The effect of surgical weight loss on obstructive sleep apnoea: A

systematic review and meta-analysis

SUPPLEMENTARY DATA

Ai-Ming Wong1,2, Hayley N. Barnes3, Simon A. Joosten1,2, Shane A. Landry4, Eli Dabscheck3,5, Darren R. Mansfield1,6, Shyamali C. Dharmage7, Chamara V. Senaratna7,8, Bradley A. Edwards4*, Garun S. Hamilton1,2*

*These authors jointly supervised this work.

1Monash Lung and Sleep, Monash Health, Monash Medical Centre, Melbourne, Australia, 2School of Clinical Sciences, Monash

University, Melbourne, Australia, 3Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne

Victoria 3004, Australia, 4Department of Physiology and School of Psychological Sciences, Monash University, Melbourne,

Australia, 5Central Clinical School, Monash University, Melbourne, Australia, 6School of Psychological Sciences and Monash

Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria, Australia, 7Allergy and Lung Health Unit, Centre

for Epidemiology & Biostatistics, Melbourne School of Population & Global Health, Victoria 3010, Australia, 8University of Sri

Jayewardenepura, Nugegoda, Sri Lanka.

- Running Head: “Effect of surgical weight loss on OSA”

- Word count: 3904

- Corresponding Author:

Associate Professor Garun HamiltonMonash Lung and Sleep, Monash Medical Centre, 246 Clayton Road,Clayton 3168, Victoria, AustraliaPh: +61 3 95946666Fax: +61 3 95946811Email: garun.hamilton@monashhealth.org

SUPPLEMENTARY RESULTS

Additional results from the systematic review

There were a number of interesting observations upon reviewing the 27 studies included in

the systematic review which were not able to be covered in the main manuscript due to

limited space. Hence, we present some of the interesting results in this section, focussing in

particular on: a) surgical vs non-surgical weight loss interventions in non-randomised

controlled trials (non-RCTs), b) positional obstructive sleep apnoea (OSA), and c) impact of

gender on OSA in participants undergoing bariatric surgery.

a) Non-RCTs comparing surgical and non-surgical weight loss interventions

One non-RCT comparing the effects of surgical weight loss (gastric banding or gastric

bypass) with continuous positive airway pressure (CPAP) reported a greater reduction in

median apnoea-hypopnoea index (AHI) and body mass index (BMI) in the bariatric surgery

group [1]. The surgical group had a significant reduction in median BMI (from 43.7 kg/m² to

28.3 kg/m²) over 12 to 18 months compared with the CPAP group (from 33.8 kg/m² to 34.2

kg/m²), and the AHI also improved in the surgical group (from 18.1 events/h to 6.5 events/h).

The AHI reported in the CPAP group was performed with CPAP, showing a significant

reduction from baseline (from 36.5 to 3.8 events/h).

Another non-RCT [2] comparing the effects of surgical weight loss (Roux-en-Y gastric

bypass [RYGB]) with an intensive lifestyle intervention (participants underwent a one-year

lifestyle program at a rehabilitation centre) showed that RYGB was more effective at

reducing the severity of OSA with a mean between-group difference AHI of 7.2 events/h

(95%CI 4.4, 21.2). The bariatric surgery group also had lower odds of OSA at one year.

However, after adding the change in BMI that occurred with weight loss to this model, there

was no significant difference seen based on the treatment group assigned. This supports the

notion that any reduction in OSA severity associated with bariatric surgery is related to

weight loss and is otherwise independent from the type of surgical procedure.

b) Positional OSA

Two before-and-after studies had reported both supine and non-supine AHI [2, 3], however,

only one study [4] reported the percent of total sleep time spent in the supine position. Given

the lack of certainty regarding the amount of time spent in supine and non-supine sleep

across all studies, we did not feel it was appropriate to perform quantitative analysis.

Weight loss appeared to reduce the non-supine AHI more significantly than supine AHI in

both studies, with no or minimal non-supine OSA evident post-surgery (supine AHI dropped

from 41.5 to 12.2 events/h in Fredheim et al. [2], and from 32.1 to 15.8 events/h in Peromaa-

Haavisto et al. [3]; non-supine AHI dropped from 25.9 to 3.1 events/h in Fredheim et al. [2],

and from 24.4 to 6.3 events/h in Peromaa-Haavisto et al. [3]).

Another study aimed to determine the prevalence of positional OSA in patients undergoing

bariatric surgery [4]. They used the Cartwright’s definition for positional OSA (i.e. supine AHI

≥ 2 times non-supine AHI) [5], however, patients could have spent between 10 – 90% of

sleep in the supine position to be considered in the study. No pre- and post-surgery supine

and non-supine AHIs were available for review. The prevalence of positional OSA after

bariatric surgery in their study cohort was 62.7%. In the final analysis, 35.2% (32/91 patients)

no longer had OSA after surgery.

c) Impact of gender on OSA in participants undergoing bariatric surgery

Only one study examined the influence that gender has on bariatric surgery outcomes [6].

Lettieri et al. reported that men had higher baseline AHIs, experienced larger absolute

reductions (49.5 ± 26.7 events/h vs 14.7 ± 13.5 events/h, p<0.001) as well as higher relative

reductions in AHI compared to women. Furthermore, despite less dramatic reductions in AHI

than men, women had less severe disease at the post-surgery sleep study and were more

likely to be classified in milder OSA categories than men.

Another study that had been identified in our initial search but was not included in the final

meta-analysis (due to suspected overlap with another publication from the same author

group) did explore the effect of gender on obesity indices, metabolic outcomes and sleep

parameters in patients with OSA, obesity and type 2 diabetes mellitus (T2DM) after

laparoscopic RYGB [7]. In 35 participants, there were no significant differences in pre- and

post-surgery AHI or BMI, or the change in AHI and BMI associated with surgery [8]. Overall,

there was very limited evidence examining the impact that gender has on OSA outcomes

following surgery. As such, more data will be required in order to determine the robustness

of the available evidence.

Additional results from the meta-analysis

a) Impact of bariatric surgery on oxygen desaturation index 4% (ODI4%)

In addition to reporting the changes in AHI, four studies also reported pre- and post-surgery

ODI (another marker of OSA severity), however, only three (94 participants) could be meta-

analysed as they used the same oxygen desaturation definition of ≥4% [7, 9, 10]. The WMD

for change in ODI4% was -28.8 events/h (95%CI -46.3, -11.4) with a high I²=95.2%.

b) Individual participant data - subgroup analysis (gender)

We performed sub-group analysis based on gender in the bariatric surgery group (n=39) at

one-year post randomisation [11, 12]. Males were more overweight and had higher pre-

surgery AHI than females, however, there was no significant difference in mean change of

AHI, BMI and weight apart from a slightly higher percent change reduction in AHI in females

(males: -43.9%, females: -56.0%) despite a slightly lower percent change reduction in BMI

(males: -18.9%, females: -17.0%). In this group of participants, more men still had severe

OSA at one-year post randomisation compared with women (53% (10/19) vs 20% (4/20)).

DISCUSSION

CPAP vs bariatric surgery for treatment of OSA

CPAP is the gold standard treatment for OSA. A recent RCT comparing bariatric surgery and

CPAP showed that bariatric surgery may be a reasonable alternative to CPAP [13].

However, there was a large crossover of patients (50%) from the bariatric surgery group to

the CPAP group, suggesting that it may not be an acceptable therapy to all-comers. It was

also interesting to note that the CPAP group lost weight (approximately mean 5kg) over an

18-month period, contrary to a recent meta-analysis of 25 RCTs and 3181 patients [14]

suggesting that OSA treatment with CPAP promotes weight gain of approximately 0.42 kg

over a median of three months. Perhaps the patient group in the study by Bakker et al. were

a more selected group who were “primed” to lose weight, given the potential for

randomisation into a bariatric surgery arm.

The authors also introduced a new parameter called the “Effective AHI”, which takes into

account the number of sleep disordered breathing events both when the patient is asleep

with CPAP and when the patient is asleep but not using CPAP [15]. This parameter is an

example of the application of a tool to measure the effectiveness of OSA treatment. The

effectiveness of OSA treatment is important because it takes into consideration both the

efficacy (i.e. the ability of the treatment to overcome airway collapse) as well as the time

course over which the treatment is being used (i.e. adherence) and gives a better sense of

overall OSA control [16, 17]. Tools to measure the “Effective AHI” as suggested by Bakker et

al. [13] may also be used to facilitate comparison of OSA treatment effectiveness across

OSA treatment modalities as has been demonstrated by other investigators, such as

Sutherland et al. [16]. These sorts of tools could help with deciphering which OSA treatment

would prove to be most beneficial to a particular patient based on the efficacy of the

treatment as well as the patient’s ability to tolerate and comply with the treatment in question

(e.g. CPAP versus mandibular advancement splint [16]).

SUPPLEMENTARY DATA FIGURES

Fig. S1. Pre-surgery compared to post-surgery for the primary outcome of ∆weight (kg) forest plot. SD: standard deviation, CI: confidence interval. Note that these studies are referenced based on the reference list in the main manuscript.

Fig. S2. Bubble plot of weighted mean difference for change in AHI versus follow-up duration (time between surgery and post-surgery sleep study). AHI: apnoea-hypopnoea index (events/h); WMD: weighted mean difference for change in AHI (events/h).

Fig. S3. Bubble plot of weighted mean difference for change in BMI versus follow-up duration (time between surgery and post-surgery sleep study). BMI: body mass index (kg/m²); WMD: weighted mean difference for change in BMI (kg/m²).

Fig. S4. Individual participant data (bariatric surgery group) from two RCTs [11, 12] – Percentage (%) of participants with OSA and distribution of severity of OSA at each time-point [baseline, 1y follow-up and 2nd follow-up (i.e. 2y for Dixon et al. [11] and 3y for Feigel-Guiller et al. [12])]. All participants must have had a baseline and 1y follow-up sleep study to be included in this graph. OSA: obstructive sleep apnoea; RCT: randomised controlled trial.

Fig. S5. Individual participant data (bariatric surgery group) from two RCTs [11, 12] – AHI at baseline, 1y follow-up and second follow-up (i.e. 2y for Dixon et al. [11] in Fig. S5a and 3y for Feigel-Guiller et al. [12] in Fig. S5b)]. All participants must have had a baseline and 1y follow-up sleep study to be included in this graph. AHI: apnoea-hypopnoea index (events/h); OSA: obstructive sleep apnoea; RCT: randomised controlled trial.

Fig. S6. Individual participant data (bariatric surgery group) from two RCTs [11, 12] – Weight (kg) at baseline, 1y follow-up and second follow-up (i.e. 2y for Dixon et al.[11] in Fig. S6a and 3y for Feigel-Guiller et al.[12] in Fig. S6b)]. All participants must have had a baseline and 1y follow-up sleep study to be included in this graph. OSA: obstructive sleep apnoea; RCT: randomised controlled trial.

Fig. S7a. Individual participant data (bariatric surgery group) from two RCTs [11, 12] – AHI and weight at one year. There is no relationship between the amount of weight loss and the improvement in AHI at one year. AHI: apnoea-hypopnoea index (events/h); RCT: randomised controlled trial.

Fig. S7b. Individual participant data (bariatric surgery group) from two RCTs [11, 12] – AHI and BMI at one year. There is no relationship between the reduction in BMI and the improvement in AHI at one year. AHI: apnoea-hypopnoea index (events/h); BMI: body mass index (kg/m²); RCT: randomised controlled trial.

SUPPLEMENTARY DATA TABLES

Table S1

Quality of before-and-after studies using the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group developed by the National Heart, Lung, and Blood Institute [18].

Study General

rating

Study notes

Aguiar et al. 2014 [19] Good

Bae et al. 2014 [20] Fair Possible selection bias. Only 10/67(15%) eligible

participants had post-surgery PSG.

da Silva et al. 2013 [21] Fair Possible selection bias with 18 participants not

contacted; >20% lost to follow-up

Del Genio et al. 2016 [22] Good

de Raaff et al. 2016 [23] Fair >50% lost to follow-up but also had a large

sample size

Dixon et al. 2005 [24] Good Only 27/49(55%) eligible participants agreed to

have the follow-up PSG. Despite this, the authors

did account for the lost to follow-up.

Fritscher et al. 2007 [25] Fair Possible selection bias: 128 bariatric surgeries

performed, only 20 participants had a PSG prior

surgery to investigate for subjective daytime

somnolence symptoms. Subsequently, 18 had

OSAS, hence were recruited into the study.

Guardiano et al. 2003 [26] Fair >50% lost to follow-up. Small sample size (28

offered but only eight had follow-up PSG)

Haines et al. 2007 [27] Good Despite >20% lost to follow-up, authors did

account for drop out (101/179 participants had

post-surgery PSG). There was also a relatively

larger sample size of patients for review.

Krieger et al. 2012 [28] Good Individual participant data provided by author.

Lettieri et al. 2008 [6] Good

Morong et al. 2014 [4] Good

Pallayova et al. 2011 [29] Good

Peromaa-Haavisto et al.

2017 [3]

Good Type 3 PG used.

Priyadarshini et al. 2017

[30]

Good

Rao et al. 2009 [31] Fair Possible selection bias. Patients with OSA were

randomly offered post-surgery PSG.

Ravesloot et al. 2014 [32] Good Despite >36% lost to follow-up, they were

accounted for. There was reasonable sample

size (171 participants pre-surgery had OSA on

PSG, 110 patients had 1st post-surgery PSG, 50

participants had 2nd post-surgery PSG).

Shaarawy et al. 2016 [9] Fair Small sample size (n=22) and no statistical

power was given.

Suliman et al. 2016 [33] Fair 36% were lost to follow-up and small sample size

(n=20).

Valencia-Flores et al.

2004 [10]

Fair Possible selection bias. 29/65(45%) referred

participants accepted 2nd invitation for

follow-up/post-surgery PSG. No particular sample

size given.

Xie et al. 2016 [34] Poor Small sample size had repeat PSG, and follow-

up PSG was offered at random. Only 15 of 167

participants had both pre- and post-surgery PSG.

Zou et al. 2015 [7] Good Well-designed study hence rated “Good”.

Potential selection bias as participants included

had to have both obesity and Type 2 Diabetes

Mellitus.

1st: first; 2nd: second; PG: polygraphy; PSG: polysomnography; OSAS: obstructive sleep

apnoea syndrome.

Table S2

Quality of non-randomised controlled trials using the Cochrane’s Risk of Bias in Non-

Randomised Controlled Trials (ROBINS-I) assessment tool [35].

Bakker et al. 2014 [1] Fredheim et al. 2013 [2]

Domain 1

Bias due to confounding

Moderate

- Participants chose

their own intervention

Moderate

- Participants chose

their own intervention

Domain 2

Bias in selection of

participants into the study

Low

- Intervention decided

by both participant

and clinician prior to

proceeding with study

Low

- Intervention decided

by both participant

and clinician prior to

proceeding with study

Domain 3

Bias in classification of

interventions

Low

- Interventions were

clearly defined

Moderate

- Possibility that

participants may be

more likely to engage

in intervention (eg.

surgical arm) as

working towards a

goal

Domain 4

Bias due to deviations from

intended interventions

Low Low

- Minimal cross over

Domain 5

Bias due to missing data

Low

- All participant

outcomes were

available

Low

- All participant

outcomes were

available

Domain 6

Bias in measurement of

outcomes

Moderate

- Not mentioned if

sleep scoring

technician was

blinded to the

intervention arm

- Participant

choice/decision may

influence some of the

outcomes measured

Moderate

- Sleep study

recordings were

scored manually by

the same person,

however, this was not

blinded (study

authors scored the

sleep studies when

this was inquired with

the author)

- Outcome assessors

were blinded to the

intervention

Domain 7

Bias in selection of the

reported result

Low

- No multiple outcome

measurements were

made

Moderate

- Skewed data was

performed and log

regression was

conducted to take

into account for

certain factors

Overall Risk of Bias Moderate

- Unpredictable

Moderate

- Unpredictable

Table S3

Quality of randomised controlled trials using the Cochrane Risk of Bias (ROBINS2)

assessment tool [35]. Outcome: Apnoea-hypopnoea index (events/h)

Studies/Domains Dixon et al. 2012

[11]

Feigel-Guiller et al.

2015 [12]

Bakker et al. 2017

[13]

Randomisation

process

Low Low Low

Deviations from

intended

Low Some concerns Some concerns

Missing outcome

data

Low Low Low

Measurement of the

outcome

Low Some concerns Some concerns

Selection of the

reported results

Some concerns Low Low

Overall bias Low Some concerns Some concerns

Table S4

GRADE worksheet

(assessing the

quality of evidence

across studies for an

outcome) of

included studies in

systematic review

and meta-analysis.

[36] Quality criteria

Rating Footnotes Quality

of the

evidence

Primary outcomes (AHI and BMI)

Risk of bias Very

serious

(-2)

Majority are before-and-after studies, variable

inclusion criteria/study design, high drop-out

rate & uncertain on outcome in drop-out

group. For CPAP vs BS study, large cross-

over group.

Inconsistency No All studies had relevant populations,

interventions, comparators and outcomes,

and similar treatment effect whereby all

patients did have weight loss and

improvement in AHI. However, there were

also variable follow-up time points (eg

3mo,6mo, 12mo, 5 y) and at least moderate

heterogeneity despite accounting for time.

Indirectness No All studies did perform a before-and-after

surgery review, which should be able to

address the outcome in question.

Imprecision No Confidence intervals overall did not cross

zero and the results were consistent across

all studies. There were variable sample sizes

(n=8 to 205). We are certain that the

intervention has beneficial outcomes. Very low

Publication Bias Unlikely Funnel plots in general looked symmetrical.

Not confirmed but not enough evidence to

downgrade in this case.

Large effect Large (+1) All studies (large and small) did demonstrate

a significant change in AHI and BMI despite

study design.

Dose-response

gradient

No Not applicable

Plausible

confounding would

change the effect

No Not applicable

AHI: apnoea-hypopnoea index (events/h); BMI: body mass index (kg/m2); BS: bariatric

surgery; CPAP: continuous positive airway pressure.

Table S5

Publication bias statistics – Begg’s and Egger’s test results.

Parameter Begg’s test (p-value) Egger’s test (p-value & 95%CI)

WMD (Change in AHI) 0.166 0.234 (-0.257, 0.068)WMD (Change in BMI) 0.113 0.062 (-0.599, 0.017)WMD (Change in weight) 0.304 0.036 (0.008, 0.189)

AHI: apnoea-hypopnoea index (events/h); BMI: body mass index (kg/m²); CI: confidence interval.

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