = 0.16).		‐	239  (5 RCTs)	⊕⊝⊝⊝  Very low ^{1 7}
*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
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.

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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
Patient or population: adults with a diagnosis of sleep apnoea  Setting: Europe, USA, New Zealand  Intervention: CPAP with expiratory pressure relief  Comparison: fixed CPAP
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with fixed CPAP	Risk with CPAP with expiratory pressure relief	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Machine usage  assessed by hours/night Follow‐up: range 2 to 24 weeks	The mean machine usage was 5.1 hours/night	MD 0.14 hours/night higher  (0.07 lower to 0.35 higher)	‐	609  (9 RCTs)	⊕⊕⊝⊝  Low ^{1 2}
Machine usage assessed by number of participants using machine for 4 or more hours per night ‐ not measured	‐	‐	‐	‐	‐
Symptoms  assessed with ESS Follow‐up: range 4 to 24 weeks	The mean symptoms was 7 ESS	0.17 ESS units higher  (0.26 lower to 0.60 higher)	‐	515  (6 RCTs)	⊕⊕⊕⊝  Moderate ¹	MCID of between 2 to 3 has been proposed by Patel 2018.
Withdrawals (parallel group trials/first arm cross‐over trials) Follow‐up: 12 weeks	Study population		OR 0.86  (0.48 to 1.55)	298  (2 RCTs)	⊕⊕⊝⊝  Low ³
	201 per 1000	178 per 1000  (108 to 281)	OR 0.86  (0.48 to 1.55)	298  (2 RCTs)	⊕⊕⊝⊝  Low ³
Quality of life assessed with FOSQ: scale from 5 to 20 Follow‐up: 12 weeks	The mean quality of life was 18.7 FOSQ units	0.4 FOSQ units lower  (1.15 lower to 0.35 higher)	‐	74  (1 RCT)	⊕⊕⊝⊝  Low ⁴	MCID for FOSQ has not been confirmed; a change of 1 unit has been proposed as representing a possible meaningful change (Billings 2014).
AHI measured by number of events/hr Follow‐up: range 6 to 12 weeks	The mean AHI was 5.3 events/hour	0.24 events/hour higher  (0.49 lower to 0.96 higher)	‐	342  (5 RCTs)	⊕⊕⊕⊕  High
Blood pressure ‐ not measured	‐	‐	‐	‐	‐
Adverse events (machine tolerability outcomes) Follow‐up: range 4 to 24 weeks	No specific measures of nasal or oral symptoms were carried out in six studies providing information on tolerability outcomes. Four studies assessed treatment comfort scores but data could not be combined. 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.		‐	577 (6 RCTs)	⊕⊝⊝⊝  Very low ^{5 6}
*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; CI: confidence interval; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep Questionnaire; MCID: minimal clinically important difference; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial.
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.

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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.

⁶Downgraded 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
Patient or population: adults with a diagnosis of sleep apnoea  Setting: Europe, Australia, New Zealand and Thailand  Intervention: heated humidification + fixed CPAP  Comparison: fixed CPAP alone
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with fixed CPAP alone	Risk with heated humidification + fixed CPAP
Machine usage  assessed by hours per night Follow‐up: range 3 weeks to 12 weeks	The mean machine usage was 5 hours	MD 0.37 hours higher  (0.10 higher to 0.64 higher)	‐	277  (6 RCTs)	⊕⊕⊝⊝  Low ^{1 2}
Machine usage assessed by number of participants using machine for 4 or more hours per night ‐ not measured	‐	‐	‐	‐	‐
Symptoms  assessed with ESS Follow‐up: range 3 weeks to 12 weeks	The mean symptoms ranged from 4 to 9 ESS	MD 0.34 ESS lower  (0.93 lower to 0.26 higher)	‐	184  (4 RCTs)	⊕⊕⊝⊝  Low ^{3 4}
Withdrawals (parallel group trials/first arm cross‐over trials) Follow‐up: median 12 weeks	Study population		OR 1.00  (0.45 to 2.24)	316  (3 RCTs)	⊕⊝⊝⊝  Very low ^{3 5}
	159 per 1000	159 per 1000  (78 to 297)
Quality of life assessed with FOSQ: scale from 5 to 20 ‐ not measured	‐	‐	‐	‐	‐
AHI measured by number of events/hr Follow‐up: 4 weeks	The mean AHI (events/hr) was 4.2 events/hr	MD 0.3 events/hr higher  (0.95 lower to 1.55 higher)	‐	44  (1 RCT)	⊕⊕⊝⊝  Low ⁵
Blood pressure ‐ not measured	‐	‐	‐	‐	‐
Adverse events (machine tolerability outcomes)  assessed as number of participants experiencing a blocked nose Follow‐up: mean 4 weeks	Study population		OR 0.32  (0.16 to 0.63)	147  (2 RCTs)	⊕⊕⊝⊝  Low ⁶	This outcome was selected from different measures of nasal symptoms.
	648 per 1000	371 per 1000  (227 to 537)
*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; CI: confidence interval; CPAP: continuous positive airway pressure; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep Questionnaire; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial.
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.

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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.

Automatically adjusting continuous positive airway pressure (auto‐CPAP) versus fixed continuous positive airway pressure (fixed CPAP)

Primary outcomes

Machine usage

Auto‐CPAP probably increases average nightly usage by about 13 minutes per person compared with fixed CPAP at a median follow‐up of 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; Analysis 1.1, Figure 3). Average machine usage in the fixed CPAP arms was about five hours per person per night. Fixed‐effect and random‐effects meta‐analysis results were identical. Data from one large parallel group trial could not be used in the primary analysis because only medians and interquartile ranges were available (Pépin 2016, N = 322). We decided to incorporate this study as a sensitivity analysis because the sample size was bigger than any others in the analysis and the direction of effect was potentially discordant. Including this study 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).

1.1 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).

Forest plot of comparison: 1 Auto‐CPAP versus fixed CPAP, outcome: 1.1 Machine usage (hours/night).

1.2 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 2 Machine usage (hours/night) (Pepin imputed).

The number of people who use their machines for four hours or more per night may be slightly higher with auto‐CPAP, although the CIs include both substantially fewer and substantially more people with auto‐CPAP (odds ratio (OR) 1.16, 95% CI 0.75 to 1.81; 2 studies, 346 participants; low‐certainty evidence; Analysis 1.3).

1.3 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 3 Number of participants who used CPAP therapy > 4 hours per night.

Additional measures of usage indicate the increase in average effect could be driven by higher use on specific nights rather than incrementally greater use on all nights with auto‐CPAP (Analysis 1.4; Analysis 1.5; Analysis 1.6).

1.4 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 4 Machine usage (on nights when CPAP used 'effectively').

1.5 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 5 Machine usage (frequency of usage as % of days).

1.6 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 6 Machine usage (% of nights of > 4 hours of use) ‐ cross‐over studies.

Secondary outcomes

Symptom scores

Auto‐CPAP probably reduces the Epworth Sleepiness Scale (ESS) score by a small degree compared with fixed CPAP at three to 16 weeks (MD ‐0.44 units, 95% CI ‐0.72 to ‐0.16; 25 studies, 1285 participants; moderate‐certainty evidence; Analysis 1.7). Average ESS scores following fixed CPAP treatment ranged from 4.1 to 8.6. There was no statistical heterogeneity and changing statistical model had no impact on the pooled result.

1.7 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 7 Symptoms (Epworth Sleepiness Scale).

Withdrawals

The likelihood of withdrawal is probably similar between the two devices at six weeks (auto‐CPAP: 10% versus fixed CPAP: 11%), 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 participants; moderate‐certainty evidence; Analysis 1.8).

1.8 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 8 Withdrawals (parallel group trials/first arm cross‐over trials).

Quality of life scores

Functional Outcomes of Sleep Questionnaire (FOSQ)

Quality of life measured as FOSQ may be similar between auto‐CPAP and fixed CPAP (MD 0.12 units, 95% CI ‐0.21 to 0.46; 3 studies, 352 participants; low‐certainty evidence; Analysis 1.9). There was wide variation in the follow‐up for these studies (4 to 104 weeks).

1.9 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 9 Quality of life (Functional Outcomes of Sleep Questionnaire).

Sleep Apnoea Quality of Life Index (SAQLI)

Two trials assessing for changes in SAQLI found no significant difference in the effects of auto‐CPAP and fixed CPAP (MD ‐0.14 units, 95% CI ‐0.54 to 0.27; Analysis 1.10).

1.10 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 10 Quality of life (Sleep Apnoea Quality of Life Index).

Short‐Form 36 (SF‐36)

Eight studies provided data on quality of life measured with the SF‐36 (Analysis 1.11). The number of studies contributing data to each domain varied from two (role physical, bodily pain, general health and social functioning) to six (vitality). Effect sizes ranged from a reduction of 6 points with auto‐CPAP on physical health domain to a 6‐point increase with auto‐CPAP on general health domain. Hukins 2004 reported no significant differences between treatment groups.

1.11 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 11 Quality of life (SF‐36 questionnaire).

Sleep disruption

Apnoea Hypopnoea Index (AHI)

There is a slightly higher AHI with auto‐CPAP compared with fixed CPAP at six weeks (MD 0.48 events/hour, 95% CI 0.16 to 0.80; 26 studies, 1256 participants; high‐certainty evidence; Analysis 1.12). There was a high level of statistical heterogeneity that we could attribute to the inclusion of a single study (I² = 51%; Patruno 2007). Neither excluding Patruno 2007 nor applying a random‐effects model substantially altered the direction, precision or size of the effect.

1.12 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 12 Apnoea Hypopnoea Index (events/hr).

Arousals

There is insufficient evidence to determine the comparative effect of the devices on arousals (MD ‐0.66 events/hr, 95% CI ‐2.90 to 1.58; 4 studies, 136 participant; Analysis 1.13).

1.13 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 13 Arousals (events/hr).

Treatment pressure

There was a high degree of statistical variation in the size and direction of differences in treatment pressures across the studies (I² = 92%). Both fixed‐ and random‐effects models indicate lower 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 ‐2.12 to ‐0.85; 24 studies, 1171 participants; Analysis 1.14). Despite the different mechanisms used to deliver mask pressure between the devices, in some studies the delivered treatment pressure was equivalent between auto‐CPAP and fixed CPAP, whilst in others the mean treatment pressure in auto‐CPAP was between 3 cm H₂O and 5 cm H₂O lower. Differences in algorithms used by the different machines used to alter pressure (e.g. forced oscillation), variation in peak treatment pressure within study populations and the selection of participants on the basis of high treatment pressure required in others (e.g. Massie 2003; Noseda 2004), could contribute to the conflicting results.

1.14 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 14 Pressure of CPAP treatment (cmH₂O).

Blood pressure

Systolic blood pressure

Our analysis could not exclude a potentially small decrease or 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; moderate‐certainty evidence; Analysis 1.15). We were unable to extract data from Nolan 2007 and West 2006. Neither study reported significant differences between auto‐CPAP and fixed CPAP.

1.15 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 15 Systolic blood pressure.

Diastolic blood pressure

Diastolic blood pressure was higher at the end of the study period with auto‐CPAP than with fixed CPAP at 12 to 16 weeks (2.92 mmHg; 95% CI 1.06 to 4.77; 2 studies; 353 participants; low‐certainty‐evidence; Analysis 1.16). Nolan 2007 reported no significant difference between auto‐CPAP and fixed CPAP but did not provide numerical values.

1.16 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 16 Diastolic blood pressure.

Additional measures of blood pressure did not indicate any meaningful differences in blood pressure, namely 24‐hour mean, systolic and diastolic blood pressure: Analysis 1.17; Analysis 1.18 and Analysis 1.19); diurnal mean, systolic and diastolic blood pressure (Analysis 1.20; Analysis 1.21; Analysis 1.22), and nocturnal mean, systolic and diastolic blood pressure (Analysis 1.23; Analysis 1.24; Analysis 1.25).

1.17 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 17 24‐hour mean BP.

1.18 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 18 24‐hour systolic BP.

1.19 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 19 24‐hour diastolic BP.

1.20 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 20 Diurnal mean BP.

1.21 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 21 Diurnal systolic BP.

1.22 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 22 Diurnal diastolic BP.

1.23 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 23 Nocturnal mean BP.

1.24 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 24 Nocturnal systolic BP.

1.25 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 25 Nocturnal diastolic BP.

Adverse events

Data on tolerability outcomes were measured and reported inconsistently across the studies. We have presented a narrative summary of the data from individual studies for each main symptom associated with machine usage. Data from one study could be presented in Analysis 1.26. For the remainder, data were presented graphically or we could not adjust data adequately for the cross‐over design.

1.26 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 26 Tolerability outcomes.

Due to the risk of bias across the studies, variation in the methods used to measure this outcome and the use of unvalidated scales for some of the studies, we rated the certainty of evidence for tolerability outcomes to be very low (see Table 1). We have been unable to obtain data from one study of 181 people that measured CPAP side effects using the Edinburgh checklist but did not report these findings (Vennelle 2010). Follow‐up ranged from 4 to 36 weeks.

Nasal blockage

Four participants in Sériès 1997 suffered nasal blockage (2 from auto‐CPAP1 group, one from auto‐CPAP2, and one from fixed CPAP), which resolved with the use of a heated humidifier. Bloch 2018 presented data from the per protocol population, reporting similar rates of nasal blockage at 2 years (31% in both groups, N = 144). Nolan 2007 presented bar charts of those experiencing blocked or runny nose during both arms of treatment (just over 40% in those treated with auto‐CPAP and just over 30% in those with fixed CPAP based on visual inspection, N = 26).

Nussbaumer 2006 reported similar scores between treatment arms by participants who rated symptoms on a visual analogue scale (VAS) (N = 38).

Dry mouth

Bloch 2018 reported lower rates of dry mouth in the auto‐CPAP group than with fixed CPAP (46% versus 56%), whereas in Nolan 2007 the direction of effect was the reverse (just under 45% versus 35% with fixed CPAP, based on visual inspection).

Paticipant‐reported symptoms were slightly lower in the auto‐CPAP arm in Nussbaumer 2006.

Tolerance of treatment pressure

Bloch 2018 reported lower rates of excessive mask pressure with auto‐CPAP than with fixed CPAP (46% versus 51%), as did Nolan 2007 (18% versus 21%).

Massie 2003 reported a significant difference between auto‐CPAP and fixed CPAP in favour of the automatic pressure mode on feeling discomfort from pressure and experiencing less trouble getting to sleep (all values P < 0.006). Randerath 2001 reported no significant differences between the two groups who were treated with both auto and fixed CPAP (no numerical values presented). d'Ortho 2000 reported little difference on an unvalidated questionnaire measuring tolerance of treatment pressure between auto‐CPAP and fixed CPAP (N = 25). In Nussbaumer 2006 participant‐rated tolerance of treatment pressure was better in the auto‐CPAP arm than during fixed CPAP treatment.

Mask leak

Bloch 2018 reported a slightly higher proportion of participants reporting mask leak in the auto‐CPAP group (37% versus 34%); Nolan 2007 presented data that indicated slightly fewer participants experiencing leak with auto‐CPAP (just over 20% versus just under 25% based on visual inspection).

Teschler 2000 reported no significant difference in mask leak between fixed CPAP (13% mask on time with leak of 0.4 L/second) 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 person, leakage time or pressure leaked per second with auto‐CPAP compared with CPAP (Hukins 2004; West 2006; Galetke 2008; Damjanovic 2009). Nussbaumer 2006 found that mask leaks were perceived to be less problematic on auto‐CPAP than on fixed CPAP.

Participant preference

The results from the studies indicate wide variation in terms of preferences expressed by users of CPAP between the different machine types. In eight of the 14 studies reporting this outcome, on average people preferred auto‐CPAP over either fixed CPAP, or neither treatment. However, in six studies, people preferred fixed CPAP (Senn 2003; Hussain 2004; Jarvis 2006; To 2008; Vennelle 2010; Rohling 2011). In Senn 2003 the majority of participants (21/29) preferred neither treatment: but in Hussain 2004 (6/10) and To 2008 (30/41) the majority preferred treatment with fixed CPAP. In Jarvis 2006 (11/20), Vennelle 2010 (112/181) and Rohling 2011 (20/33), more participants expressed preference for fixed CPAP or no preference than preference for auto‐CPAP. We were unable to find a satisfactory explanation for this apparent discrepancy in terms of study design and technology of active interventions.

Bilevel positive airway pressure (Bi‐PAP) versus fixed CPAP

Primary outcomes

Machine usage

There is insufficient evidence to determine the effect of Bi‐PAP on average machine usage (0.14 hours/night, 95% CI ‐0.17 to 0.45; 4 studies; 268 participants; low‐certainty evidence; Analysis 2.1, Figure 4). Follow‐up ranged from 4 to 52 weeks.

2.1 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).

Forest plot of comparison: 2 Bi‐PAP versus fixed CPAP, outcome: 2.1 Machine usage (hours/night).

Secondary outcomes

Symptom scores

Epworth sleepiness scores (ESS) reduced from baseline with both devices in four studies with follow‐up from four to 12 weeks, but there is insufficient evidence available to determine the comparative effects of Bi‐PAP and fixed CPAP on symptoms (‐0.49 ESS units, 95% CI ‐1.46 to 0.48; 226 participants; low‐certainty evidence; Analysis 2.2).

2.2 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).

Withdrawals

There is insufficient evidence to determine whether withdrawal is 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 ranged from four to 52 weeks.

2.3 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross‐over trials).

Quality of life scores

Functional Outcomes of Sleep Questionnaire (FOSQ)

There is insufficient evidence from one small eight‐week trial to determine the effects of Bi‐PAP on FOSQ (low‐certainty evidence, Analysis 2.4).

Sleep Apnoea Quality of Life Index (SAQLI)

There is insufficient evidence to determine the effects of Bi‐PAP on SAQLI from one study (Analysis 2.5).

2.5 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 5 Quality of life (Sleep Apnoea Quality of Life Index).

Short‐Form 36 (SF‐36)

There is insufficient evidence to determine the effects of Bi‐PAP on SF‐36 sub domains of physical and mental health from one study (see Analysis 2.6).

2.6 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 6 Quality of life (SF‐36 questionnaire).

Sleep disruption

Apnoea Hypopnoea Index (AHI)

There is insufficient evidence from two studies at four to eight weeks duration to determine the effect of Bi‐PAP on AHI (1.36 events/hour, 95% CI ‐6.92 to 9.63; 2 studies; 179 participants; Analysis 2.7).

2.7 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 7 Apnoea Hypopnoea Index (events/hr).

Treatment pressure

Gulati 2015 provided a measurement of the two levels of pressure for inhalation and exhalation. Against a control mean of 11.45 cmH₂O the average pressure at inhalation was 13 cmH₂O and at exhalation was 4.1 cmH₂O.

Participant preference

Muir 1998 reported that both CPAP and bi‐PAP were preferred by 40% of participants, while 20% did not express a preference.

Adverse events

Follow‐up across the five studies providing information for these outcomes ranged from four to 52 weeks.

Reeves‐Hoché 1995 reported five withdrawals due to either mask discomfort (n = 2) or therapy intolerance (n = 3). All were from the CPAP group. No withdrawals due to mask discomfort or therapy intolerance occurred from the bi‐PAP group. Twenty participants complained of nasal dryness (no distribution between the 2 groups reported). Three participants complained of rhinorrhoea and 15 participants complained of nasal bridge pressure (no distribution reported between the 2 groups). Masa 2015 reported similar rates of dry mouth and mask intolerance in the treatment groups (Analysis 2.9).

2.9 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 9 Tolerability outcomes.

Gay 2003 reported that telephone contact did not identify any complications that necessitated further interventions. Muir 1998 did not report data in terms of specific adverse events; no difference 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 evidence to determine the effect (Bi‐PAP: 69 versus fixed CPAP: 60, P = 0.16).

CPAP with expiratory pressure relief (CPAPexp) versus fixed CPAP

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 follow‐up of two to 24 weeks (0.14 hours/night, 95% CI ‐0.07 to 0.35; 9 studies, 609 participants; low‐certainty evidence; Analysis 3.1, Figure 5).

3.1 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).

Forest plot of comparison: 3 CPAP with expiratory pressure relief versus fixed CPAP, outcome: 3.1 Machine usage (hours/night).

Secondary outcomes

Symptom scores

The effects of CPAPexp and fixed CPAP on symptom scores are probably similar in studies with a range of follow‐up of two to 24 weeks (0.17 ESS units, 95% CI ‐0.26 to 0.60; 6 studies, 515 participants; moderate‐certainty evidence; Analysis 3.2).

3.2 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).

Withdrawals

There is insufficient evidence to determine the effects of CPAPexp and fixed CPAP on withdrawal at 12 weeks (OR 0.86, 95% CI 0.48 to 1.55; 2 studies, 298 participants; low‐certainty evidence; Analysis 3.3).

3.3 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross‐over trials).

Quality of life

Functional Outcomes of Sleep Questionnaire (FOSQ)

There may be little difference in FOSQ between treatment modes based on evidence from one 12‐week study in 74 participants (‐0.40 FOSQ units, 95% CI ‐1.15 to 0.35; low‐certainty evidence; Analysis 3.4).

3.4 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep Questionnaire).

Short‐Form 36 (SF‐36)

Two studies reported SF‐36, but only one provided data suitable for analysis. There was insufficient evidence to determine the comparative effect of these treatment modes on the different domains of the SF‐36 (Analysis 3.5).

3.5 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 5 Quality of life (SF‐36 questionnaire).

Sleep disruption

Apnoea Hypopnoea Index (AHI)

There is little or no difference in AHI at the end of the study period ranging from four to 24 weeks (0.24 events/hr, 95% CI ‐0.49 to 0.96; 5 studies, 342 participants; high‐certainty evidence; Analysis 3.6).

3.6 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr).

Treatment pressure

There is probably little or no difference in treatment pressure between the two groups (‐0.05cmH₂O, 95% CI ‐0.63 to 0.52 cmH₂O; 2 studies, 241 participants; moderate‐certainty evidence; Analysis 3.7).

3.7 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 7 Pressure of CPAP treatment (cmH₂O).

Adverse events

No specific measures of nasal or oral symptoms were carried out in the trials which ranged in follow‐up from four to 24 weeks.

Four studies assessed treatment comfort scores. One parallel group trial reported data from questionnaires which indicated that CPAPexp was regarded as a more tolerable treatment than fixed CPAP by users, and led to greater satisfaction with treatment (Dolan 2008; Analysis 3.8; Analysis 3.9; Analysis 3.10). Gfüllner 2007 did not find a significant difference between the two treatments (measured as treatment comfort scores (CPAPexp: 6.9 versus fixed CPAP: 6.0). Nilius 2006 reported that after seven weeks of treatment, average 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 weeks revealed no statistically significant difference between the groups for any item. Pépin 2009 reported no statistically significant differences in assessments of side effects and comfort between the treatment modes.

3.8 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 8 Treatment satisfaction score.

3.9 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 9 Treatment comfort score.

3.10 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 10 Treatment interface score.

Mask leak

Bakker 2010 reported no significant difference between CPAPexp and fixed CPAP in 90th percentile leak (54.8 (standard deviation (SD) 19.5) and 59.8 (SD 20.8) L/min, P = 0.30), or in average leak (43.7 (SD 14.8) and 47.6 (SD 16.8) events/h, respectively; P = 0.31). Leidag 2008 reported that leakage in fixed CPAP mode was 27.5 (SD 11.5) L/min and in CPAPexp was 28.0 (SD 10) L/min.

Particpant preference

Leidag 2008 reported that the treatment modes were equally likely to be preferred by the study participants.

Heated humidification + fixed CPAP versus fixed CPAP alone

Primary outcomes

Machine usage

Humidification may increase use of fixed CPAP by 0.37 hours per 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 evidence; Analysis 4.1; Figure 6).

4.1 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 1 Machine usage (hours/night).

Forest plot of comparison: 4 Heated humidification + fixed pressure CPAP versus fixed pressure CPAP alone, outcome: 4.1 Machine usage (hours/night).

Secondary outcomes

Symptom scores

There may be little difference in ESS between those receiving humidification and those who did not based on four studies with a range of follow‐up of three to 12 weeks (MD ‐0.34, 95% CI ‐0.93 to 0.26; 184 participants; low‐certainty evidence; Analysis 4.2). Salgado 2006 reported no significant difference between treatments, but did not provide numerical values.

4.2 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 2 Symptoms (Epworth Sleepiness Scale).

Quality of life scores

Short‐Form 36 (SF‐36)

The effect of humidification on SF‐36 General Health Perception scores was uncertain (0.11, 95% CI ‐6.97 to 7.18; 2 studies; 124 participants, Analysis 4.5).

4.5 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 5 Quality of life (SF‐36 questionnaire).

Sleep disruption

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).

4.4 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 4 Apnoea Hypopnoea Index (events/hr).

Adverse events

Results for different unvalidated measures of nasal symptoms were reported by two studies as dichotomous data (Neill 2003; Ryan 2009), and by two studies as continuous data (Heiser 2010; Worsnop 2010). There was insufficient evidence to reliably determine the effect of additional humidification on symptoms of dry, runny, blocked or bleeding nose measured as either events (Analysis 4.6), or when rated as symptom scores (Analysis 4.7). The average duration was around four weeks.

4.6 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 6 Nasal symptoms (parallel group trials).

4.7 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 7 Nasal symptoms (parallel group trials).

Participant preference

Neill 2003 showed no significant difference in the number of participants expressing a preference for humidification over no humidification.

Multimodality devices versus fixed CPAP

Automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp) versus fixed CPAP

Kushida 2011 and Meurice 2009 compared auto C‐Flex with fixed CPAP. There was no evidence of a difference in compliance between the two devices (0.03 hours, 95% CI ‐0.66 to 0.67; 2 studies, 113 participants). Results for the remaining outcomes did not provide sufficient evidence to determine the effects on symptoms, quality of life or blood pressure (Analysis 5.2; Analysis 5.3; Analysis 5.4; Analysis 5.5; Analysis 5.6; Analysis 5.7; Analysis 5.8).

5.2 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).

5.3 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 3 Withdrawals (parallel group trials/first arm cross‐over trials).

5.4 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 4 Quality of life (Functional Outcomes of Sleep Questionnaire).

5.5 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 5 Apnoea Hypopnoea Index (events/hr).

5.6 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 6 Pressure of CPAP treatment (cmH₂O).

5.7 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 7 Systolic blood pressure.

5.8 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 8 Diastolic blood pressure.

Bi‐PAP with expiratory pressure relief (Bi‐PAPexp) versus fixed CPAP

Ballard 2007 compared Bi‐PAPexp (Bi‐Flex) to fixed CPAP in 104 participants who remained poorly compliant with fixed CPAP after standard interventions such as mask optimisation, humidification and sleep apnoea education; they reported increased machine use with Bi‐Flex, measured as an average of hours per night (3.7 hours 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 6.2). There was insufficient evidence to determine the effect on quality of life and no measurement of symptoms, withdrawals, AHI, blood pressure or adverse events.

6.1 — Comparison 6 Bi‐PAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).

6.2 — Comparison 6 Bi‐PAPexp versus fixed CPAP, Outcome 2 Number of participants who used CPAP therapy > 4 hours per night.

Automatically adjusting (auto bi‐PAP) versus fixed CPAP

Powell 2012 and Blau 2012 compared auto bi‐PAP with fixed CPAP in 83 participants with poor initial experience of CPAP. There was insufficient evidence to determine the effects on machine usage (MD 0.00 hours/night, 95% CI ‐0.70 to 0.70; Analysis 7.1), number of participants who used machines for more than four hours (Analysis 7.2), symptoms (Analysis 7.3), withdrawals (Analysis 7.4), quality of life (Analysis 7.5), and AHI (Analysis 7.6).

7.1 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 1 Machine usage (hours/night).

7.2 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 2 Number of participants who used CPAP therapy > trialist defined threshold.

7.3 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 3 Symptoms (Epworth Sleepiness Scale).

7.4 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 4 Withdrawals.

7.5 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 5 Quality of life (Functional Outcomes of Sleep Questionnaire).

7.6 — Comparison 7 Auto Bi‐PAP versus fixed CPAP, Outcome 6 Apnoea Hypopnoea Index (events/hr).

CPAP with expiratory pressure relief (CPAPexp) with wakefulness detection versus fixed CPAP

There was insufficient evidence from one study of CPAPexp designed to alter pressure as it detects wakefulness to determine the effects on machine usage, AHI, symptoms, quality of life and mask leak (Bogan 2017).

Discussion

Summary of main results

This updated systematic review includes 64 studies assessing the effect of pressure modification and humidification on clinical outcomes in adults with obstructive sleep apnoea (OSA). The addition of six studies to our main comparison has strengthened the conclusions from the previous version of this review regarding the comparative effects of automatically adjusting continuous positive airway pressure (auto‐CPAP) and CPAP with fixed pressure setting (fixed CPAP).

Auto‐CPAP probably increases machine usage by about 13 minutes per person per night when compared to fixed CPAP over three months (moderate‐certainty evidence). It probably reduces symptoms by a small amount (less than 0.5 points on the Epworth Sleepiness Scale (ESS)) over fixed CPAP (moderate‐certainty evidence). Fixed CPAP was slightly more effective at reducing the Apnoea Hypopnoea Index (AHI) (high‐certainty evidence) and it may lower diastolic blood pressure by 3 mmHg compared with auto‐CPAP (low‐certainty evidence). Variation in the approach to measuring adverse events from the devices meant that we could not determine whether the lower nightly average delivered treatment pressure of between 1 cmH₂O and 3 cmH₂O with auto‐CPAP had any associated impact on participant‐rated tolerability outcomes.

There is low‐certainty evidence that humidification increases average nightly machine usage, but more studies are needed to confirm this effect and to evaluate clinical outcomes, including symptoms and quality of life. The remaining studies reflect small, developing evidence bases for novel modes of pressure delivery, such as CPAP with expiratory pressure relief (CPAPexp) and automatically adjusting bilevel positive airway pressure (auto bi‐PAP).

Overall completeness and applicability of evidence

The populations recruited to the studies were predominantly male with a recent diagnosis of OSA and little previous exposure to CPAP. At baseline, the study populations had high body mass index (BMI) and AHI scores, and symptom scores indicated that they had excessive daytime sleepiness. Most of the studies to date have compared auto‐CPAP with fixed CPAP and measured machine usage, symptoms and AHI, with most studies completing measurement of outcomes at short term (i.e. 12 weeks or less). There is less information on quality of life, reflecting the relatively recent development and use of validated specific quality of life scales in OSA trials. The fragmentary nature of the evidence for tolerability outcomes, across all of the comparisons in the review, reflects different approaches to capturing information on these outcomes by the study investigators.

Auto‐CPAP versus fixed CPAP

The lack of associated clinically meaningful differences in 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 (Table 1). The end of treatment difference of 0.5 units is smaller than the minimal clinically important difference of between 2 and 3 (Patel 2018). There is evidence of a ceiling effect in symptoms once CPAP usage exceeds four hours per night (Weaver 2007). Many participants in both groups used machines for more than four hours per night, reducing the scope for any meaningful differences in symptoms (Appendix 3). It should also be acknowledged that average study duration was between 12 and 16 weeks; therefore one should be wary of using these short‐term results to predict long‐term outcomes.

Few studies have used OSA‐specific quality of life instruments. The mean differences in Functional Outcomes of Sleep Questionnaire (FOSQ) and Sleep Apnoea Quality of Life Index (SAQLI) scores between auto‐CPAP and fixed CPAP treatment arms did not exceed minimally important differences that have been reported for these questionnaires, i.e. 1 unit (Billings 2014). From generic Short‐Form 36 (SF‐36) questionnaire scores, auto‐CPAP participants reported a bodily pain score that was 4.2 units higher, a general health score that was 2.5 units higher and a role physical score that was 3.7 units lower than fixed CPAP participants. Whilst such differences have been reported to be clinically meaningful in other conditions (Swigris 2010; Ward 2014), it is unclear whether these results would translate into meaningful differences in OSA participants. The confidence intervals (CIs) around these effects are wide, and there are no studies specifying the minimally important difference in the SF‐36 questionnaire for adults with OSA.

Inconsistent approaches to measuring tolerability across the studies made it difficult to improve our understanding of harms from both device types. Although 11 studies reported on four main tolerability outcomes (nasal blockage, dry mouth, intolerance of treatment pressure and mask leak), combining data in a single analysis for any one outcome was not possible for our main comparison. Some studies measured tolerability outcomes dichotomously (Sériès 1997; Bloch 2018); others used a visual analogue scale (VAS) to enable participants to assess the impact of various adverse events (d'Ortho 2000; Massie 2003; Nussbaumer 2006). A standardised approach to measuring CPAP tolerability has yet to become universally adopted (Boström 2010b). Building on existing efforts to arrive at an agreed approach to the definition and measurement of tolerability outcomes in CPAP research would help to improve our understanding of the relationship between tolerability, continued machine usage and symptomatic changes.

At the end of the study period, participants on fixed CPAP had a diastolic blood pressure that was almost 3 mmHg lower than participants on auto‐CPAP. It is certainly biologically plausible that fixed CPAP is more effective than auto‐CPAP in lowering diastolic blood pressure. Diastolic hypertension is thought to arise from peripheral vasoconstriction, which itself is a consequence of sympathetic activation (Pépin 2014). Auto‐CPAP has been associated with more sympathetic activation than fixed CPAP (Patruno 2014), which may lead to relative diastolic hypertension in people who are using auto‐CPAP. Furthermore, we observed a slightly higher AHI in auto‐CPAP participants, which could be associated with increased sympathetic activation.

Given the high rates of compliance, the reduction in diastolic blood pressure achieved by fixed CPAP in relation to auto‐CPAP may have implications for cardiovascular outcomes. Cook 1995 reported that a 2 mmHg drop in diastolic blood pressure could reduce risk of coronary heart disease by 6% and risk of stroke and transient ischaemic attack by 15%. Similarly, Law 2009 reported that a drop of 5 mmHg in diastolic blood pressure would reduce risk of coronary disease by 25% and risk of stroke by 36%.

On balance, we remain cautious about the effect on diastolic blood pressure. Diastolic blood pressure was one of 11 parameters of blood pressure that were analysed in this review; thus we cannot exclude multiplicity as a cause of this finding. Other parameters of blood pressure from larger sample sizes did not show similar effects (clinic systolic or 24‐hour, diurnal or nocturnal systolic, diastolic or mean blood pressure). Baguet 2013 argue that 24‐hour ambulatory blood pressure monitoring rather than office‐measured blood pressure is necessary to detect masked hypertension (i.e. normal office BP but elevated ambulatory measurements) which is present in 30% of adults with OSA and is a known risk factor for cardiovascular disease (Bobrie 2008; Angeli 2010). Our confidence in this effect was low due to very serious inconsistency; Patruno 2007 reported that fixed CPAP participants had a diastolic blood pressure that was almost 7 mmHg lower than auto‐CPAP participants; Pépin 2016 reported this difference to be less than 2 mmHg. Furthermore Pépin 2016 reported that the mean change in diastolic blood pressure from baseline did not differ between fixed CPAP and auto‐CPAP. Finally, in the nine ambulatory measurements of blood pressure made by Pépin 2016 and Bloch 2018, there were no differences between fixed CPAP and auto‐CPAP in any blood pressure parameter, either at the end of the study period or in the mean change from baseline.

There is weak consensus among investigators as to the optimal measurement of blood pressure in adults with OSA. Future research should identify which parameter of blood pressure best correlates with cardiovascular morbidity and mortality in adults with OSA. The effect on diastolic blood pressure requires further clarification given the risks associated with hypertension in OSA and recent evidence suggesting that auto‐CPAP and fixed CPAP produce different biological effects (Marrone 2018).

Effects in previous users of CPAP

People who have previously used CPAP prior to study entry are under‐represented in studies included in our review. Although we have not been able to carry out formal subgroup analysis, the results of the studies that have recruited from this population do not provide evidence of substantially different results in terms of both usage or functional outcomes. Rostig 2003 showed that auto‐CPAP improved compliance by about 30 minutes in a cross‐over trial of 30 participants who were on long‐term CPAP but whose hours of use were less than four hours per night. Ballard 2007 showed that Bi‐Flex improves machine usage by 36 minutes compared to fixed CPAP in participants with CPAP compliance of less than four hours per night, despite undergoing a CPAP optimisation intervention; however, there were no differences in FOSQ scores between the two groups. Gulati 2015 found that both Bi‐PAP or an alternative fixed CPAP device improved compliance by over two hours in participants with symptoms of pressure intolerance and fixed CPAP use of less than four hours per night; however, there were no significant differences between Bi‐PAP and alternative CPAP in terms of hours of use, ESS, Oxford Sleep Resistance (OSLER) sleep latency or SAQLI score. Powell 2012 showed that auto bi‐PAP did not improve CPAP compliance, ESS or FOSQ score in participants with a suboptimal CPAP titration.

Certainty of the evidence

The certainty of evidence varied across the different outcomes for the four comparisons we assessed. Our downgrading decisions were based on concerns about risk of bias, imprecision or inconsistency, although their impact varied across the different outcomes.

In the comparison of auto‐CPAP and fixed CPAP we downgraded the certainty of evidence for average machine usage to moderate due to risk of bias, and machine usage for four hours or more per night to low for risk of bias and imprecision (Table 1). For the remaining comparisons, we downgraded average machine usage to low for risk of bias and imprecision. We rated effects on symptoms as moderate certainty for auto‐CPAP and CPAPexp due to risk of bias (Table 1; Table 3), and as low for Bi‐PAP and humidification due to risk of bias and imprecision (Table 2; Table 4).

Across all the comparisons, the certainty of evidence for quality of life outcomes is low and this reflects the relatively recent use of validated scales in sleep apnoea trials. The very low‐certainty evidence for tolerability outcomes for all the comparisons is due to variation in how this outcome has been measured across the studies. We rated the certainty of evidence for AHI as high for the comparisons of auto‐CPAP and CPAPexp with fixed CPAP (Table 1; Table 3). We would expect the impact of long‐term attrition to be smaller on these outcomes, as the results are consistent with immediate changes to sleep disturbance which arise from using positive airway pressure, irrespective of the device. In the comparison of auto‐CPAP and fixed CPAP, we regard attrition as a less important source of uncertainty on the size of effect on diastolic blood pressure than variation in effect size between the studies (Table 1).

Potential biases in the review process

Before updating this review we made a number of changes to the methods that we had previously implemented (see Differences between protocol and review). We decided to combine data from parallel and cross‐over studies for the 2019 update of the review. We acknowledge that this decision could introduce methodological variation by combining data from short‐term within‐participant studies with parallel group studies that have a longer‐term follow‐up where between‐participant differences could attenuate over time. We used adjusted data, where possible, to account for the within‐person design of cross‐over studies. However, for a number of analyses of 'Summary of findings' table outcomes, we used unadjusted data (Analysis 1.1; Analysis 1.7; Analysis 1.12; Analysis 1.14; Analysis 3.1; Analysis 3.2; Analysis 3.6; Analysis 4.1; Analysis 4.4). It is possible that individual study weights are artificially low without a reasonable estimate of the within‐person correlation. The impact of this approach on the summary effect estimates is small, since only 10% to 15% of total sample size are affected across the analyses, and the direction and size of effect of the studies affected are aligned with the summary effect sizes. The consistent direction and size of effect for usage, symptom and AHI outcomes provides some support to our approach in combining the study designs and adjustment of the cross‐over studies.

Our decision to use a threshold of four hours as a measure of adequate machine usage could be contested. We chose this threshold as research indicates that resolution of daytime sleepiness requires a minimum of four hours of CPAP use per night (Weaver 2007). The optimal 'dose' of CPAP selected will depend on whether the intention of treatment is to modify blood pressure, subjective or objective sleepiness, functional status, as well as what individuals require (Masa 2014; Bakker 2019). Whilst it is likely that optimal dosing does indeed vary between individuals and by therapeutic aim, we have retained the view that a consistently applied threshold across a population that reflects symptomatic change reflects an important goal of treatment for adults with OSA. In the absence of more refined ways of identifying changes in individuals, we think that continuous and dichotomous measurements of machine usage provide complementary insights to inform treatment decisions.

Agreements and disagreements with other studies or reviews

Two other meta‐analyses have compared auto and fixed CPAP (Ip 2012; Xu 2012), and a third network meta‐analysis compared auto‐CPAP, fixed CPAP and oral appliances (Liu 2017). Ip 2012 and Xu 2012 report very similar effect sizes to our own, with auto‐CPAP resulting in an additional 11 minutes and 14 minutes of nightly usage, respectively. Ip 2012 also found a small decrease in ESS with auto‐CPAP and Xu 2012 reported statistically significant decreases in treatment pressure with auto‐CPAP.

Ip 2012 estimated that fixed CPAP lowered diastolic blood pressure by 8 mmHg (95% CI 4 to 11 mmHg, P < 0.001) more than auto‐CPAP. This 8 mmHg difference is markedly greater than that observed in our study (3 mmHg); the more modest effect in our study is likely due to the inclusion of Pépin 2016 which showed a more attenuated effect of fixed CPAP on diastolic blood pressure. Similar to our analysis, Ip 2012 had insufficient confidence in this effect. Liu 2017 reported no difference in the effects of fixed CPAP and auto‐CPAP on 24‐hour diastolic, 24‐hour systolic, diurnal systolic, diurnal diastolic, nocturnal systolic or nocturnal diastolic blood pressure in direct pair‐wise comparisons; office diastolic blood pressure was not included in this analysis. Interestingly, Liu 2017 ranked fixed CPAP above auto‐CPAP in its likelihood to reduce diurnal systolic (67.44% versus 45.21%) diurnal diastolic (58.75% versus 29.37%), nocturnal systolic (63.1% versus 45.93%) and nocturnal diastolic blood pressure (62.76% versus 32.57%), although no assessment of the certainty of this evidence was provided.

One meta‐analysis has been published comparing flexible titration modalities of CPAP with fixed CPAP (Bakker 2011). Despite some methodological differences relating to the eligibility of short‐term studies and separation of parallel and cross‐over studies, the effect sizes for machine usage and AHI are similar to our own.

Authors' conclusions

Implications for practice.

In adults with moderate to severe sleep apnoea who are starting positive airway pressure therapy, average machine usage is probably increased by about 13 minutes per night with 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 either device leads to more people using machines for four hours or more (low certainty). The reduction in daytime sleepiness associated with the average increased use of auto‐CPAP is small (moderate‐certainty evidence), and fixed CPAP is slightly more effective at reducing the Apnoea Hypopnoea Index (AHI) (high‐certainty evidence). Most of the studies to date have followed participants for shorter than 12 weeks. It is unclear whether modifying pressure in participants with mild and less pronounced sleep apnoea symptoms is beneficial. About 25% of people recruited to the studies are female. Generally, research to date has not addressed what interventions are effective in people who find CPAP difficult to tolerate.

Use of specific quality of life instruments in the studies to date has been limited, although where they have been used the effect sizes have not exceeded clinically important differences. Evidence for blood pressure outcomes is insufficient to determine the anti‐hypertensive effects between the different machine types. Tolerabillty outcomes were measured too inconsistently to further our understanding of how varying treatment pressure with auto‐CPAP changes the experience of applying positive airway pressure.

The evidence base for the remaining interventions included in the review is smaller, with a similar focus on machine usage and symptoms over quality of life. The effect on machine usage with expiratory pressure CPAP (CPAPexp) is uncertain and there is little or no difference in symptoms when compared with fixed CPAP. Although there is some evidence of higher machine usage following the addition of humidification, the certainty of evidence is low, and the effects on symptoms and tolerability are uncertain. Effects of humidification may also be affected by local ambient humidity.

Implications for research.

Study investigators and research funders initiating further research in this area should address the following issues related to the design, analysis and reporting of studies.

To date, only a small proportion of eligible trials have recruited people who have been unable to persist with CPAP. Further trials in this population are needed to inform decisions between alternative management strategies where acceptability of CPAP is lower than in the populations recruited to studies in this review.
Assessment of the effects of different pressure machines in studies that recruit a greater proportion of women and participants with lower AHIs than those in the existing studies would broaden the applicability of the evidence base.
Adoption of a standardised approach to defining machine tolerability is needed. Variation in the definition and measurement of machine tolerability has made it challenging to evaluate the harms from using different pressure modes, and to determine their relationship with machine usage. Agreement on consistent approaches to measuring mask leak, pressure tolerance, and oral and nasal symptoms would help decision‐makers to balance benefits with harms from different treatment options available. Consensus on which blood pressure parameters to measure is needed in order to better understand the relationship between blood pressure and long‐term cardiovascular outcomes.
We are aware of one large completed study (N = 800) comparing auto‐CPAP and fixed CPAP, which we expect to incorporate in future versions of this review when its results are available (NCT02749812). Two smaller ongoing studies are addressing similar outcomes to those already addressed (ACTRN12618000379213p; NCT03428516). Future studies should include longer‐term follow‐up and measure quality of life.
We have identified one ongoing study of CPAPexp (NCT01753999), and large multicentre studies in bilevel positive airway pressure (bi‐PAP), CPAPexp, humidification and automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp) are warranted.
Studies should better report design features (e.g. blinding and allocation concealment) and be more explicit about handling data from participants who do not continue to use machines during the studies.
Given the range of treatment options that continue to emerge, head to head comparisons between different ways of modifying pressure would help to inform choice of treatment where alternatives to fixed CPAP are being considered. Such studies could also serve as a basis for a network meta‐analysis of pressure modification strategies, including a cost‐effectiveness assessment to inform local decision making.

What's new

Date	Event	Description
15 October 2018	New search has been performed	Search run and 21 studies included. 2 studies previously included 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 have changed	Additional evidence has increased certainty in previous findings. New data on blood pressure have been included. We updated the methods to reflect current Cochrane standards e.g. adding a 'Summary of findings' table and PRISMA diagram.

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History

Protocol first published: Issue 3, 2001  Review first published: Issue 4, 2004

Date	Event	Description
10 September 2008	New citation required and conclusions have changed	Review split; 28 trials added to review; new data available for primary 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 humidification 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 have changed	Substantive amendment

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Acknowledgements

The Background and Methods sections of this review are based on a standard template used by Cochrane Airways.

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Airways Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service (NHS), or the Department of Health.

We are grateful to previous author Muzlifah Hanifa who initiated the protocol and was involved with study assessment, data collection and entry, and drafting of the discussion and conclusions. We are very grateful to the members of the Cochrane Airways Group editorial base who gave support with searching for studies, and to Prof John Wright for constructive comments on the protocol and the review on previous versions of the review. We are grateful for assistance given to us by study investigators who provided additional information about their studies: Konrad Bloch (Bloch 2018), Atul Gulati (Gulati 2015), Jessie Bakker (Bakker 2010), Naricha Chirakalwasan (Soudorn 2016), Evan Chang (Chang 2015), Timon Fabius (Rohling 2011), Domagoj Damjanovic (Damjanovic 2009), Maik Schroder (Nilius 2006), Silke Ryan (Ryan 2009), Nathalie Arnol and Jean‐Louis Pepin (Pépin 2009; Pépin 2016), Christopher Worsnop (Worsnop 2010), Alexander Blau (Blau 2012), Leon Rosenthal (Dolan 2008), Marie‐Pia d'Ortho (d'Ortho 2000), Nat Marshall (Marshall 2008), Adrian Kendrick (Kendrick 2002), Clifford Massie (Massie 1999; Massie 2003), Nancy Gordon (Massie 1999; Massie 2003), Sophie West and John Stradling (West 2006), Geraldine Lawless (Nolan 2007), Doug McEvoy (Morton 2001), Winfried Randerath (Randerath 2001), Frederic Sériès (Meurice 1996; Sériès 1997; Sériès 2001; Meurice 1998), Peter Cistulli (Jarvis 2006), David Hui (To 2008) and Jean‐Claude Meurice (NCT02749812).

The authors and CRG Editorial Team are grateful to the following peer and consumer reviewers for their time and comments.

Hayley Barnes, The Alfred Hospital, Melbourne.
Nathaniel Marshall, University of Sydney and the Woolcock Institute for Medical Research, Sydney.
PR Srijithesh, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
Jose‐Ramon Rueda, University of the Basque Country, Lejona, Spain.
Ndi Euphrasia Ebai‐Atuh, Consumer Reviewer, Cameroon.

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

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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

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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.

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:

(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	Completed	% Screened	% Entered	Mean hours used (control 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 reported	N/A	N/A	Not reported
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 (assumed)	10	N/A	100	3.7
Jarvis 2006	Not reported	Not reported	20	N/A	N/A	6.8
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 reported	N/A	N/A	Not reported
Marrone 2004	Not reported	22 (assumed)	22	N/A	100	4.4
Marshall 2008	Not reported	Not reported	19	N/A	NA	3
Masa 2015	351	221 (numbers reported here reflect participants screened for three treatment arms)	200	57%	90%	5.3
Massie 2003	Not reported	46	44	N/A	95.6	4.5
Meurice 1996	Not reported	16	16	N/A	100	5.7
Meurice 2007	Not reported	83	65	N/A	78	6.5
Meurice 2009	Not reported	20	20	N/A	100	5.3
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 (average 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
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 (assumed)	N/A	100 (assumed)	3.8
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 (assumed)	N/A	100 (assumed)	4.2
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 (assumed)	20	NA	100 (assumed)	5.8
West 2006	633	98	86	16	88	5.6
Worsnop 2010	Not reported	54	54 (assumed)	N/A	100 (assumed)	4.5
Abbreviations: N/A: not applicable

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Data and analyses

Comparison 1. Auto‐CPAP versus fixed CPAP.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Machine usage (hours/night)	31	1452	Mean Difference (Fixed, 95% CI)	0.21 [0.11, 0.31]
2 Machine usage (hours/night) (Pepin imputed)	32	1774	Mean Difference (Fixed, 95% CI)	0.19 [0.10, 0.29]
3 Number of participants who used CPAP therapy > 4 hours per night	2	346	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.75, 1.81]
4 Machine usage (on nights when CPAP used 'effectively')	3		Mean Difference (Fixed, 95% CI)	0.42 [0.05, 0.78]
5 Machine usage (frequency of usage as % of days)	9		Mean Difference (Fixed, 95% CI)	1.60 [‐0.83, 4.03]
6 Machine usage (% of nights of > 4 hours of use) ‐ cross‐over studies	2		Mean Difference (Fixed, 95% CI)	6.25 [‐0.05, 12.54]
7 Symptoms (Epworth Sleepiness Scale)	25	1285	Mean Difference (Fixed, 95% CI)	‐0.44 [‐0.72, ‐0.16]
8 Withdrawals (parallel group trials/first arm cross‐over trials)	13	1275	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.64, 1.27]
9 Quality of life (Functional Outcomes of Sleep Questionnaire)	3	352	Mean Difference (Fixed, 95% CI)	0.12 [‐0.21, 0.46]
10 Quality of life (Sleep Apnoea Quality of Life Index)	2	97	Mean Difference (Fixed, 95% CI)	‐0.14 [‐0.54, 0.27]
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]
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% CI)	1.87 [‐1.08, 4.82]
16 Diastolic blood pressure	2	353	Mean Difference (IV, Fixed, 95% CI)	2.92 [1.06, 4.77]
17 24‐hour mean BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.59 [‐1.05, 2.22]
18 24‐hour systolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐2.21, 1.91]
19 24‐hour diastolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.90 [‐0.65, 2.44]
20 Diurnal mean BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.63 [‐1.05, 2.32]
21 Diurnal systolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	‐0.35 [‐2.44, 1.74]
22 Diurnal diastolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.91 [‐0.74, 2.55]
23 Nocturnal mean BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.43 [‐1.29, 2.15]
24 Nocturnal systolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.88 [‐1.81, 3.57]
25 Nocturnal diastolic BP	2	530	Mean Difference (IV, Fixed, 95% CI)	0.80 [‐0.81, 2.40]
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 auto‐CPAP)	14		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

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1.27 — Comparison 1 Auto‐CPAP versus fixed CPAP, Outcome 27 Patient preference (auto‐CPAP/not auto‐CPAP).

Comparison 2. Bi‐PAP versus fixed CPAP.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Machine usage (hours/night)	4	268	Mean Difference (Fixed, 95% CI)	0.14 [‐0.17, 0.45]
2 Symptoms (Epworth Sleepiness Scale)	4	226	Mean Difference (Fixed, 95% CI)	‐0.49 [‐1.46, 0.48]
3 Withdrawals (parallel group trials/first arm cross‐over trials)	3	261	Odds Ratio (M‐H, Fixed, 95% CI)	0.55 [0.26, 1.17]
4 Quality of life (Functional Outcomes of Sleep Questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5 Quality of life (Sleep Apnoea Quality of Life Index)	1		Mean Difference (Fixed, 95% CI)	Totals not selected
6 Quality of life (SF‐36 questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
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 (events/hr)	2	179	Mean Difference (Fixed, 95% CI)	1.36 [‐6.92, 9.63]
8 Patient preference ‐ BiPAP/no preference or CPAP	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
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

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2.8 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 8 Patient preference ‐ BiPAP/no preference or CPAP.

2.10 — Comparison 2 Bi‐PAP versus fixed CPAP, Outcome 10 Treatment comfort score.

Comparison 3. CPAPexp versus fixed CPAP.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Machine usage (hours/night)	9	609	Mean Difference (Fixed, 95% CI)	0.14 [‐0.07, 0.35]
2 Symptoms (Epworth Sleepiness Scale)	6	515	Mean Difference (Fixed, 95% CI)	0.17 [‐0.26, 0.60]
3 Withdrawals (parallel group trials/first arm cross‐over trials)	2	298	Odds Ratio (M‐H, Fixed, 95% CI)	0.86 [0.48, 1.55]
4 Quality of life (Functional Outcomes of Sleep Questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5 Quality of life (SF‐36 questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.1 Physical functioning	1	76	Mean Difference (IV, Fixed, 95% CI)	6.20 [‐3.05, 15.45]
5.2 Role physical score	1	76	Mean Difference (IV, Fixed, 95% CI)	‐9.5 [‐25.38, 6.38]
5.3 Bodily pain score	1	76	Mean Difference (IV, Fixed, 95% CI)	7.20 [‐3.69, 18.09]
5.4 General health score	1	76	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐8.05, 10.05]
5.5 Vitality	1	76	Mean Difference (IV, Fixed, 95% CI)	‐2.5 [‐11.38, 6.38]
5.6 Social functioning score	1	76	Mean Difference (IV, Fixed, 95% CI)	‐8.30 [‐17.87, 1.27]
5.7 Role emotional score	1	76	Mean Difference (IV, Fixed, 95% CI)	‐7.30 [‐21.83, 7.23]
5.8 Mental health score	1	76	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐4.86, 8.86]
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% CI)	‐0.05 [‐0.63, 0.52]
8 Treatment satisfaction score	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9 Treatment comfort score	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10 Treatment interface score	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
11 Preference	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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3.11 — Comparison 3 CPAPexp versus fixed CPAP, Outcome 11 Preference.

Comparison 4. Heated humidification + fixed CPAP versus fixed CPAP alone.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
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]
3 Withdrawals (parallel group trials/first arm cross‐over trials)	3	209	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.45, 2.24]
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, 95% CI)	Subtotals only
7.1 Dry nose	2	103	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐0.78, 0.01]
7.2 Runny nose	2	103	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐0.69, 0.09]
7.3 Blocked nose	2	103	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐0.78, 0.01]
7.4 Bleeding nose	2	103	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐0.99, 0.10]
8 Preference	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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4.3 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 3 Withdrawals (parallel group trials/first arm cross‐over trials).

4.8 — Comparison 4 Heated humidification + fixed CPAP versus fixed CPAP alone, Outcome 8 Preference.

Comparison 5. Auto‐CPAPexp versus fixed CPAP.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Machine usage (hours/night)	2	113	Mean Difference (Fixed, 95% CI)	0.03 [‐0.60, 0.67]
2 Symptoms (Epworth Sleepiness Scale)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3 Withdrawals (parallel group trials/first arm cross‐over trials)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4 Quality of life (Functional Outcomes of Sleep Questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5 Apnoea Hypopnoea Index (events/hr)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
6 Pressure of CPAP treatment (cmH₂O)	2	113	Mean Difference (Fixed, 95% CI)	‐0.92 [‐1.77, ‐0.07]
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

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5.1 — Comparison 5 Auto‐CPAPexp versus fixed CPAP, Outcome 1 Machine usage (hours/night).

Comparison 6. Bi‐PAPexp versus fixed CPAP.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Machine usage (hours/night)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
2 Number of participants who used CPAP therapy > 4 hours per night	1	Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3 Quality of life (Functional Outcomes of Sleep Questionnaire)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected

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6.3 — Comparison 6 Bi‐PAPexp versus fixed CPAP, Outcome 3 Quality of life (Functional Outcomes of Sleep Questionnaire).

Comparison 7. Auto Bi‐PAP versus fixed CPAP.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Machine usage (hours/night)	2		Mean Difference (Fixed, 95% CI)	‐0.00 [‐0.70, 0.70]
2 Number of participants who used CPAP therapy > trialist defined threshold	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
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]
5 Quality of life (Functional Outcomes of Sleep Questionnaire)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
6 Apnoea Hypopnoea Index (events/hr)	1		Mean Difference (Fixed, 95% CI)	Totals not selected

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Comparison 8. CPAPexp with wakefulness detection versus fixed CPAP.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Machine usage (hours/night)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
2 Symptoms (Epworth Sleepiness Scale)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
3 Quality of life (Functional Outcomes of Sleep Questionnaire)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
4 Apnoea Hypopnoea Index (events/hr)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
5 Mask leak	1	Mean Difference (Fixed, 95% CI)	Totals not selected

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8.1 — Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 1 Machine usage (hours/night).

8.2 — Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 2 Symptoms (Epworth Sleepiness Scale).

8.3 — Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 3 Quality of life (Functional Outcomes of Sleep Questionnaire).

8.4 — Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 4 Apnoea Hypopnoea Index (events/hr).

8.5 — Comparison 8 CPAPexp with wakefulness detection versus fixed CPAP, Outcome 5 Mask leak.

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	Machine usage (average hours used and average days used) Quality of life (FOSQ and SF‐36) AHI Symptoms (ESS) Withdrawals Treatment pressure Tolerability (mask leak)
Funding & conflicts of interest statements	'This study was funded by Philips‐Respironics. All authors received research support from Philips‐Respironics. Philips‐Respironics manufactures and markets CPAP and C‐Flex devices.'
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization to treatment was performed prior to manual titration using a (1, 2) urn randomization procedure"
Allocation concealment (selection bias)	Low risk	Quote: "Randomization to treatment was performed prior to manual titration using a (1, 2) urn randomization procedure"
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The study was a double‐blinded, parallel‐arm RCT of C‐Flex versus CPAP" Quote: "Patients were not able to access the C‐Flex menu option, and all references to "C‐Flex" on the device were covered"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Quote: "The study was a double‐blinded, parallel‐arm RCT of C‐Flex versus CPAP" Quote: "Patients were not able to access the C‐Flex menu option, and all references to "C‐Flex" on the device were covered"
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Quote: "The data analyst remained blinded by random 3‐digit codes being assigned to all patients"
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "Two patients were withdrawn".........2 patients dropped out of the CPAP group............they were replaced with additional recruitment, and therefore analysis was conducted on a per‐protocol basis"
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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	Machine usage (average hours used and using therapy > 4 hrs) Quality of life (FOSQ)
Funding & conflicts of interest statements	Quote: "This study was supported by a grant from Respironics, Inc. Respironics reimbursed National Jewish Medical and Research Center for part of Dr. Ballard’s time. Dr. Gay has received research support from ResMed. Dr. Strollo has indicated no financial conflicts of interest."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were then provided a modified positive airway pressure device (BiPAP Pro, Respironics Inc.) randomly set to either CPAP or BiFlex mode at appropriate pressure(s)"
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were then provided a modified positive airway pressure device (BiPAP Pro, Respironics Inc.) randomly set to either CPAP or BiFlex mode at appropriate pressure(s)"
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Both patients and the investigators were blinded as to the specific mode assigned to each patient."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Quote: "Both patients and the investigators were blinded as to the specific mode assigned to each patient."
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Study reported to have been analysed on ITT principles. Unlikley to bias machine usage data but quality of life collected from completers. There was differential dropout and this may have influenced the results.
Selective reporting (reporting bias)	Unclear risk	Insufficient information available
Other bias	Low risk	No concerns identified

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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 Exclusion criteria: previous CPAP therapy; shift work; unstable depression/psychosis; non‐adherence with medication; COPD; uncontrolled hypertension or restless legs syndrome; narcolepsy; supplemental oxygen use; congestive heart failure; nightly narcotic use; hypoventilation; neuromuscular weakness; 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 Study duration: 6 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Quality of life (FOSQ) Treatment pressure Withdrawals
Funding & conflicts of interest statements	Quote: "This study was supported by a research grant from the Res Med Foundation and an unrestricted 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 routine 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 support from research funding. This work was also supported by resources provided by the North Florida/South Georgia Veterans Health System, Gainesville, FL. The contents of this paper do not represent 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient details available to determine process
Allocation concealment (selection bias)	Low risk	Quote: "The method of randomization was by opening sequential envelopes prepared by the research service."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study had open‐label design which likely affects usage, symptoms, quality of life attrition outcomes.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by open‐label design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Impact of study design on outcome assessment related to nature of outcome. Usage, AHI and treatment pressure measured from technical readings. Symptoms, quality of life more likely affected by open‐label design.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Treatment pressure and AHI unlikely to be affected by open‐label design.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Balanced but potentially meaningful dropout which was slightly higher in fixed CPAP group (19/78 versus 12/78). Participants not using machines at clinic visit 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 (reporting bias)	Low risk	All prespecified outcomes presented according to details provided on trials registry record.
Other bias	Low risk	No concerns identified

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Blau 2012.

Methods	Randomised, double‐blind, parallel group trial
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 Study duration: 12 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Withdrawals Treatment pressure
Funding & conflicts of interest statements	Quote: "This study was supported by an unrestricted grant from Philips Respironics, Inc. 1001 Murry 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 article."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "We generated a list of N = 32 uniformly distributed pseudo‐random numbers of either 0 (CPAP) or 1 (Auto bi‐level) by using the Mersenne Twister algorithm"
Allocation concealment (selection bias)	Low risk	Quote: "The allocation of the patient was told directly via telephone in case of randomisation from an not otherwise involved team member, situated in another campus of our university clinic."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Devices were set by the study coordinators who deactivated the LCD display so that the patient and investigators did not become aware of device allocation" Quote: "There were no concrete information about characteristics of these different PAP types in the informed consent"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Quote: "Devices were set by the study coordinators who deactivated the LCD display so that the patient and investigators did not become aware of device allocation"
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The investigator making and analysing the PSG recordings on therapy and other outcome measures did not have access to information from the therapy device within their PSG montage"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	3 withdrawals after allocation (1 from CPAP group and 2 from ABRP‐PAP group); these patients were not included in analysis.
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Bloch 2018.

Methods	Randomised, double‐blind, parallel group trial
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 obstruction, 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
Outcomes	Machine usage (average hours used) Symptoms (ESS) AHI Quality of life (SF‐36, FOSQ) Treatment pressure Blood pressure Adverse events
Funding & conflicts of interest statements	Quote: "The study was supported by the Swiss National Science Foundation, the lung leagues of Zurich, 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 reports 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 competing interests."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation of participants was performed according to a 1:1 balanced block design by the study centre.......envelopes containing codes for the treatment mode and CPAP brand 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."
Allocation concealment (selection bias)	Low risk	Quote: "...envelopes containing codes for the treatment mode and CPAP brand 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 and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "True blinding of participants and clinical care‐givers was not feasible since all participants had an initial phase of autoCPAP therapy." This is likely to impact on usage data, quality of life and symptom scores.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "True blinding of participants and clinical care‐givers was not feasible since all participants had an initial phase of autoCPAP therapy." This is likely to impact on usage data, quality of life and symptom scores
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	15 out of 95 randomised to fixed CPAP group withdrew from treatment by 24 months. 21 out of 113 randomised to auto‐CPAP group withdrew from treatment by 24 months. Data were presented for ITT analysis and per protocol. Multiple imputation method used to address attrition. In view of large attrition 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 effects.
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 medications; surgery of the mouth, nose, sinuses, or airways in previous 12 months; patients who are required 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	Machine use (average hours used last 2 weeks of treatment) Symptoms (ESS) Quality of life (Short form FOSQ) AHI Mask leak
Funding & conflicts of interest statements	Quote: "The authors declare that there are no conflicts of interest regarding the publication of this paper. 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 Healthcare. 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 evaluated 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Random permuted blocks were used to randomise patients into the two treatment sequence groups."
Allocation concealment (selection bias)	Low risk	Quote: "The randomization records were kept in a patient master log. The study coordinator set the device to the appropriate treatment arm according to the patient master log during the device setup visit." The process described is consistent with an approach that conceals the assignment from both the study personnel and the participants and so is probably adequate.
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Both the physician and the patient were blinded to the treatment. To ensure adequate blinding, SensAwake was turned ON in all devices and this setting displayed to the user."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Quote: "Both the physician and the patient were blinded to the treatment. To ensure adequate blinding, SensAwake was turned ON in all devices and this setting displayed to the user."
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Identical machine appearance unlikely to affect measurement of these outcomes.
Incomplete outcome data (attrition bias)   All outcomes	High risk	5 participants withdrew before completion of both arms. Data on machine usage available for participants who completed both arms.
Selective reporting (reporting bias)	Low risk	Outcomes reported in accordance with trial protocol.
Other bias	Low risk	No significant concerns identified.

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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	Neurocognitive function Machine usage (average hours used) Symptoms (ESS)
Funding & conflicts of interest statements	Details not available (conference abstract)
Notes	TJL wrote for confirmation of data and methods on 3 September 2008
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Quote: "Global cognitive functioning, attention, vigilance, language, memory.......were blindly assessed." No further information available to judge this
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	High risk	20% attrition. Non‐completers not analysed
Selective reporting (reporting bias)	Unclear risk	Results reported in abstract form. Not all outcomes reported
Other bias	Unclear risk	Information not available

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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 Exclusion criteria: not consenting to positive pressure device, treatment for mood disorders such as anxiety and depression
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 12 weeks
Outcomes	Machine usage (average hours used & average days used) Quality of life (SF‐36) AHI Treatment pressure
Funding & conflicts of interest statements	Funding not declared. Conflict of interest: none
Notes	Unadjusted values used in the analysis as the P values were high and errors were very small.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "We used single sequence of random assignments for randomisation." Not clear how sequence was generated.
Allocation concealment (selection bias)	Unclear risk	Quote: "There was no selection bias if the patient wanted to enrol in our study." Not clear how allocation was concealed from study personnel or participants
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study was not blinded
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study was not blinded
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: "Six of the 25 enrolled OSA patients (24%; 3 received APAP first and three received CPAP first) withdrew during the first month due to intolerance to CPAP/APAP."
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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d'Ortho 2000.

Methods	Randomised, single‐blind, cross‐over study. Method of randomisation: random sampling number tables (correspondence with trialist). All participants accounted for Data analysis: paired t test where ANOVA significant. T test used for treatment pressure. Analysis on usage 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 treatment
Interventions	Auto‐CPAP versus fixed CPAP. No washout period Study duration: 2 x 4 week treatment arms
Outcomes	Machine usage (average hours used) AHI Treatment pressure Tolerance to CPAP (questionnaire scoring system) Symptoms (ESS) Preference
Funding & conflicts of interest statements	Funded by Institut National de la sante et de la Recherche Medicale & by Nellcor‐Puritan Bennett. No declaration of interests provided.
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random sampling number tables
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Patients were not aware of the order of administration (i.e. they were blinded to the setting mode until the first night of use after which they could easily guess which mode they were using.).........The questionnaire was completed with the help of sleep laboratory technicians who were unaware of CPAP mode."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Awareness of treatment group assignment unlikely to affect objective outcome data from the study
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Patients were not aware of the order of administration (i.e. they were blinded to the setting mode until the first night of use after which they could easily guess which mode they were using.).........The questionnaire was completed with the help of sleep laboratory technicians who were unaware of CPAP mode."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Awareness of treatment group assignment unlikely to affect objective outcome data from the study
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants accounted for
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 intensive support Study duration: 9 months
Outcomes	Machine usage (hours of use and % days used) AHI Oxygen desaturation index Symptoms (ESS) Treatment pressure
Funding & conflicts of interest statements	Information not available (link to declarations of interest no longer live)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Pulling mixed and sealed envelopes"
Allocation concealment (selection bias)	Low risk	Quote: "Pulling mixed and sealed envelopes... At time of recruitment, recruiters were also unaware of allocation."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Patients were not told about their pressure mode, however, full blinding of pressure delivery was not possible. At time of recruitment, recruiters were also unaware of allocation."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Awareness of treatment group assignment unlikely to affect objective outcome data from the study
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Outcome assessors were not blinded"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	No information on withdrawals provided
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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; significant comorbidities
Interventions	CPAP with expiratory pressure relief (C‐Flex) versus fixed pressure CPAP Study duration: 24 weeks
Outcomes	Machine usage (average hours used) Treatment satisfaction (VAS) Symptoms (ESS)
Funding & conflicts of interest statements	This study was funded by Respironics. No author declarations provided.
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was centralized by the sponsor. Randomization lists were generated in block sizes of 4 and 6 randomly chosen with respect to order. 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 (selection bias)	Low risk	Quote: "Research assistants received sealed random condition assignment cards from Respironics to determine standard CPAP or C‐Flex therapy."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Participants were not made aware of the treatment they were assigned. This study was therefore a.......single‐blinded, controlled study". Only participants were blinded.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Study design unlikely to affect these outcomes.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study personnel were aware of treatment group assignment as the study was single‐blinded.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Study design unlikely to affect these outcomes.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: "Data were analyzed with multivariate mixed models procedures that allowed for analysis including participants with missing observations."
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 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 laboratory studies)
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Quality of life (SF‐36) Treatment pressure
Funding & conflicts of interest statements	Not available (conference abstract)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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Fietze 2007.

Methods	Randomised, double‐blind, parallel group study. Participants randomised for 2 night cross‐over and retained 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 excessive sleepiness at baseline also eligible if AHI > 20 Exclusion criteria: other sleep disorders (e.g. restless leg syndrome or periodic leg movement syndrome; 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) Study duration: 6 weeks
Outcomes	Machine usage (average hours used) Symptoms (ESS) Quality of life (SF‐36) AHI Treatment pressure
Funding & conflicts of interest statements	Funding quote: "This study was supported by an unrestricted grant from Respironics Inc.". No declarations reported from authors.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised but no further details provided.
Allocation concealment (selection bias)	Unclear risk	Insufficient information available to allow judgement.
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Same device used with different pressure settings (REMstar Auto CPAP).
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Same device used with different pressure settings (REMstar Auto CPAP).
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Adequate blinding procedure in place and unlikely that this has impacted on subjective outcomes.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Adequate blinding procedure in place and unlikely that this has impacted on objective outcomes.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All 21 participants who started completed the study.
Selective reporting (reporting bias)	High risk	Symptoms and quality of life data measured but reported as aggregate of two treatment groups and described as not significantly different.
Other bias	Low risk	No concerns identified.

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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 Study duration: 2 x 8 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Tolerability (leak time)
Funding & conflicts of interest statements	Not provided
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "a randomized, single‐blinded, cross‐over study." Only participants were blinded.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by open‐label design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Only participants were blinded.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by open‐label design.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Gay 2003.

Methods	Randomised, double‐blind, parallel group trial. Machines had settings: 'Set CPAP'; 'Set NBL' and 'A'. Assessors 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; residence 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
Outcomes	Machine usage (average hours used) Symptoms (ESS) AHI Tolerability Quality of life (FOSQ)
Funding & conflicts of interest statements	Quote: "Dr. Peter Gay received grant support for this study by Respironics Inc. (noted in manuscript)."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Low risk	Quote: "the technician selected the 'A' mode which in a double‐blinded and selective way, locked in the optimal settings for either CPAP or NBL"
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "the technician selected the 'A' mode which in a double‐blinded and selective way, locked in the optimal settings for either CPAP or NBL.............true identification of the 'A' mode was not revealed until the end of the trial"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by study design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "the technician selected the 'A' mode which in a double‐blinded and selective way, locked in the optimal settings for either CPAP or NBL.............true identification of the 'A' mode was not revealed until the end of the trial"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by study design.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Randomisation was performed prior to baseline PSG, after which a number of participants became ineligible. All participants recruited to the 2nd phase completed the study. There were no withdrawals from this study, although the sample reflects a selected population.
Selective reporting (reporting bias)	High risk	Data on quality of life (FOSQ) were not reported but described as 'equivalent' between two treatment arms.
Other bias	Low risk	No concerns identified

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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 Study duration: 2 x 4 weeks
Outcomes	Machine usage (average hours used) Satisfaction with therapy Symptoms (ESS)
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	TJL emailed for confirmation of methods and data on 4 September 2008
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available; requested
Allocation concealment (selection bias)	Unclear risk	Information not available; requested
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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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 Study duration: 12 weeks
Outcomes	Symptoms (ESS) Blood gases (PaO₂ and PaCO₂) Lung function
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	Unpublished conference abstract
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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Gulati 2015.

Methods	Prospective, randomised, cross‐over study in patients who were suboptimally compliant with CPAP despite 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 prescription despite technical and educational interventions, symptoms of pressure intolerance Exclusion criteria: significant airflow obstruction (FEV₁/FVC < 60%), pretreatment study showing central 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
Outcomes	Machine usage (average hours used) Symptoms (ESS) Maintenance of wakefulness test Quality of life (SAQLI) AHI Device comfort Preference
Funding & conflicts of interest statements	Funding source: not declared; conflict of interest: none
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Simple randomisation technique was used to allocate patients into different groups."
Allocation concealment (selection bias)	Low risk	Quote: "(Allocation sequence concealment) was done independently by the research and development officer, so the patients and researchers were not aware of the allocation sequence."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Neither (participants or research personnel) were blinded as the machines used were different in each arm."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Outcome assessors were not blinded to treatment allocation, but the outcomes unlikely to be affected by open‐label design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Outcome assessors were not blinded to treatment allocation
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Outcome assessors were not blinded to treatment allocation, but the outcomes unlikely to be affected by open‐label design.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "31 gave consent and were recruited. One developed a stroke during the treatment period (on Bi‐level PAP arm) and 2 others did not complete the study (one of them dropped out after first using Bi‐level PAP and the other after using the new CPAP). These subjects were excluded from the analyses."
Selective reporting (reporting bias)	Low risk	All outcomes were reported
Other bias	Low risk	No concerns identified

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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 Study duration: 12 weeks
Outcomes	Machine Usage (average hours used) Symptoms (ESS) Tolerability Withdrawals
Funding & conflicts of interest statements	Funding source: study was funded by manufacturers. Quote: "Diese Studie wurde finanziell unterstützt durch die Firmen Fisher & Paykel Healthcare und Air Products Medical GmbH" Author declaration of interests are identical to funding source
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study participants assigned according to a randomised schedule but no more detail provided about sequence of treatment group assignments
Allocation concealment (selection bias)	Unclear risk	No detail described. Insufficent information available to judge
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Identical devices provided
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	Identical devices provided
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Identical devices provided
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	Identical devices provided
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐users excluded from the analysis
Selective reporting (reporting bias)	High risk	Outcome data not available for symptoms. Objective of the study differed from that of the review question, but symptoms likely to have been collected.
Other bias	Low risk	No concerns identified

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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
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 treatment
Interventions	Auto‐CPAP versus fixed CPAP. No washout Study duration: 2 x 12 week treatment periods
Outcomes	Treatment pressure Symptoms (ESS) Machine usage (hours of usage, % nights used effectively & % days used) AHI
Funding & conflicts of interest statements	Not provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Hospital number (odd versus even last digit)
Allocation concealment (selection bias)	High risk	Study investigators likely to be aware of treatment group assignment
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study investigators likely to be aware of treatment group assignment
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by study design
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study investigators likely to be aware of treatment group assignment
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by open‐label design
Incomplete outcome data (attrition bias)   All outcomes	High risk	High withdrawal rate and non‐completers not included in analysis
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 previous 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	Symptoms (ESS) Machine usage (average hours used) Quality of life (SF‐36) Ease of use Tolerability Treatment pressure
Funding & conflicts of interest statements	Quote: "This was an industry supported study by ResMed Australia. Dr. Hukins received research equipment from ResMed Australia."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation was performed by a laboratory scientist not involved with the study using the technique of shuffled sealed envelopes containing equal numbers of each treatment arm"
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was performed by a laboratory scientist not involved with the study using the technique of shuffled sealed envelopes containing equal numbers of each treatment arm"
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "....this single‐blinded, randomised cross‐over study.......The Autoset T was used for both treatment modes in an attempt to blind the patient to the mode...Investigators were not blinded..."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by single‐blind study design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Investigators were not blinded..."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by open‐label design.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐completers not included in analysis
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 2 x 4‐week treatment periods (washout 2 weeks)
Outcomes	Machine usage (average hours used) Symptoms (ESS) AHI Treatment pressure Preference Polsomnography outcomes
Funding & conflicts of interest statements	Quote: "This study was funded by Respironics Inc., Murrysville, PA." Author conflicts of interest: not declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "...this randomized, prospective, single‐blind cross‐over trial.....Patients were unaware of the treatment mode..."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by single‐blind study design.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study personnel would have been aware of treatment group assignment.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by single‐blind study design.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Jarvis 2006.

Methods	Randomised, cross‐over study. Statistical analysis methods unclear but paired data obtained via correspondence
Participants	N = 20 participants Inclusion criteria: diagnosed with OSA; established on CPAP therapy
Interventions	Modified APAP (bi‐level pressure mode) versus fixed CPAP Study duration: 2 x 2 weeks
Outcomes	Machine usage (average hours used) AHI Treatment pressure Preference
Funding & conflicts of interest statements	Resmed sponsored the study but no other details were available.
Notes	TJL emailed for confirmation of data and methods 5 September 2008. Reply from Resmed October 2008
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The study was randomised by pulling the order of treatment received 'out of a hat'"
Allocation concealment (selection bias)	Low risk	Quote: "The person who pulled the order was a ResMed employee independent of the study and with no knowledge of the study."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All completed
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 2 x 2‐week treatment periods
Outcomes	Machine usage Sympotoms (ESS) AHI Mean pressure for treatment Quality of life (SF‐36)
Funding & conflicts of interest statements	Not available (conference abstract)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 3 to 6 weeks
Outcomes	Machine usage (average hours used and week with CPAP use > 4 hours) Treatment pressure Polysomnography (% sleep efficiency; % time awake; % sleep stage 1 and 2; % sleep stage 3 and 4 AHI Withdrawals Treatment pressure
Funding & conflicts of interest statements	Not provided
Notes	Sleep study following treatment done between 3 and 6 months
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly assigned to receive either automatically adjusting or conventional nCPAP."
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "the design of the study was single‐blinded"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "the design of the study was single‐blinded"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐completers did not contribute to the analysis (4%)
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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 initial 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 disease, 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)
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Blood pressure Quality of life (FOSQ) Withdrawals Patient preference Treatment satisfaction Treatment pressure Adverse events
Funding & conflicts of interest statements	Quote: "Philips Respironics provided funding for this study; Drs. Kushida, Berry, Blau, Fietze, Kryger, 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 support 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 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 Weinmann."
Notes	Patients in APAP group ‐ initially APAP for two weeks followed by fixed CPAP for six months
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Urn randomization was used to control for the potentially confounding variables (age, gender, education, AHI, subjective sleepiness)"
Allocation concealment (selection bias)	Unclear risk	Insufficient information to make judgement
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The Principal Investigator (PI) and research staff administering questionnaires or interacting with the participant were blinded to randomization and the results of all participant evaluations...participants were blinded to treatment"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The Principal Investigator (PI) and research staff administering questionnaires or interacting with the participant were blinded to randomization and the results of all participant evaluations"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "Fourteen participants did not receive the therapy to which they were randomized, but were included in the intention‐to‐treat analysis."
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 Exclusion criteria: severe comorbidity, such as acute or chronic heart failure (NYHA grade 3 or 4), severe COPD, dementia, alcoholism, drug abuse, and age under 18
Interventions	CPAP versus C‐Flex Study duration: 2 x 6 weeks
Outcomes	Machine usage (average hours used) Leakage Withdrawals AHI Patient preference
Funding & conflicts of interest statements	Funding quote: "This study was supported by Air Products Medical GmbH."  Conflicts of interest quote: "The authors had no conflicts of interest to declare in relation to this article."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to make judgement
Allocation concealment (selection bias)	Unclear risk	Insufficient information to make judgement
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The physicians and technicians performing the titration and scoring the polysomnographic data were blinded to the treatment mode which was chosen...The patients were only informed that they would receive two different modes of therapy, but they did not know if they got CPAP or C‐Flex"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The physicians and technicians performing the titration and scoring the polysomnographic data were blinded to the treatment mode which was chosen"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "Twelve patients dropped out of the study (7 after C‐Flex, 5 after CPAP); 4 of them gave up the therapy completely (2 after CPAP, 2 after C‐Flex)"
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 Study duration: 4 weeks
Outcomes	Machine usage Symptoms (ESS) Quality of life (FOSQ)
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	Unpublished conference abstract. Details requested by email
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available; requested
Allocation concealment (selection bias)	Unclear risk	Information not available; requested
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available; requested
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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Marrone 2004.

Methods	Randomised, single‐blind, cross‐over study. Method of randomisation: not described. Statistical analysis: 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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 2 x 4 weeks. No washout described
Outcomes	Machine usage (average hours used, nights used effectively & frequency of use as % days)) Symptoms (ESS) Treatment pressure Preference
Funding & conflicts of interest statements	Funding quote: "This study was supported by Air Products Medical GmbH."  Conflicts of interest quote: "The authors had no conflicts of interest to declare in relation to this article."
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Machines were assigned in a single blind, random fashion."
Allocation concealment (selection bias)	High risk	Given that the study was single‐blind, the pressure setting of the machines may have been known by investigators
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed the study
Selective reporting (reporting bias)	Unclear risk	No information available
Other bias	Low risk	No concerns identified

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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 Study duration: 4 weeks
Outcomes	Machine usage (average hours used) Symptoms (ESS)
Funding & conflicts of interest statements	Quote: "None of the authors have had any financial relationships with Respironics Inc., who are the 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The sequence of allocation to treatment was determined by sleep technicians randomly picking one of a set of pre‐prepared opaque envelopes containing the treatment allocation."
Allocation concealment (selection bias)	Low risk	Quote: "An urn with 2 differently coloured paper clips was prepared. One clip 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 and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Study personnel would have been aware of treatment group allocation.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Measurements of sleepiness and reaction times were undertaken by an investigator blinded to treatment allocation; patients were blinded to treatment allocation."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group allocation
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "Whilst all 19 patients were included in the primary analysis under the intention‐to‐treat principle due to missed appointments only 17 patients are included in the Epworth analysis." This is a low rate of attrition.
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 restless leg syndrome); correctly executed 30‐minute CPAP/NIV test 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 saturation 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.
Outcomes	Machine usage (average hours used) Blood gas (PaCO₂ at 3 months) Cardiovascular markers (HbA1C, Lipid profile) Quality of life (FOSQ) Symptoms (ESS) Nocturnal oximetry AHI Adverse events
Funding & conflicts of interest statements	Quote: "Supported by the Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo) grant PI050402, the Spanish Respiratory Foundation 2005 (FEPAR), and Air Liquide 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: participants "randomized by an electronic database (simple randomization)."
Allocation concealment (selection bias)	Unclear risk	Insufficient information available to judge.
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	For most outcomes of interest to the review open‐label nature of the study places the study at high risk of performance bias.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	For most outcomes of interest to the review open‐label nature of the study places the study at high risk of detection bias.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	10% of participants missing data at 2 months. ITT was undertaken with missing data imputed for secondary outcomes (quote): "following a multiple imputation method with iterative multivariable regression, because the missing data had characteristics compatible with a missing at random pattern."
Selective reporting (reporting bias)	Low risk	Outcomes of interest reported in accordance with trial registry record.
Other bias	Low risk	No other sources of bias identified.

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Massie 2003.

Methods	Randomised, single‐blind, cross‐over study. Methods of randomisation not reported. Comparisons between 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 apnoeas/hr; patients taking medication considered to interfere with sleep respiration
Interventions	Auto‐CPAP versus fixed CPAP. No washout period Study duration: 2 x 6‐week treatment periods
Outcomes	Machine usage (average hours used and % days used) Treatment pressure AHI Quality of life (SF‐36 score reported by domain) Symptoms (ESS and sleep diary score)
Funding & conflicts of interest statements	Supported by a grant from ResMed Corporation. One of the authors (Neil Douglas) declared a role as medical advisor to ResMed
Notes	Participants aware that machine usage was monitored; stipend offered for completion of study
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: ".....randomised, single‐blinded, cross‐over study....(patients) were not informed of the type of therapy they were receiving"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single blind study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Low rate of non‐completers excluded. One excluded from study and additional participant excluded from analysis of machine usage due to unreadable data.
Selective reporting (reporting bias)	Unclear risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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) Exclusion criteria: not reported
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 3 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Withdrawals
Funding & conflicts of interest statements	Not provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers table
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Participants unaware as to group they were randomised to (CPAP machines were identical).
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Participants unaware as to group they were randomised to (CPAP machines were identical).
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed the study
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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
Interventions	Four auto‐CPAP machines assessed: GK 418 P, 3.1 version AutoSet Spirit, 302 version PV 10I, firmware 0.92 version Somnosmart 1, 2.02 version All 4 compared against fixed pressure CPAP Study duration: 24 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Withdrawals Quality of life (SF‐36)
Funding & conflicts of interest statements	Not provided
Notes	Data aggregated from 4 auto‐CPAP groups
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The randomisation was carried out centrally..."
Allocation concealment (selection bias)	Low risk	Quote: "...randomly coded envelopes opened by a coordinator from envelopes batched for each centre in order to have similar proportions of patients in each group from each centre."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Participants who withdrew were not included in the analysis
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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
Outcomes	Machine usage (average hours used) Treatment pressure AHI Quality of Life (FOSQ) Epworth Sleepiness Scale Preference
Funding & conflicts of interest statements	Not available (conference abstract)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blinded study
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	No information available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blinded study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	No information available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available
Selective reporting (reporting bias)	Unclear risk	No information available. Information only available as a conference abstract. No further details about the study are available.
Other bias	Unclear risk	No information available

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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 Study duration: 2 x 2 weeks
Outcomes	Machine usage (average hours used)
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "A randomized two‐arm prospective crossover unblinded....."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "A randomized two‐arm prospective crossover unblinded....."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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Muir 1998.

Methods	Randomised, double‐blind, cross‐over study. Method of randomisation not reported. Statisitical analysis 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 Study duration: 2 x 8‐week treatment periods 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)
Outcomes	Machine usage Adverse events Preference
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	Study published as conference abstract
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Quote: "Double‐blind, crossover study". No further information available.
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	We have judged the risk of bias on objective outcomes to be unclear in the absence of more detail beyond the study being double‐blind.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Quote: "Double‐blind, crossover study". No further information available.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	We have judged the risk of bias on objective outcomes to be unclear in the absence of more detail beyond the study being double‐blind.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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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)
Outcomes	Machine usage (average hours used) ESS Upper airway symptoms Preference
Funding & conflicts of interest statements	Quote: "This study was funded by an Otago University Research Grant." Author declarations not provided (conference abstract)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The authors attempted to create a placebo humidification arm in which the HC100 was used without the heating unit turned on.........An investigator blinded to research treatment interviewed the patients at the end of each treatment arm..."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "An investigator blinded to research treatment interviewed the patients at the end of each treatment arm..."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐completers excluded from analysis
Selective reporting (reporting bias)	Unclear risk	Not possible to determine based on details provided
Other bias	Low risk	No concerns identified

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Nilius 2006.

Methods	Randomised, parallel group trial
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 Study duration: 7 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS)
Funding & conflicts of interest statements	Quote: "This study was financed by a gift from Heinen U. Lowenstein. Dr. Ruhle has received research 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 ACCP 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available; requested
Allocation concealment (selection bias)	Low risk	Third party responsible for randomisation and setting machines to relevant treatment mode
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The patients were informed that they would receive two different forms of treatment .....but were given no further details...........The technician had no information from the investigators about the modality that the patients were receiving"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The physician and technicians reviewing the polysomnographic data and performing the manual CPAP titration were blinded to the treatment mode employed"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants accounted for in analysis
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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) Exclusion criteria: not reported
Interventions	Auto‐CPAP versus fixed pressure CPAP Study duration: 2 x 8‐week treatment periods
Outcomes	Machine usage (average hours used and % days used) Symptoms (ESS) AHI Preference
Funding & conflicts of interest statements	Quote: "This was not an industry supported study. Drs. Nolan, Doherty, and Mc Nicholas have indicated no financial conflicts of interest."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Low risk	Quote: "An independent person not involved in the study design, protocol, or analysis assigned the devices to the patients in random order."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "....patients were not informed about the different technologies used in the devices.....the trial was fully blinded to the investigator performing the analysis."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "...the trial was fully blinded to the investigator performing the analysis."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	High rate of participants not crossing over on to subsequent treatment arm
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 abnormality; 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 Study duration: 2 x 8‐week treatment periods
Outcomes	Machine usage (nights used effectively) Symptoms (ESS) Preference Treatment pressure Self‐estimated sleep latency
Funding & conflicts of interest statements	Not provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation tables
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: ".....single‐blind, randomized, crossover trial........subjects were told that they would sleep with the machine functioning in two distinct modes.....no further explanation was given."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind nature of the study means that these outcomes are at risk of bias
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Rate of participants not crossing over could be high enough to introduce bias
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Nussbaumer 2006.

Methods	Randomised, cross‐over study. Double‐blinding: investigators and participants unaware as to treatment. 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
Interventions	Auto‐CPAP versus fixed CPAP No washout period described Study duration: 2 x 4‐week treatment periods
Outcomes	Machine usage (average hours used and % nights used > 4 hours) Symptoms (ESS) AHI Quality of life (SF‐36) Treatment pressure Preference
Funding & conflicts of interest statements	Quote: "Study supported by MADELA AG, distributors of Respironics products in Switzerland". No author conflicts provided.
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Treatments given in "random order"
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Patients and attending physicians were blinded to treatment modes and order of application."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "attending physicians were blinded to treatment modes and order of application."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐completers excluded from the analysis (N = 8)
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Patruno 2007.

Methods	Randomised, parallel group trial
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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 12 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS) Blood pressure
Funding & conflicts of interest statements	Quote: "This work was supported by a University of Milan Fondo Interuniversitario per la Ricerca Scienfifica 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 conflicts of interest to disclose."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "After CPAP titration, all subjects were randomised to receive either fixed‐level CPAP for 3 months."
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	40 participants recruited; 9 withdrew (no information on which groups they were assigned to); 3 of these participants withdrew due to poor compliance
Selective reporting (reporting bias)	High risk	Data on ESS not presented: requested from authors along with details of randomisation and withdrawals
Other bias	Low risk	No concerns identified

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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 attempted 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	Machine usage (average hours used and N using it effectively) Symptoms (ESS and Fatigue Severity Scale) Quality of life (FOSQ) Withdrawals
Funding & conflicts of interest statements	Quote: "This study was supported by a grant from Phillips Respironics. Dr. Powell has received research support from Philips Respironics, Inc, Fisher – Paykel Healthcare, and Takeda Pharmaceuticals Dr. Malhotra 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 support 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Urn randomization was used for treatment group placement using the variables of gender, age, diagnostic AHI, and education"
Allocation concealment (selection bias)	Low risk	Quote: "Urn randomization was used for treatment group placement using the variables of gender, age, diagnostic AHI, and education"
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The participant, investigator, respiratory therapist, and research staff were all blinded to the therapy group"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The participant, investigator, respiratory therapist, and research staff were all blinded to the therapy group"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "A total of 48 participants were randomized into the trial......A total of 48 participants were analyzed for the primary endpoint on an intent‐to‐treat basis"
Selective reporting (reporting bias)	High risk	Study protocol indicates that AHI was measured but this was not reported in main trial publication.
Other bias	Low risk	No concerns identified

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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 Study duration: 3 months
Outcomes	Machine use (average hours used) Quality of life (SF‐36 and Grenoble SAQOL) Tolerability Withdrawals Symptoms (ESS)
Funding & conflicts of interest statements	Quote: "This work was supported by grants from 'Comite ´ National des Maladies Respiratoires' and Respironics. Author conflicts not reported."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	'Randomization was performed by a computer‐generated schedule in random blocks of six and was stratified according to study centers'
Allocation concealment (selection bias)	Low risk	'Randomization was performed by a computer‐generated schedule in random blocks of six and was stratified according to study centers'
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	'Patients were not aware of whether they were receiving CPAP with or without C‐Flex activated'.........'The investigators who assessed outcome were unaware of the randomization status of the patients'
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	'The investigators who assessed outcome were unaware of the randomization status of the patients and did not set up or maintain the machines'
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	'The data for all outcomes were analyzed on an intention‐to treat basis'. Balanced but high rates of withdrawal. Reasons for withdrawal include refusal to continue with treatment
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 claiming 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, patients in hospital, patients included in another clinical study
Interventions	Fixed versus auto‐CPAP Study duration: 4 months
Outcomes	Machine usage (average hours used and N using > 4 hours per night) Symptoms Blood pressure Withdrawals Quality of life (SF‐36)
Funding & conflicts of interest statements	Quote: "The study was funded by the Fondation Agir pour les maladies chroniques. The corresponding 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation was conducted by...a computer‐generated random numbers list (six patients per block)."
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was conducted by telephone call to a clinical trials statistician, independent of the study..."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "All patients, investigators and outcome assessment technicians were blinded to the arms to which the patients were allocated."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "All patients, investigators and outcome assessment technicians were blinded to the arms to which the patients were allocated."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	High and imbalanced rate of withdrawal between intervention groups. Multiplie imputation method used to replace missing values from ITT analysis.
Selective reporting (reporting bias)	High risk	Quality of life, as measured by SF‐36 was described as not different between the two arms. The trial registry record indicated that symptoms was also measured but this was not reported in the trial publication.
Other bias	Low risk	No concerns identified

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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 Study duration: 2 x 6‐week treatment periods 24‐hour telephone helpline was at the disposal of the participants
Outcomes	Machine usage (average hours used) AHI Arousals Treatment pressure Preference
Funding & conflicts of interest statements	Quote: "The devices were supplied by the Weinmann Company, Hamburg, Germany." No author conflicts provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Low risk	Quote: "Only the person who managed the randomisation knew about the order of the treatment modes in the individual patients. This person adjusted the devices to the different treatment modes."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Those who did the questioning and cared for the patients in the hospital and sleep laboratory and those who evaluated results of PSG were blinded to the mode of treatment applied.........The patients were not informed about the sequence in which the two treatment modes were applied."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Those who did the questioning and cared for the patients in the hospital and sleep laboratory and those who evaluated results of PSG were blinded to the mode of treatment applied."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	5/52 participants withdrew; their data were excluded from analysis
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Reeves‐Hoché 1995.

Methods	Randomised, parallel group trial
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 illness; pregnancy
Interventions	Bi‐PAP versus CPAP administered at home Study duration: 52 weeks Prescribed inspiratory pressure was 11 mmHg ± 0.3 and expiratory pressure was 7 mmHg ± 0.3 in the BiPAP group versus 10 mmHg ± 0.2 in the fixed CPAP group at baseline
Outcomes	Machine usage Withdrawals Tolerability
Funding & conflicts of interest statements	'Supported in part by Respironics'. Author conflicts not provided.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated numbers
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Non‐completers did not contribute to analysis
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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) Exclusion criteria: not reported
Interventions	Auto‐CPAP versus fixed pressure CPAP. CPAP titration undertaken manually in sleep laboratory Study duration: 4 weeks
Outcomes	Machine usage ESS AHI
Funding & conflicts of interest statements	Not provided
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised; other information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "...random, single‐blind fashion..."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed the study
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 Exclusion criteria: not reported
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
Outcomes	Machine usage (average hours used) Symptoms (ESS) AHI Quality of life (FOSQ) Satisfaction
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	Study available as conference abstract
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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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, facial/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	Treatment pressure Symptoms (ESS) AHI Preference
Funding & conflicts of interest statements	Not available (conference abstract)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "By block randomisation of a statistical program (Randomisation program BSR, Windows version 5.0) with a block size of 4‐4‐8"
Allocation concealment (selection bias)	Low risk	Quote: "Both the patient and the person who recruited the participants were unaware of the allocation sequence."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "The trial was fully blinded to the patients. It was not possible to fully blind the investigator performing the analysis."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "It was not possible to fully blind the investigator performing the analysis...The registered technologists were not aware of the group allocation of the patients. However they could deduct therapy as the PAP‐pressure was recorded during the sleep study."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	In both groups 3 drop‐outs occurred. 17 subjects completed 6 weeks of CPAP with subsequently 6 weeks of RAPAP and 16 subjects completed 6 weeks of RAPAP with subsequently 6 weeks of CPAP.
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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 Study duration: 2 x 4‐week treatment periods
Outcomes	Machine usage (average hours used) Treatment pressure Patient preference AHI
Funding & conflicts of interest statements	Not available (conference abstract)
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Unclear risk	Information not available
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Unclear risk	Information not available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Information not available
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Unclear risk	Information not available

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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 Study duration: 2 x 4 weeks
Outcomes	Machine usage (average hours used) Tolerability
Funding & conflicts of interest statements	Quote: "K‐H. Ruhle and G. Nilius received research funding from Fisher & Paykel Healthcare, Heinen 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
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The study had a randomised, cross‐over design and used a previously prepared randomisation list.
Allocation concealment (selection bias)	Low risk	Quote: "The patients were told about the group allocation only after consent. The recruiting doctor was blinded to the randomisation."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "However, it must be kept in mind that patients knew when cHH was used and this may impact on the reported symptoms"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "The outcome assessor who calculated the study results was not blinded to the allocation."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: "Fifty one patients were recruited, 7 dropped out during the course of the study, of which 5 were allocated to the humidification group and 2 in the CPAP group.....44 patients completed the study."
Selective reporting (reporting bias)	Low risk	All outcomes were reported
Other bias	Low risk	No concerns identified

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Ryan 2009.

Methods	Randomised, parallel group trial
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 breathing 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 Study duration: 4 weeks
Outcomes	Machine usage (average hours used and % nights used) Quality of life (SF‐36) Symptoms (ESS) Tolerability (nasal symptoms measured by MiniRQLQ)
Funding & conflicts of interest statements	Quote: "This was not an industry supported study. The authors have indicated no financial conflicts of interest."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation was used to randomise patients to different treatment groups
Allocation concealment (selection bias)	Low risk	Randomisation occurred centrally
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "However, patients were not blinded, since blinding would be difficult to achieve and requiring the use of placebo humidification, which has also been a limitation of previous studies."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Although the investigators administering questionnaires and downloading data from the devices were blinded to the treatment arm, participants rating symptoms and other subjective outcomes would have been aware of the treatment group.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: "All analyses were undertaken using the intention‐to‐treat principle" Quote: "Of the 123 patients participating in the study, 112 subjects (91%) completed the trial... Of the 10 patients wishing to discontinue  CPAP, 5 were randomized to dry treatment, 2 were commenced on additional 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.
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 snoring + flow limitation) versus fixed CPAP Study duration: 2‐week run‐in with either auto‐CPAP device. 3 x 4 week treatment periods.
Outcomes	Machine usage (average hours used) Quality of life (SF‐36: vitality subdomain) Symptoms (ESS) Sleep latency AHI Treatment pressure
Funding & conflicts of interest statements	Quote: "Supported by the Lung League of Zurich, Lung League of Schaffhausen, Lamprecht AG & Labhardt AG". Author conflicts not provided.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised; no other information available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind, cross‐over study. Quote: "Patients...... were blinded to exact study purpose and treatment modes."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Low attrition rate (2 participants/31); reasons for missing data given as lack of time (N = 1), and moving away from area (N = 1)
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 humidification during split‐night study
Interventions	CPAP with heated humidification versus conventional CPAP alone Study duration: 2 x 4 weeks
Outcomes	Machine usage (average hours used) AHI Tolerability (mask leak) Symptoms (ESS) Quality of life (FOSQ)
Funding & conflicts of interest statements	Quote: "This work was supported by the Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University. All CPAP machines and related equipment were sponsored by Fisher and Paykel Healthcare 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 disclosed no conflicts of interest."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Subjects were randomly assigned by bloc sizes of 4 to receive CPAP with or without heated humidification". Insufficient information available.
Allocation concealment (selection bias)	Low risk	Quote: "The randomisation sequence was based on the random order which was in the sealed envelope prepared by our research statistician and the investigators who conducted the study and the patients were not aware of."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "Single blind randomized cross‐over study......the subjects were blinded to the treatment arm."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study design
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Twenty‐two were subjects enrolled.....Quote: "2 more subjects dropped out from the study in the first week after CPAP use, and the reasons for dropout were CPAP refusal." Rate of withdrawal could potentially have influenced some outcomes
Selective reporting (reporting bias)	Low risk	All outcomes reported (quality of life and AHI reported as medians so could not be used in meta‐analysis)
Other bias	Low risk	No concerns identified

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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 Exclusion criteria: life‐threatening OSA (severe hypersomnolence); OSA associated with non‐obstructive 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 (effective pressure estimated by prespecified formula) versus fixed CPAP. Data entered from Auto‐CPAP 1. Study duration: 3 weeks
Outcomes	Machine usage (average hours used and N participants using machine for > 4 hours) Sleep architecture AHI Symptoms (ESS) Arousals Withdrawals Treatment pressure
Funding & conflicts of interest statements	Funded in part by Pierre Medical France. Author declarations not provided
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers table (block of 3)
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Single‐blind study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed the study
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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Sériès 2001.

Methods	Randomised, parallel group trial
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 Study duration: 3 weeks
Outcomes	Machine use (average hours used) Symptoms (ESS) AHI Withdrawals
Funding & conflicts of interest statements	Not provided
Notes	TJL emailed for details of randomisation and outcome data 8 September 2008.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random sequence
Allocation concealment (selection bias)	Low risk	Quote: "This was done using a binary randomisation list provided by our statistician who was not involved in the study."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Some participants had previously participated in a study and could have become aware of different devices irrespective of masking treatment group assignment
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Some participants had previously participated in a study and could have become aware of different devices irrespective of masking treatment group assignment
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Most outcomes in this review unaffected by the following exclusions: Quote: "The sleep stage‐ and body position‐dependence could not be characterized in 15 patients who did not change body position or whose sleep architecture 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."
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Teschler 2000.

Methods	Randomised, double‐blind, cross‐over study Two‐factor repeated measures analysis of variance (AVOVA). Order of testing (fixed CPAP versus auto‐CPAP first) taken as one fixed factor, mode of treatment (fixed CPAP versus auto‐CPAP as second factor)
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
Interventions	Auto‐CPAP versus fixed CPAP. No washout period Study duration: 2 x 8‐week treatment periods
Outcomes	Machine usage (average hours used and % days CPAP used) AHI Tolerability (leak > 0.4 L/sec) Treatment pressure
Funding & conflicts of interest statements	Not provided
Notes	—
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised; no other information available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The staff were blinded as to whether the machine was in auto or conventional mode. Patients were not told in which mode the machine was operating."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Study had double‐blind design.
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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
Interventions	Auto‐CPAP versus fixed CPAP Study duration: 2 x 8 weeks (washout: 1 week)
Outcomes	Machine usage (average hours used) Symptoms (ESS) AHI Quality of life (SAQLI) Preference
Funding & conflicts of interest statements	Quote: "The authors declared no conflict of interest between ResMed Company and the participating institutions, which received no external funding support for this study."
Notes	TJL emailed for clarification of data from study author
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned by random table allocation into one of the two arms of the study."
Allocation concealment (selection bias)	Low risk	Quote: "Randomization was performed by an investigator external to the trial. The sequence of treatment group assignment was concealed from investigators conducting the screening and ongoing assessments.
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Open‐label study
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Open‐label study
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Low rate of exclusions from the analysis (N = 2)
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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 Study duration: 2 x 6 weeks
Outcomes	Machine usage (average hours used) Symptoms (ESS) QoL (SF‐36) Sleep latency Withdrawals Tolerablity Preference
Funding & conflicts of interest statements	Quote: "This study was supported by a grant from ResMed, Poway, CA. Dr. Douglas is a shareholder in 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomized...using a randomization schedule of balanced blocks..."
Allocation concealment (selection bias)	Low risk	Quote: "Patients were randomized...by a worker otherwise uninvolved in the trial."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "Patients were informed that 2 different methods of giving CPAP were to be assessed, but were not told which was the new method" Quote: "None of the staff involved in data acquisition or analysis were aware of the mode of treatment the patient was receiving"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The blinded staff member conducted the follow‐up assessments unaware of the type of CPAP the patient was using at the time of assessment."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: "Nineteen patients did not complete the study; at the time of dropout 9 of these were receiving fixed and 10 variable pressure CPAP" Balanced drop out which could impact on machine usage and symptoms
Selective reporting (reporting bias)	High risk	Side effects were rated by the Edinburgh questionnaire but not reported.
Other bias	Low risk	No concerns identified

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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 Study duration: 2 x 6 weeks
Outcomes	Machine usage (average hours used) AHI Symptoms (ESS)
Funding & conflicts of interest statements	Not provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not available
Allocation concealment (selection bias)	Unclear risk	Information not available
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "....randomised, single‐blinded cross‐over study"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "...single‐blinded cross‐over study"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants completed
Selective reporting (reporting bias)	Unclear risk	Information not available
Other bias	Low risk	No concerns identified

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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 pressure at the level of 95th centile pressure from the auto‐CPAP week data. Study duration: 24 weeks
Outcomes	Machine usage (average hours used) Symptoms (ESS) Quality of life (SF‐36 and SAQLI) Treatment pressure AHI Withdrawals
Funding & conflicts of interest statements	Quote: "ResMed UK provided part financial support for the purchase of CPAP machines for the study but was not involved in its design or analysis. D Jones was supported in part by a Helen Bearpark Scholarship 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated schedule (MINIM)
Allocation concealment (selection bias)	Low risk	Quote: "...investigators carrying out the assessment studies were blind to their group allocation."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "The patients and the investigators carrying out the assessment studies were blind to their group allocation."
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	Low risk	Quote: "...the investigators carrying out the assessment studies were blind to their group allocation."
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Nine participants lost to follow‐up or excluded from the analysis: Quote: "No data were entered for those who did not attend."
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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Worsnop 2010.

Methods	Randomised, parallel group study
Participants	N = 54 participants (43 M/11 F). Mean age 55 years; AHI 46. ESS 14 Consecutive OSA patients referred for CPAP, under a program paid for by the Victorian State government, were enrolled.
Interventions	Fixed pressure CPAP + humidification versus fixed pressure CPAP alone Study duration: 12 weeks
Outcomes	Machine usage (average hours used) Quality of life (SF‐36) Symptoms ESS Tolerability (Nasal symptoms & resistance)
Funding & conflicts of interest statements	Quote: "Fisher and Paykel Healthcare, Auckland, New Zealand funded this study. They were not involved 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*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation was concealed using a statistical randomisation package so that each subject was randomised to receive either treatment independently of the other subjects."
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was concealed using a statistical randomisation package..."
Blinding of participants and personnel (performance bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "It was not possible to blind patients to the type of treatment they were getting"
Blinding of participants and personnel (performance bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Blinding of outcome assessment (detection bias)   Machine usage, symptoms, quality of life, withdrawal, adverse effects	High risk	Quote: "The one CPAP therapist saw each patient at each visit. It was not possible to blind her to the treatment that the patients were getting, but she was instructed not to make any attempts to determine what type of pump each patient was using, and to try to treat each patient in a similar manner"
Blinding of outcome assessment (detection bias)   AHI, blood pressure, treatment pressure	Low risk	These outcomes unlikely to be affected by awareness of treatment group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "All of the fifty‐four subjects completed the study"
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	No concerns identified

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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; SaO_2: 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
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
Ficker 1998	Laboratory‐based study
Ficker 2000	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
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
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 humidification
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 titration 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
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 educational 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 pressure CPAP
Taylor 2003	Assessment of telemedicine intervention
Torvaldsson 2003	Inadequate duration (2 x 1 week treatment arms)
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

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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; previous 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	CPAP with humidification CPAP without humidification Study duration: 4 weeks per treatment period
Outcomes	Nasal and pharyngeal symptoms Mask leak Quality of life (FOSQ) Sleepiness (ESS) Machine usage
Notes

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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
Outcomes	Machine usage ESS AHI Treatment pressure 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 publication date 2nd quarter 2019.

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Zamora 2019.

Methods	Part of large adherence trial
Participants
Interventions
Outcomes
Notes	Conference abstract

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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 pillow mask, AHI or RDI of > 20 events per hour
Interventions	Standard CPAP device or Rest‐Activity‐Cycle (RACer) system used with positive airway pressure device (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 between arms.
Outcomes	Machine usage each night averaged over last two weeks of treatment period AHI Symptoms (ESS) Quality of life (SF‐36 questionnaire) Comfort of each device assessed by in‐house questionnaire
Starting date	20/09/2017
Contact information	Dr Angela Campbell WellSleep University of Otago, Wellington 98 Churchill Drive Crofton Downs, 6035 Wellington
Notes

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ACTRN12618000379213p.

Trial name or title	Auto‐titrating versus fixed continuous positive airway pressure in obesity hypoventilation syndrome
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 Study duration: 12 weeks
Outcomes	PaCO₂ at 3 months Cardiovascular markers (HbA1C, Lipid profile, Quality of life (FOSQ) Sleepiness (ESS) Nocturnal oximetry Machine usage AHI 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

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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

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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 (CPAP_Flex) Treatment arms scheduled to last for 4 weeks in published protocol (9 weeks according to CT.gov record)
Outcomes	Machine usage taken as average over last 2 weeks of treatment AHI Symptoms (ESS) Quality of life (SAQLI) Treatment satisfaction Treatment pressure
Starting date	December 2012
Contact information
Notes

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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 comorbidity
Interventions	Fixed CPAP versus auto‐CPAP Study duration: 4 weeks
Outcomes	Sympathetic tone measured (muscle sympathetic neural activity) Blood pressure Heart rate Catecholamine levels
Starting date	1 March 2018
Contact information	Renaud Tamisier, MD, PhD University Hospital Grenoble France
Notes

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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

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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

Differences between protocol and review

For the 2019 update of the review we have identified the following additional comparisons of interest.

Automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp) versus fixed CPAP
Automatically adjusting bilevel positive airway pressure (auto bi‐PAP) versus fixed CPAP.
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:

population ‐ male versus female;
baseline AHI > 20 versus < 20 per hour;
study quality ‐ high versus low (based upon the allocation concealment scores);
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 Table 1).

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.

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.

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.

Declarations of interest

Barry Kennedy: none known

Toby Lasserson is employed by Cochrane.

Dariusz Wozniak: none known

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.

These authors contributed equally to this work

New search for studies and content updated (conclusions changed)

References

References to studies included in this review

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Massie 2003 {published and unpublished data}

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Modrak 2007 {published data only}

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Muir 1998 {unpublished data only}

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Neill AM, Wai HS, Bannan SPT, Beasley CR, Weatherall M, Campbell AJ. Humidified nasal continuous positive airway pressure in obstructive sleep apnoea. European Respiratory Journal 2003;22(2):258‐62. [DOI] [PubMed] [Google Scholar]

Nilius 2006 {published data only}

Nilius G, Happel A, Domanski U, Ruhle KH. Pressure‐relief continuous positive airway pressure vs constant continuous positive airway pressure: a comparison of efficacy and compliance. Chest 2006;130(4):1018‐24. [DOI] [PubMed] [Google Scholar]

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Noseda A, Kempenaers C, Kerkhofs M, Braun S, Linkowski P, Jann E. Constant versus auto‐continuous positive airway pressure in patients with sleep apnea hypopnea syndrome and a high variability in pressure requirement. Chest 2004;126(1):31‐7. [DOI] [PubMed] [Google Scholar]

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Reeves‐Hoché MK, Hudgel DW, Meck R, Witteman R, Ross A, Zwillich CW. Continuous versus bilevel positive airway pressure for obstructive sleep apnea. American Journal of Respiratory Critical Care Medicine 1995;151:443‐9. [DOI] [PubMed] [Google Scholar]

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Resta O, Carratu P, Depalo A, Giliberti T, Ardito M, Marrone O, et al. Effects of fixed compared to automatic CPAP on sleep in Obstructive Sleep Apnoea Syndrome. Monaldi Archives of Chest Disease 2004;61(3):153‐6. [DOI] [PubMed] [Google Scholar]

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Teschler 2000 {published data only}

Teschler H, Wessendorf TE, Farhat AA, Konietzko N, Berthon‐Jones M. Two months auto‐adjusting versus conventional nCPAP for obstructive sleep apnoea syndrome. European Respiratory Journal 2000;15(6):990‐5. [DOI] [PubMed] [Google Scholar]

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To KW, Chan WC, Choo KL, Lam WK, Wong KK, Hui DS. A randomized cross‐over study of auto‐continuous positive airway pressure versus fixed‐continuous positive airway pressure in patients with obstructive sleep apnoea. Respirology 2008;13(1):79‐86. [DOI] [PubMed] [Google Scholar]
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Vennelle 2010 {published and unpublished data}

Vennelle M, White S, Riha RL, Mackay TW, Engleman HM, Douglas NJ. Randomized controlled trial of variable‐pressure versus fixed‐pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). Sleep 2010;33(2):267‐71. [PUBMED: 20175411] [DOI] [PMC free article] [PubMed] [Google Scholar]

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Chervin 1997 {published data only}

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References to studies awaiting assessment

Boyer 2019 {published data only}

Study to predict the benefits of first‐line humidification use and comparison of the effect of ThermoSmart™ and no humidification on adherence. clinicaltrials.gov/ct2/show/study/NCT01742949 (first received 6 December 2012).
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PERMALINK

Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea

Barry Kennedy

Toby J Lasserson

Dariusz R Wozniak

Ian Smith

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

1. Table of devices.

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

2.4. Analysis.

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Rating the certainty of evidence

Results

Description of studies

Results of the search

1.

Included studies

Study design

Participants

2. Summary of study and participant characteristics at baseline.

Interventions

Automatically adjusting CPAP (auto‐CPAP)

Bilevel positive airway pressure (Bi‐PAP)

CPAP with expiratory pressure relief (CPAPexp)

Heated humidification plus fixed CPAP

Multimodality devices

Automatically adjusting CPAP with expiratory pressure relief (auto‐CPAPexp)

Bi‐PAP with expiratory pressure relief (Bi‐PAPexp) and auto Bi‐PAPexp

CPAPexp with wakefulness detection

Outcomes

Excluded studies

Risk of bias in included studies

2.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Auto‐CPAP compared to fixed CPAP for sleep apnoea in adults.

Summary of findings 2. Bi‐PAP compared to fixed CPAP for sleep apnoea in adults.

Summary of findings 3. CPAP with expiratory pressure relief compared to fixed CPAP for adults with obstructive sleep apnoea.

Summary of findings 4. Heated humidification + fixed CPAP compared to fixed CPAP alone in adults with obstructive sleep apnoea.

Automatically adjusting continuous positive airway pressure (auto‐CPAP) versus fixed continuous positive airway pressure (fixed CPAP)