Bariatric surgery or Non-Surgical Weight Loss for Obstructive Sleep Apnea? A systematic review and comparison of meta-analyses

Running Title: Bariatric Surgery and OSA

Hutan Ashrafian* PhD MRCS, Tania Toma, Simon P. Rowland BSc(Hons.) MBBS,

Leanne Harling BSc(Hons.) MBBS MRCS, Alan Tan BA MB BChir, Evangelos

Efthimiou MD FRCS, Ara Darzi KBE FMedSci, Thanos Athanasiou MD PhD FRCS

FETCS

Department of Surgery and Cancer, Imperial College London

*Corresponding author: Hutan Ashrafian, The Department of Surgery and Cancer,

Imperial College London. 10th Floor, Queen Elizabeth the Queen Mother (QEQM)

Building, Imperial College Healthcare NHS Trust at St Mary’s Hospital, Praed Street,

London, W2 1NY, United Kingdom. E-mail: h.ashrafian@imperial.ac.uk. Telephone:

+44 (0)20 7886 7651, Fax: +44 (0)20 7886 6309.

Manuscript type: Systematic Review

Financial disclosure: None

Conflict of Interest: The authors declare that they have no conflict of interest.

Word Count: 2983

Number of figures: 3

Number of tables: 3

Supplementary appendix: 1

Number of References: 90

Abstract

Background: Obstructive sleep apnea (OSA) is a well-recognized complication of obesity.

Non-surgical weight loss (medical, behavioral and lifestyle interventions) may improve OSA

outcomes, although long-term weight control remains challenging. Bariatric surgery offers a

successful strategy for long-term weight loss and symptom resolution.

Objectives: To comparatively appraise bariatric surgery vs. non-surgical weight loss

interventions in OSA treatment utilizing body mass index (BMI) and apnea hypopnea index

(AHI) as objective measures of weight loss and apnea severity.

Methods: A systematic literature review revealed 19 surgical (n=525) and 20 non-surgical

(n=825) studies reporting the primary endpoints of BMI and AHI before and after intervention.

Data were meta-analysed using random effects modeling. Subgroup analysis, quality scoring

and risk of bias were assessed.

Results: Surgical patients had a mean pre-intervention BMI of 51.3 and achieved a significant

14kg/m2 weighted decrease in BMI (95%CI [11.91,16.44]), with a 29/h weighted decrease in

AHI (95%CI [22.41,36.74]). Non-surgical patients had a mean pre-intervention BMI of 38.3

and achieved a significant weighted decrease in BMI of 3.1kg/m2 (95%CI [2.42,3.79]), with a

weighted decrease in AHI of 11/h (95%CI [7.81,14.98]). Heterogeneity was high across all

outcomes.

Conclusions: Both bariatric surgery and non-surgical weight loss may have significant

beneficial effects on OSA through BMI and AHI reduction. However, bariatric surgery may

offer markedly greater improvement in BMI and AHI than non-surgical alternatives. Future

studies must address the lack of randomized controlled and comparative trials in order to

confirm the exact relationship between metabolic surgery and non-surgical weight loss

interventions in OSA resolution.

Abstract Word Count: 249

Key words: ‘obstructive sleep apnea’; ‘body mass index’; ‘intervention’; ‘surgery’; ‘weight

loss’; ‘apnea-hypopnea index’

Introduction

The global prevalence of obesity is increasing with the World Health Organization estimating

11% of adults are obese worldwide[1]. Alongside this increase in obesity is a continuous rise in

the incidence of obstructive sleep apnea (OSA), which is now thought to affect at least 100

million adults[2]. OSA is characterized by repeated periods of complete or partial upper airway

collapse during sleep, resulting in episodes of apnea and hypopnea. Severe OSA is indicated by

polysomnographic measurement of over 30 obstructive apnea and hypopnea episodes per hour of

sleep (an apnea-hypopnea index (AHI) of >30)[3]. In such severe cases, OSA may be

complicated by hypertension, cardiovascular disease, stroke and excessive daytime sleepiness, as

well as a diminished quality of life, decreased cognitive function and elevated risk of motor

vehicle accidents[4]. Obesity accounts for up to 58% of adult OSA cases[5], with evidence from

the Wisconsin Sleep Cohort Study suggesting that relative to stable weight, individuals with a

10% increase in body weight have a 6-fold elevated risk of developing moderate-to-severe OSA.

Continuous positive airway pressure (CPAP) is an established symptomatic therapy for OSA,

however it may cause skin irritation, airway dryness, claustrophobia and general discomfort

leading to reduced patient compliance[6]. As a result, lifestyle weight loss interventions such as

exercise promotion, dietary modification, pharmacotherapy and behavioral therapy are therefore

increasingly recommended as alternatives or adjuncts to CPAP[7, 8] within the context of

established OSA treatments (such as otolaryngologic surgery that addresses the tonsils, base of

tongue, epiglottis and pharynx). However, although these weight loss therapies may improve

both OSA outcomes and the metabolic sequela of obesity, long-term weight control and

consequently OSA resolution remains challenging.

Bariatric surgery offers an alternative method of maintaining long-term weight reduction and

improving OSA outcomes whilst at the same time improving glycaemic control and reducing

cardiovascular and cancer risk[9]. Indeed, a recent systematic review demonstrated that over 75%

of patients receiving bariatric surgery demonstrated some improvement in OSA outcomes[10].

However, although there is evidence to suggest both bariatric surgical and non-surgical

interventions may improve OSA outcomes through weight reduction, there is a paucity of studies

directly comparing these treatment strategies. This study therefore aims to systematically review

and meta-analyze the current evidence to concurrently appraise bariatric surgery and non-surgical

weight loss interventions in the treatment of OSA, through the assessment of AHI and BMI as

summary outcome parameters.

Methods

Literature Search

A literature search was performed using PubMed, Ovid, Embase, and Cochrane databases using

combinations of the terms “sleep apnea”, “obstructive sleep apnea”, and “weight loss”, “weight

reduction”, “bariatric surgery”. The ‘related articles’ function in PubMed was used as a further

check of rigor. The last date for this search was 25th July 2013. The search strategy is outlined in

Figure 1. All studies have been listed in Table 1 (bariatric surgery) and Table 2 (non-surgical

weight loss management) to offer an overview of the appraised literature in addition to

identifying the proportion that offer both outcomes of BMI and AHI.

Inclusion and Exclusion Criteria

All studies reporting Body Mass Index (BMI) and Apnea-Hypopnea Index (AHI) before and after

either (a) bariatric surgery; or (b) non-surgical weight loss intervention, were included. Studies

were excluded from the review if: (1) Inconsistency of data did not allow valid extraction; (2)

Studies did not report both AHI and BMI (3) they reported sleep study and other

polysolomongraphic measures that did not include AHI (e.g. RDI (respiratory disturbance index)

which is similar but not interchangeable with AHI) (3) Data was duplicated; (4) The trial was

carried out on animal models; (5) English language full text was not available.

Based on these criteria, two assessors (HA and SR) independently selected studies for further

examination by title and abstract review. All potentially eligible studies were retrieved in full for

further evaluation. Any disagreement was resolved by discussion with the senior author.

Data Analysis

Two authors (HA and SR) independently extracted the following data from each paper using a

standardised spreadsheet: First author; year of publication; study type; number of subjects and

study population demographics. Specific outcome data was retrieved for the following: (i)

Apnoea Hypopnoea Index (AHI) (ii) Body Mass Index (BMI).

Meta-analysis was performed in line with recommendations from the Cochrane Collaboration

and in accordance with both PRISMA (Preferred Reporting Items for Systematic Reviews and

Meta-Analyses) and MOOSE (Meta-analysis Of Observational Studies in Epidemiology)

guidelines.[11, 12] Analysis was conducted by use of Review Manager® Version 5.3.4 for

Windows (The Cochrane Collaboration, Software Update, Oxford, UK) and STATA v.12

statistical analysis software.

Data was analyzed using a random effects model. Continuous data were investigated using

weighted mean difference (WMD) as the summary statistic, reported with 95% confidence

intervals (CI). The point estimate of the WMD was considered statistically significant at p < 0.05,

if the 95% confidence interval did not include the value zero. Categorical variables were

analyzed using the odds ratio (OR). An OR of <1 favored the treatment group and the point

estimate of the OR is considered statistically significant at the p<0.05 level, if the 95% CI does

not include the value 1.

Heterogeneity

Inter-study heterogeneity was explored using the Chi2-statistic, but I2 was calculated to quantify

the degree of heterogeneity across trials that could not be attributable to chance alone. When I 2

was >50%, significant statistical heterogeneity was considered to be present.

Three strategies were used to assess data validity and heterogeneity: (1) Sensitivity analysis of

higher quality studies (Quality score >7); (2) Funnel plots to evaluate publication bias; (3)

Assessment of publication bias using Egger’s test for small-study effects.

Quality Scoring

Quality assessment of each study was performed by attributing a quality assessment score using a

modification of the Newcastle-Ottawa scale[11]. Studies attaining greater than the median score

of 7 (out of a maximum 15) were defined to have ‘higher matching quality’ and were included in

subgroup analysis. Modified Newcastle-Ottawa scoring criteria are shown in the Supplementary

Appendix: Table 1 and Table 2.

Results

(a) Surgical Group: Nineteen studies[13-26] fulfilled the inclusion criteria, producing a pooled

data set of 525 patients with obstructive sleep apnea (OSA) undergoing bariatric surgery (Table 1

– listing bariatric surgical studies on OSA outcomes). Fifteen of these were non-randomized,

prospective observational studies,[13-23]; three were retrospective cohort studies[24, 25], and

one was a prospective randomized controlled trial [26]. One study[23] compared the effect of two

surgical modalities on OSA. Each of these groups was considered independently in the following

analysis.

(a) Non-Surgical Group: Twenty studies[17, 21, 26-40] fulfilled the inclusion criteria,

producing a pooled data set of 825 patients with obstructive sleep apnea (OSA) undergoing non-

surgical therapies (Table 2 – listing non-surgical studies on OSA outcomes). Thirteen were

non-randomized, prospective observational studies,[17, 21, 28-37, 41] and 7 were randomized

controlled trials (RCT),[26, 27, 38, 39] of which one was multicenter[38]. Two studies[38]

compared the effect of two non-surgical modalities on OSA. Each of these groups was

considered independently in the following analysis.

Primary Outcomes

Apnea Hypopnea Index (AHI):

(a) Surgical Group: Surgical intervention was associated with a significant post-operative

reduction in AHI (WMD 29.57, 95%CI [22.41, 36.74], p<0.00001), however, this was associated

with significant inter-study heterogeneity (Chi2 1121.15, p<0.00001, I2 98%) (Figure 2a).

(b) Non-Surgical Group: Non-surgical weight loss intervention was associated with a significant

post-operative reduction in AHI (WMD 11.39, 95%CI [7.81, 14.98], p<0.00001), again with

significant inter-study heterogeneity (Chi2 117.20, p<0.00001, I2 82%) (Figure 2b).

Body Mass Index:

(a) Surgical Group: Surgical intervention was associated with a significant post-operative

reduction in BMI (WMD 14.18, 95%CI [11.91, 16.44], p<0.00001), however, this was again

associated with significant inter-study heterogeneity (Chi2 562.80, p<0.00001, I2 97%) (Figure

3a).

(b) Non-Surgical Group: Non-surgical weight loss intervention was associated with a significant

post-operative reduction in BMI (WMD 3.10, 95%CI [2.42, 3.79], p<0.00001), again with

significant inter-study heterogeneity (Chi2 46.70, p=0.001, I2 55%) (Figure 3b).

Quality Scoring and Sensitivity Analysis

The overall quality of studies is outlined in the supplementary appendix: Table 2. Subgroup

results may be compared with results from the overall analysis in Table 3.

(a) Surgical Group: Of the 19 studies included in the surgical group, 3 were considered to be of

high quality,[17, 23, 26] scoring above or equal to the median of 7. One study[23] compared the

effect of two surgical modalities on OSA and, as with the overall analysis, each of these groups

was considered independently.

Analysis of high quality studies again demonstrated a reduction in both AHI (WMD 26.00,

95%CI [17.27, 34.74], p<0.00001) and BMI (WMD 13.49, 95%CI [10.20, 16.79], p<0.00001)

after surgery, without significant heterogeneity (BMI: Chi2 6.56, p=0.09, I2 54%; AHI: Chi2 3.82,

p=0.28, I2 21%).

(b) Non-Surgical Group: Of the 20 studies included in the non-surgical group, 10 were of high

quality,[17, 26-29, 38, 39, 41] scoring ≥7. Again, one study[38] compared the effect of two non-

surgical modalities on OSA and these groups were considered independently.

Analysis of high quality studies similarly demonstrated a reduction in both AHI (WMD 6.21,

95%CI [2.68, 9.75], p=0.0006) and BMI (WMD 2.92, 95%CI [1.82, 4.02], p<0.00001) after

surgery, although significant heterogeneity remained for both outcomes (BMI: Chi2 31.84,

p=0.0004, I2 69%; AHI: Chi2 52.16, p<0.00001, I2 81%).

Heterogeneity Assessment: Bias Exploration

Funnel plots were used to assess for publication bias (supplementary appendix: Figure 1).

Visual inspection revealed no funnel plot asymmetry and Egger’s test revealed no significant

small study effects (supplementary appendix: Table 3) for either AHI or BMI outcomes.

Discussion

In 525 subjects with a mean pre-intervention BMI of 51.3, bariatric surgery offered a weighted

decrease of BMI by 14kg/m2 and a weighted decrease of AHI by 29/h. Studies of patients

undergoing non-surgical weight loss therapy revealed 825 subjects with a pre-intervention mean

BMI of 38.3. Non-surgical weight loss intervention was associated with a weighted decrease in

BMI by 3.1kg/m2 and a weighted decrease of AHI by 11/h.

This study offers the first available means to objectively compare the effects of surgical and non-

surgical weight loss strategies on BMI and sleep apnea severity (measured through AHI).

Although due to the lack of comparative trial data bariatric and non-surgical patients differed in

their baseline characteristics, both the weight loss effects of surgery (BMI reduction) and

improvements in OSA severity (AHI reduction) were found to be greater in surgical studies

(Table 2 vs. Table 3). Although cursory review may suggest that for each unit of BMI decrease,

non-surgical treatment may offer more efficient changes in AHI score, the lack of direct

comparative trials precludes this conclusion from this analysis. However, the analysis of high

quality studies significantly reduced inter-study heterogeneity and also revealed similar results

favoring a robustly stronger decrease in both AHI and BMI with bariatric surgery when

compared to non-surgical weight loss strategies.

Bariatric surgery is now considered the most efficacious treatment for morbid obesity, reflected

by over 340,000 metabolic operations performed annually[42]. The mechanisms through which

these procedures may alleviate OSA have been previously summarized in the BRAVE effects,

consisting of bile flow alteration, reduction of gastric size, anatomical gut rearrangement, vagal

manipulation and enteric gut hormone modulation in addition to a post-operative modulation of

eating behavior and possibly improved lifestyle and exercise activity [43]. Whilst these effects

likely contribute to OSA improvement through a myriad of downstream targeted metabolic

effectors that act as drivers of weight loss, their actions on systemic metabolism (including those

on insulin resistance and diabetes) may also reduce OSA burden through the metabolic drivers of

OSA aetiology. Furthermore, surgically induced weight loss can also relieve excess pressure on

the neck, diaphragm and upper airways, restoring functional residual capacity and resolving the

alterations in upper airway structure that predispose airway collapse[5, 44].

There is accumulating evidence that OSA results as a manifestation of metabolic syndrome.

Indeed, when adjusted for age, BMI, smoking and alcohol consumption, OSA has been

independently associated with increased systolic and diastolic blood pressure, higher fasting

insulin and abnormal lipid profiles[45]. Emerging data also suggests a correlation between type-2

diabetes and OSA. In a sample of 595 males with suspected OSA, type-2 diabetes was evident in

30.1% OSA patients, but only in 13.9% of non-apnoeic snorers[46]. This causation can be

explained by a variety of possible mechanisms including elevated sympathetic nervous system

activity and impaired glucose metabolism secondary to hypoxia. Furthermore, the chronic sleep

debt resulting from OSA itself may be independently associated with perturbed glucocorticoid

regulation and glucose tolerance[47].

OSA also appears to be accompanied by the release of pro-inflammatory adipokines. Patients

with OSA demonstrate elevated plasma levels of interleukin (IL)-6 and tumor necrosis factor-

alpha (TNF-α), as well as the inflammatory biomarker C-reactive protein (CRP) [48, 49].

Bariatric/metabolic surgery may significantly reduce the concentration of both IL-6 and CRP[49],

as well as improving insulin resistance[50]. However, despite the restoration of inflammatory

cytokine levels after surgical weight loss, the underlying mechanisms of this inflammatory

cascade and its relation to OSA still remain elusive[51].

An independent association between adipokines and OSA has also recently been established.

Obese individuals demonstrate insensitivity to the adipocyte-derived hormone leptin, which is

produced at chronically high levels. Furthermore, patients with OSA also display significantly

higher levels of leptin when compared to non-OSA controls[52]. Bariatric surgery has been

shown to significantly reduce serum leptin, independent to BMI (8.1±7.3 to 6.1±5.5 ng/ml,

p<0.001)[53], giving rise to a potential weight-independent mechanism for OSA resolution

through modification of the regulatory mechanisms that control appetite and energy expenditure

via the hypothalamic-pituitary axis.

However, despite its apparent benefits, concerns about the safety of bariatric surgery still exist,

especially in the early post-operative period. Indeed, surgical complication rates, morbidity and

mortality may all be increased by factors such as increasing BMI and coexisting medical

conditions such as OSA[54]. Nevertheless, 30-day outcomes from a recent large observational

study (n=4776) revealed a surgical mortality rate of only 0.3%, with only 4.3% experiencing an

adverse outcome[55]. As such, the risks of bariatric surgery should be carefully weighed up

against the long-term risk of severe obesity when considering the most appropriate treatment

modality in these often complex patients.

Non-surgical weight loss methods also improved OSA outcomes, despite having more modest

results than surgical approaches. Such strategies predominantly aimed to encourage lifestyle

modifications through exercise, dietary interventions, or a combination of both. Less common

interventions included pharmacotherapy and behavioral counseling. The effects of these therapies

have been hypothesized to range beyond simple weight reduction, with exercise acting to

beneficially improve AHI through enhancement of thermogenic control, improvement in upper

airway muscle tonus and the restoration of chemoreceptor sensitivity to hypoxia[7, 56]. However,

previous meta-analysis suggests that non-surgical interventions vary in effectiveness, with dietary

interventions exhibiting a greater beneficial effect on both AHI and BMI than exercise alone[7].

Furthermore, although promising in the short-term, the long-term durability of therapies such as

intensive dietary modification remains questionable.

Strengths and Limitations

This meta-analysis statistically appraises pooled data collected from 525 patients in 19 surgical

studies and 825 patients receiving non-surgical interventions in 20 studies. However, the results

presented here should be considered in the context of a number of limitations. Firstly, many of

the trials included are inherently limited by their study design with only one surgical study and

three non-surgical studies being randomized controlled trials. The majority of remaining trials

were prospective observational studies, with three studies reporting data retrospectively.

Secondly, significant statistical heterogeneity was evident in our results, attributable to a variety

of possible confounding factors. Aside from the aforementioned differences in study design, trials

in both arms varied in follow-up and differed in patient demographics. There was also great

variation in the year of publication, ranging from 1988 to 2014. As such, our analysis may not

reflect the difference between current and older weight loss therapies, or the evolution in

techniques of assessing AHI. Inconsistencies also arise in the type of intervention delivered to

both surgical and non-surgical arms. Non-surgical interventions encompassed an assortment of

dietary, exercise, drug or behavior-related therapies, varying in a range of factors such as

intensity, frequency of use and the adjunct use of CPAP. Similarly, surgical studies exhibited

variation in follow-up, type of procedure, and showed discrepancies in the surgical outcome

measures assessed. Furthermore, when comparing the two meta-analytical groups the mean

starting BMI as well as sleep apnea severity appears to be much higher in the surgical group,

which may effect the overall reduction in BMI as well as degree of decrease in AHI. Other

sources of bias influencing our analysis of surgical studies include ascertainment bias, treatment

bias, intervention bias, differential bias and bias due to measuring BMI as a summary outcome.

Thirdly, despite offering clarification into the comparison of surgical and non-surgical studies by

pooling results from both intervention types, our analysis still does not statistically quantify the

difference in effect between them. Fourth, due to our selection criteria including the reporting of

both BMI and AHI pre and post intervention, many well-conducted studies were eliminated from

our study due to incomplete data (Table 1 and Table 2). Therefore our analysis is limited by the

pool of patients included and might not be entirely representative of all interventions in the

current literature.

Finally, we note a possible limitation in the use of AHI as the summary parameter for OSA

treatment outcomes. AHI, derived from overnight polysonography tests, is accepted as the ‘gold

standard’ measure in OSA diagnostics; however, there are uncertainties in the validity and

reliability of its use. AHI is derived from the number of apneas and hypopneas that occur during

a given sleep cycle, however, there appears to be a lack of standardization across laboratories and

studies in defining what criteria constitutes an apneic or hypopneic event. As a result of the

varying methods of measuring AHI, discrepancies in the magnitude of AHI and therefore

prevalence of OSA may exist amongst included studies[57]. Furthermore, the threshold for

defining abnormal AHI was previously set at above 5 events/hour, and as such there may be

difficulties comparing OSA severity in older studies with the more current literature [58].

Finally, within non-surgical studies Eggers test revealed a significant small study effect when

assessing pre and post intervention BMI. A possible explanation for this is the inclusion of small

samples of patients in interventions of earlier surgical studies. Furthermore, small study effects

may limit the analysis through lack of power, publication bias, ascertainment bias and design

bias.

Conclusion

In summary, we demonstrate that both bariatric surgery and non-surgical interventions may

alleviate the burden of OSA through the reduction of BMI and AHI. However, our analysis

indicates that bariatric surgery offers a markedly greater improvement in BMI and AHI, as well

as the abatement of symptoms that accompany OSA. Bariatric surgery improves airway control

and polysomnographic outcomes via a number of putative mechanisms. These include

modification of cytokine and adipokine profiles, in addition to improved insulin resistance,

altered gut hormone release and eating behaviour. Consequently, bariatric surgery can ameliorate,

if not completely resolve, a number of the metabolic dysfunctions accompanying OSA including

hypertension, hyperglycaemia and dyslipidemia. However, our current research is limited by a

lack of randomized controlled trials and comparative studies between surgical and non-surgical

interventions. Significant inter-study heterogeneity across published trials also limits out ability

to conclusively determine the advantages of surgical treatment over alternative therapies. Future

studies must now address the lack of randomized controlled and comparative trials that should

consider post-intervention periods, response curves and the underlying mechanisms to confirm

the exact relationship between metabolic surgery and non-surgical weight loss interventions in

OSA resolution.

Ethical Approval: For this type of study formal consent is not required

Conflict of interest: The authors declare that they have no conflict of interest

Table 1: Metabolic surgical studies reporting on weight loss and indices of sleep apnea before and after surgery. * = studies reporting the post-operative changes of both Body Mass Index (BMI) and Apnea-Hypopnea Index (AHI) which were subsequently included in the analysis to derive the weighted mean change of BMI and AHI. RYGB = Roux-en-Y Gastric Bypass, VBG = Vertical Banded Gastroplasty, HG = Horizontal Gastroplasty, BPD = Biliopancreatic diversion, DS = Duodenal Switch, SG = Sleeve Gastrectomy, CPAP = continuous positive airway pressure. NS= Not Specified

Author Metabolic Operation Subject Number

Follow Up

(months)

Body Mass Index(kg/m2)

Apnea-Hypopnea Index(per hour)

Pre-op Post-op Pre-op Post-op

Harman 1982[59] Jejuno-ileal Bypass 4 24 NS NS 78 1.4

Peiser 1984[60] RYGB 15 2-4 NS NS 81.9 15.0Peiser 1984[60] RYGB 6 4-8 NS NS 81.9 5.5Charuzi 1985[61] RYGB 13 6 NS NS 88.8 8.0Charuzi 1987[62] RYGB, VBG 46 6 NS NS 58.8 36.1

Rubinstein 1988[34] VBG or diet (unknown split) 12 NS 41 32 57 14

Summers 1990[63] VBG 1 4 54 37 40 <5*Rajala 1991[21] VBG 3 NS 52.2 34.23 44.67 5.33Charuzi 1992[64] RYGB, VBG 47 10.65 NS NS 60.8 8.0Charuzi 1992[64] RYGB, VBG 6 12 NS NS 60.3 12.4Charuzi 1992[64] RYGB, VBG 6 84 NS NS 60.3 34.5

*Sugerman1992[24] RYGB, VBG, HG 40 54 58 39 64 26

Pillar 1994[19] RYGB, VBG 14 4.5 45 33 40 11*Pillar 1994[19] RYGB, VBG 14 90 45 35 40 24

Noseda 1996[65] VBG + CPAP Diet + CPAP

39 (VBG=3, Diet=36)

12 NS NS 66.5 50.3

Scheuller 2001[66] BPD, VBG 15 12-144 NS NS 96.9 11.3*Rasheid 2003[22] RYGB 11 3-21 62 40 56 23*Guardiano 2003[25] RYGB 8 28 49 34 55 14*Valencia-Flores 2004[23] RYGB, VBG 29 13.7 56.5 39.2 53.7 13.7

*Busetto 2005[13] IntraGastric Balloon 17 6 55.8 48.6 59.3 14

*Dixon 2005[14] Gastric Banding 25 17.7 52.7 37.2 61.6 13.4

Lankford 2005[67] RYGB 15 12 48 32 40 (CPAP-11cmH20) NA (CPAP-9cmH20)

Kalra 2005[68] RYGB 10 5.1 60.8 41.6 9.1(median) 0.65(median)

*Poitou 2006[20] RYGB, Gastric Banding 35 12 51.3 39.9 24.5 9.7

*Haines 2007[15] RYGB 101 6-42 56 38 51 15

Grunstein 2007[69] (SOS Study)

RYGB, VBG, Gastric Banding 1592 24 42.2 32.5

24 (Frequency

Apneas)8.3 (Frequency Apneas)

Fritscher 2007[70] RYGB 12 24.2 55.5 34.146.5median (range 33-

140)

16.0median (range 0.9-87

*Martí-Valeri 2007[71] RYGB 30 12 56.53 32.12 63.59 17.45Valera 2007[72] RYGB 56 12 49 NS 35 NS

Kuzniar 2008[73] NS 1 7 44.5 29.4 44 (CPAP-16cmH20) NS (CPAP-8cmH20)

*Lettieri 2008[16] Gastric Banding 24 12 51 32.1 47.9 24.5

Rao 2009[74] Gastric Banding 46 12.6±20 45.2 30 38.11 13.18

*Pallayova 2011[18] RYGB, SG, BPD-DS 23 12 52.3 35.7 45.6 10.1

*Dixon 2012 [26] Gastric Banding 30 24 46.3 36.6 65 39.5

*Fredheim 2013 [17] RYGB 44 12 47.5 33.5 29.3 7.7

*Krieger 2012 Gastric Banding 24 12 47.18 35.62 34.2 19

*Farah 2013 NS 19 7 49 40 41 12.4

*Da Silva 2013 RYGB, sleeve gastrectomy 17 3 46.2 36.6 19 7

*Ravesloot 2014

Gastric banding, RYGB, sleeve gastrectomy 50 17 45 35 49.1 17.4

*Bakker 2014 RYGB, Gastric Banding 12 12 46.7 29.9 35.5 8.9

Weighted Mean (Random Effects) Post-operative Change ↓14.18 ↓29.57

Table 2. Weight loss (non-surgical) studies reporting on weight loss and indices of sleep apnea before and after weight loss intervention. * = studies reporting the post-intervention changes of both Body Mass Index (BMI) and Apnea-Hypopnea Index (AHI) which were subsequently included in the analysis to derive the weighted mean change of BMI and AHI. CPAP = continuous positive airway pressure. NS= Not Specified

Author Lifestyle Intervention

Subject Number

Follow Up

(months)

Body Mass Index(kg/m2)

Apnea-Hypopnea Index

(per hour)Pre- Post- Pre- Post-

Smith 1985[75] Weight loss Advice 15 5.3 NS NS 55 29.2

*Rubinstein 1988[34] Diet or Surgery12 (study proportion unknown)

NA 41 32 57 14

*Pasquali 1990[32] Diet 23 3-14 37.5 30.9 66.5 33

*Rajala 1991[21] Diet 8 NS 50.7 44.1 45.75 31.63

*Schwartz 1991[41] Diet 13 NS 42.0 34.7 83.3 32.5

*Suratt 1987[36] & 1992[37] Diet 8 1month-<24 54 46 90 62

Kiselak 1993[76] Diet 14 4.5-5 54.88 NS 17.63 1.03

Nahmias 1993[77] Diet 24 5-19 NS NS 56.5 17.5

Noseda 1996[65] Diet + CPAP or Surgery + CPAP

39 (Diet=36, Surgery=3) 12 NS NS 66.5 50.3

*Kansanen 1998[30] Diet 15 3 38.1 35.1 29 18

Sampol 1998[35] Diet 67 NS 31.5 25.9 52.3 44.2

Sampol 1998[35](Cured Patients) Diet + exercise 24 11.5 32.8 27.2 44.3 3

*Sampol 1998[35](Cured Patients) Diet + exercise 24 94.3 32.8 30.8 44.3 26.4

Martinez 2005[78] Sibutramine 10 1 25-35Kg/m2 NS 28 27

*Yee 2007[40] Sibutramine and Diet 87 6 34.2 31.0 46 29.6

Verhulst 2009[79] (teenagers) Diet 21 5 NS NS 3.8 1.9

*Barnes 2009[28] Diet + Exercise 10 4 36.1 30.1 24.6 18.3

*Phillips 2009[33] Sibutramine and Diet and Exercise 93 6 34.1 31.6 45.9 30.2

*Johansson 2009[39] Diet 30 2.25 34.4 28.7 37 12

*Ferland 2009[29] Sibutramine and Diet and Exercise 22 12 36.8 35.0 39.8 37.0

*Foster 2009[38] Weight loss Advice 139 12 36.5 36.3 23.5 27.7

*Foster 2009[38] Diet and Exercise 125 12 36.8 33.0 22.9 17.5

*Nerfeldt 2010[31] Diet and behavioral support 23 24 40.0 35.0 43.0 28.0

*Tuomilehto 2010[27] Diet 35 24 33.4 30.9 10 5.4

*Dixon 2012 [26] Diet 30 24 43.8 42.3 57.2 43.2

*Fredheim 2013 [17] Diet 40 12 43.9 39.7 21.8 13.0

*Sengul 2011 Exercise 10 3 29.79 29.2 15.19 11.01

*Pahkala 2014 Diet and Exercise 19 12 33 29.4 10 6

*Papandreou 2012 Diet 20 6 37.99 35.53 58.65 46.78

*Papandreou 2012 Diet 20 6 35.26 32.03 52.4 36.85

Weighted Mean (Random Effects) Post-intervention change ↓3.10 ↓11.39

Table 3- Subgroup Analysis

Outcome SubgroupN Overall effect Heterogeneity

Studies Pre Post WMD 95% CI p Chi2 p I2

(a) Surgical

AHI Overall 19 525 525 29.57 [22.41, 36.74] <0.00001 1121.15 <0.00001 98

Quality Score >7 3 102 102 26.00 [17.27, 34.74] <0.00001 3.82 0.28 21

BMI Overall 19 525 525 14.18 [11.91, 16.44] <0.00001 562.80 <0.00001 97

Quality Score >7 3 102 102 13.49 [10.20, 16.79] <0.00001 6.56 0.09 54

(b) Non-Surgical

AHI Overall 20 825 825 11.39 [7.81, 14.98] <0.00001 117.20 <0.00001 82

Quality Score >7 10 492 492 6.21 [2.68, 9.75] 0.0004 52.16 0.00001 81

BMI Overall 20 825 825 3.10 [2.42, 3.79] <0.00001 46.70 0.001 55

Quality Score >7 10 492 492 2.92 [1.82, 4.02] <0.00001 31.84 0.0004 69

Figure Legends:

Figure 1: Search strategy

Figure 2: Forest Plot demonstrating AHI before and after: (a) Surgical Intervention; (b) Non-Surgical weight loss intervention

Figure 3: Forest Plot demonstrating BMI before and after: (c) Surgical Intervention; (d) Non-Surgical weight loss intervention.

References

1. World_Health_Organization. Obesity and overweight, WHO Fact sheet N°311

(http://www.who.int/mediacentre/factsheets/fs311/en/). 2014.

2. World_Health_Organization. Chronic Respiratory Diseases

(http://www.who.int/gard/publications/chronic_respiratory_diseases.pdf). 2013.

3. Lee W, Nagubadi S, Kryger MH, Mokhlesi B. Epidemiology of Obstructive Sleep

Apnea: a Population-based Perspective. Expert review of respiratory medicine. 2008 Jun

1;2(3):349-64. PMID: 19690624.

4. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a

population health perspective. Am J Respir Crit Care Med. 2002 May 1;165(9):1217-39.

Epub 2002/05/07. PMID: 11991871.

5. Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing.

Journal of applied physiology. 2005 Oct;99(4):1592-9. PMID: 16160020.

6. Collop NA. Advances in treatment of obstructive sleep apnea syndrome. Current

treatment options in neurology. 2009 Sep;11(5):340-8. PMID: 19744400.

7. Araghi MH, Chen YF, Jagielski A, Choudhury S, Banerjee D, Hussain S, et al.

Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review

and meta-analysis. Sleep. 2013 Oct;36(10):1553-62, 62A-62E. PMID: 24082315.

8. Anandam A, Akinnusi M, Kufel T, Porhomayon J, El-Solh AA. Effects of dietary

weight loss on obstructive sleep apnea: a meta-analysis. Sleep & breathing = Schlaf &

Atmung. 2013 Mar;17(1):227-34. PMID: 22374151.

9. Ashrafian H, Darzi A, Athanasiou T. Bariatric surgery - can we afford to do it or deny

doing it? Frontline Gastroenterol. 2011 Apr;2(2):82-9. PMID: 23814666.

10. Sarkhosh K, Switzer NJ, El-Hadi M, Birch DW, Shi X, Karmali S. The impact of

bariatric surgery on obstructive sleep apnea: a systematic review. Obes Surg. 2013

Mar;23(3):414-23. PMID: 23299507.

11. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-

analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of

Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000 Apr 19;283(15):2008-

12. Epub 2000/05/02. PMID: 10789670.

12. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic

reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. Epub 2009/07/23.

PMID: 19622551.

13. Busetto L, Enzi G, Inelmen EM, Costa G, Negrin V, Sergi G, et al. Obstructive sleep

apnea syndrome in morbid obesity: effects of intragastric balloon. Chest. 2005

Aug;128(2):618-23. Epub 2005/08/16. PMID: 16100146.

14. Dixon JB, Schachter LM, O'Brien PE. Polysomnography before and after weight loss

in obese patients with severe sleep apnea. Int J Obes (Lond). 2005 Sep;29(9):1048-54. Epub

2005/04/27. PMID: 15852048.

15. Haines KL, Nelson LG, Gonzalez R, Torrella T, Martin T, Kandil A, et al. Objective

evidence that bariatric surgery improves obesity-related obstructive sleep apnea. Surgery.

2007 Mar;141(3):354-8. Epub 2007/03/14. PMID: 17349847.

16. Lettieri CJ, Eliasson AH, Greenburg DL. Persistence of obstructive sleep apnea after

surgical weight loss. J Clin Sleep Med. 2008 Aug 15;4(4):333-8. Epub 2008/09/04. PMID:

18763424.

17. Fredheim JM, Rollheim J, Sandbu R, Hofso D, Omland T, Roislien J, et al.

Obstructive sleep apnea after weight loss: a clinical trial comparing gastric bypass and

intensive lifestyle intervention. J Clin Sleep Med. 2013;9(5):427-32. Epub 2013/05/16.

PMID: 23674932.

18. Pallayova M, Steele KE, Magnuson TH, Schweitzer MA, Smith PL, Patil SP, et al.

Sleep Apnea Determines Soluble TNF-alpha Receptor 2 Response to Massive Weight Loss.

Obes Surg. 2011 Feb 6. Epub 2011/02/08. PMID: 21298510.

19. Pillar G, Peled R, Lavie P. Recurrence of sleep apnea without concomitant weight

increase 7.5 years after weight reduction surgery. Chest. 1994 Dec;106(6):1702-4. Epub

1994/12/01. PMID: 7988187.

20. Poitou C, Coupaye M, Laaban JP, Coussieu C, Bedel JF, Bouillot JL, et al. Serum

amyloid A and obstructive sleep apnea syndrome before and after surgically-induced weight

loss in morbidly obese subjects. Obes Surg. 2006 Nov;16(11):1475-81. Epub 2006/11/30.

PMID: 17132414.

21. Rajala R, Partinen M, Sane T, Pelkonen R, Huikuri K, Seppalainen AM. Obstructive

sleep apnoea syndrome in morbidly obese patients. J Intern Med. 1991 Aug;230(2):125-9.

Epub 1991/08/01. PMID: 1865163.

22. Rasheid S, Banasiak M, Gallagher SF, Lipska A, Kaba S, Ventimiglia D, et al.

Gastric bypass is an effective treatment for obstructive sleep apnea in patients with clinically

significant obesity. Obes Surg. 2003 Feb;13(1):58-61. Epub 2003/03/13. PMID: 12630614.

23. Valencia-Flores M, Orea A, Herrera M, Santiago V, Rebollar V, Castano VA, et al.

Effect of bariatric surgery on obstructive sleep apnea and hypopnea syndrome,

electrocardiogram, and pulmonary arterial pressure. Obes Surg. 2004 Jun-Jul;14(6):755-62.

Epub 2004/08/21. PMID: 15318977.

24. Sugerman HJ, Fairman RP, Sood RK, Engle K, Wolfe L, Kellum JM. Long-term

effects of gastric surgery for treating respiratory insufficiency of obesity. Am J Clin Nutr.

1992 Feb;55(2 Suppl):597S-601S. Epub 1992/02/01. PMID: 1733136.

25. Guardiano SA, Scott JA, Ware JC, Schechner SA. The long-term results of gastric

bypass on indexes of sleep apnea. Chest. 2003 Oct;124(4):1615-9. Epub 2003/10/14. PMID:

14555601.

26. Dixon JB, Schachter LM, O'Brien PE, Jones K, Grima M, Lambert G, et al. Surgical

vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized

controlled trial. JAMA. 2012 Sep 19;308(11):1142-9. Epub 2012/09/20. PMID: 22990273.

27. Tuomilehto H, Gylling H, Peltonen M, Martikainen T, Sahlman J, Kokkarinen J, et

al. Sustained improvement in mild obstructive sleep apnea after a diet- and physical activity-

based lifestyle intervention: postinterventional follow-up. Am J Clin Nutr. 2010

Oct;92(4):688-96. Epub 2010/08/13. PMID: 20702607.

28. Barnes M, Goldsworthy UR, Cary BA, Hill CJ. A diet and exercise program to

improve clinical outcomes in patients with obstructive sleep apnea--a feasibility study. J Clin

Sleep Med. 2009 Oct 15;5(5):409-15. Epub 2009/12/08. PMID: 19961023.

29. Ferland A, Poirier P, Series F. Sibutramine versus continuous positive airway

pressure in obese obstructive sleep apnoea patients. Eur Respir J. 2009 Sep;34(3):694-701.

Epub 2009/04/10. PMID: 19357147.

30. Kansanen M, Vanninen E, Tuunainen A, Pesonen P, Tuononen V, Hartikainen J, et

al. The effect of a very low-calorie diet-induced weight loss on the severity of obstructive

sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea

syndrome. Clin Physiol. 1998 Jul;18(4):377-85. Epub 1998/08/26. PMID: 9715765.

31. Nerfeldt P, Nilsson BY, Mayor L, Udden J, Friberg D. A two-year weight reduction

program in obese sleep apnea patients. J Clin Sleep Med. Oct 15;6(5):479-86. Epub

2010/10/21. PMID: 20957850.

32. Pasquali R, Colella P, Cirignotta F, Mondini S, Gerardi R, Buratti P, et al. Treatment

of obese patients with obstructive sleep apnea syndrome (OSAS): effect of weight loss and

interference of otorhinolaryngoiatric pathology. Int J Obes. 1990 Mar;14(3):207-17. Epub

1990/03/01. PMID: 2341227.

33. Phillips CL, Yee BJ, Trenell MI, Magnussen JS, Wang D, Banerjee D, et al. Changes

in regional adiposity and cardio-metabolic function following a weight loss program with

sibutramine in obese men with obstructive sleep apnea. J Clin Sleep Med. 2009 Oct

15;5(5):416-21. Epub 2009/12/08. PMID: 19961024.

34. Rubinstein I, Colapinto N, Rotstein LE, Brown IG, Hoffstein V. Improvement in

upper airway function after weight loss in patients with obstructive sleep apnea. Am Rev

Respir Dis. 1988 Nov;138(5):1192-5. Epub 1988/11/01. PMID: 3202479.

35. Sampol G, Munoz X, Sagales MT, Marti S, Roca A, Dolors de la Calzada M, et al.

Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome. Eur Respir J.

1998 Nov;12(5):1156-9. Epub 1998/12/24. PMID: 9864013.

36. Suratt PM, McTier RF, Findley LJ, Pohl SL, Wilhoit SC. Changes in breathing and

the pharynx after weight loss in obstructive sleep apnea. Chest. 1987 Oct;92(4):631-7. Epub

1987/10/01. PMID: 3652748.

37. Suratt PM, McTier RF, Findley LJ, Pohl SL, Wilhoit SC. Effect of very-low-calorie

diets with weight loss on obstructive sleep apnea. Am J Clin Nutr. 1992 Jul;56(1

Suppl):182S-4S. Epub 1992/07/01. PMID: 1615880.

38. Foster GD, Borradaile KE, Sanders MH, Millman R, Zammit G, Newman AB, et al.

A randomized study on the effect of weight loss on obstructive sleep apnea among obese

patients with type 2 diabetes: the Sleep AHEAD study. Arch Intern Med. 2009 Sep

28;169(17):1619-26. Epub 2009/09/30. PMID: 19786682.

39. Johansson K, Neovius M, Lagerros YT, Harlid R, Rossner S, Granath F, et al. Effect

of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a

randomised controlled trial. BMJ. 2009;339:b4609. Epub 2009/12/05. PMID: 19959590.

40. Yee BJ, Phillips CL, Banerjee D, Caterson I, Hedner JA, Grunstein RR. The effect of

sibutramine-assisted weight loss in men with obstructive sleep apnoea. Int J Obes (Lond).

2007 Jan;31(1):161-8. Epub 2006/05/03. PMID: 16652122.

41. Schwartz AR, Gold AR, Schubert N, Stryzak A, Wise RA, Permutt S, et al. Effect of

weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis.

1991 Sep;144(3 Pt 1):494-8. Epub 1991/09/01. PMID: 1892285.

42. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg.

2013 Apr;23(4):427-36. PMID: 23338049.

43. Ashrafian H, le Roux CW, Rowland SP, Ali M, Cummin AR, Darzi A, et al.

Metabolic surgery and obstructive sleep apnoea: the protective effects of bariatric procedures.

Thorax. 2012 May;67(5):442-9. PMID: 21709167.

44. Simpson L, Mukherjee S, Cooper MN, Ward KL, Lee JD, Fedson AC, et al. Sex

differences in the association of regional fat distribution with the severity of obstructive sleep

apnea. Sleep. 2010 Apr;33(4):467-74. PMID: 20394315.

45. Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive

sleep apnoea is independently associated with an increased prevalence of metabolic

syndrome. European heart journal. 2004 May;25(9):735-41. PMID: 15120883.

46. Meslier N, Gagnadoux F, Giraud P, Person C, Ouksel H, Urban T, et al. Impaired

glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J.

2003 Jul;22(1):156-60. PMID: 12882466.

47. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-

disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir

Crit Care Med. 2002 Mar 1;165(5):677-82. Epub 2002/03/05. PMID: 11874813.

48. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP.

Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep

disturbance and obesity. J Clin Endocrinol Metab. 1997 May;82(5):1313-6. Epub 1997/05/01.

PMID: 9141509.

49. Punjabi NM, Beamer BA. C-reactive protein is associated with sleep disordered

breathing independent of adiposity. Sleep. 2007 Jan 1;30(1):29-34. Epub 2007/02/22. PMID:

17310862.

50. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, et al. Impact

of weight loss on inflammatory proteins and their association with the insulin resistance

syndrome in morbidly obese patients. Arteriosclerosis, thrombosis, and vascular biology.

2003 Jun 1;23(6):1042-7. Epub 2003/04/26. PMID: 12714437.

51. Calvin AD, Albuquerque FN, Lopez-Jimenez F, Somers VK. Obstructive sleep

apnea, inflammation, and the metabolic syndrome. Metabolic syndrome and related disorders.

2009 Aug;7(4):271-8. PMID: 19344228.

52. Ip MS, Lam KS, Ho C, Tsang KW, Lam W. Serum leptin and vascular risk factors in

obstructive sleep apnea. Chest. 2000 Sep;118(3):580-6. PMID: 10988175.

53. Eun YG, Kim MG, Kwon KH, Shin SY, Cho JS, Kim SW. Short-term effect of

multilevel surgery on adipokines and pro-inflammatory cytokines in patients with obstructive

sleep apnea. Acta oto-laryngologica. 2010 Dec;130(12):1394-8. PMID: 20632906.

54. Birkmeyer JD, Finks JF, O'Reilly A, Oerline M, Carlin AM, Nunn AR, et al. Surgical

skill and complication rates after bariatric surgery. N Engl J Med. 2013 Oct 10;369(15):1434-

42. PMID: 24106936.

55. Longitudinal Assessment of Bariatric Surgery C, Flum DR, Belle SH, King WC,

Wahed AS, Berk P, et al. Perioperative safety in the longitudinal assessment of bariatric

surgery. N Engl J Med. 2009 Jul 30;361(5):445-54. PMID: 19641201.

56. Driver HS, Taylor SR. Exercise and sleep. Sleep Med Rev. 2000 Aug;4(4):387-402.

PMID: 12531177.

57. Redline S, Budhiraja R, Kapur V, Marcus CL, Mateika JH, Mehra R, et al. The

scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med. 2007 Mar

15;3(2):169-200. PMID: 17557426.

58. Myers KA, Mrkobrada M, Simel DL. Does this patient have obstructive sleep apnea?:

The Rational Clinical Examination systematic review. JAMA. 2013 Aug 21;310(7):731-41.

PMID: 23989984.

59. Harman EM, Wynne JW, Block AJ. The effect of weight loss on sleep-disordered

breathing and oxygen desaturation in morbidly obese men. Chest. 1982 Sep;82(3):291-4.

Epub 1982/09/01. PMID: 7105855.

60. Peiser J, Lavie P, Ovnat A, Charuzi I. Sleep apnea syndrome in the morbidly obese as

an indication for weight reduction surgery. Ann Surg. 1984 Jan;199(1):112-5. Epub

1984/01/01. PMID: 6691724.

61. Charuzi I, Ovnat A, Peiser J, Saltz H, Weitzman S, Lavie P. The effect of surgical

weight reduction on sleep quality in obesity-related sleep apnea syndrome. Surgery. 1985

May;97(5):535-8. Epub 1985/05/01. PMID: 3992478.

62. Charuzi I, Fraser D, Peiser J, Ovnat A, Lavie P. Sleep apnea syndrome in the

morbidly obese undergoing bariatric surgery. Gastroenterol Clin North Am. 1987

Sep;16(3):517-9. Epub 1987/09/01. PMID: 3436659.

63. Summers CL, Stradling JR, Baddeley RM. Treatment of sleep apnoea by vertical

gastroplasty. Br J Surg. 1990 Nov;77(11):1271-2. Epub 1990/11/01. PMID: 2253008.

64. Charuzi I, Lavie P, Peiser J, Peled R. Bariatric surgery in morbidly obese sleep-apnea

patients: short- and long-term follow-up. Am J Clin Nutr. 1992 Feb;55(2 Suppl):594S-6S.

Epub 1992/02/01. PMID: 1733135.

65. Noseda A, Kempenaers C, Kerkhofs M, Houben JJ, Linkowski P. Sleep apnea after 1

year domiciliary nasal-continuous positive airway pressure and attempted weight reduction.

Potential for weaning from continuous positive airway pressure. Chest. 1996 Jan;109(1):138-

43. Epub 1996/01/01. PMID: 8549176.

66. Scheuller M, Weider D. Bariatric surgery for treatment of sleep apnea syndrome in 15

morbidly obese patients: long-term results. Otolaryngol Head Neck Surg. 2001

Oct;125(4):299-302. Epub 2001/10/11. PMID: 11593162.

67. Lankford DA, Proctor CD, Richard R. Continuous positive airway pressure (CPAP)

changes in bariatric surgery patients undergoing rapid weight loss. Obes Surg. 2005

Mar;15(3):336-41. Epub 2005/04/14. PMID: 15826465.

68. Kalra M, Inge T, Garcia V, Daniels S, Lawson L, Curti R, et al. Obstructive sleep

apnea in extremely overweight adolescents undergoing bariatric surgery. Obes Res. 2005

Jul;13(7):1175-9. Epub 2005/08/04. PMID: 16076986.

69. Grunstein RR, Stenlof K, Hedner JA, Peltonen M, Karason K, Sjostrom L. Two year

reduction in sleep apnea symptoms and associated diabetes incidence after weight loss in

severe obesity. Sleep. 2007 Jun 1;30(6):703-10. Epub 2007/06/22. PMID: 17580591.

70. Fritscher LG, Canani S, Mottin CC, Fritscher CC, Berleze D, Chapman K, et al.

Bariatric surgery in the treatment of obstructive sleep apnea in morbidly obese patients.

Respiration. 2007;74(6):647-52. Epub 2007/08/31. PMID: 17728530.

71. Marti-Valeri C, Sabate A, Masdevall C, Dalmau A. Improvement of associated

respiratory problems in morbidly obese patients after open Roux-en-Y gastric bypass. Obes

Surg. 2007 Aug;17(8):1102-10. Epub 2007/10/24. PMID: 17953247.

72. Varela JE, Hinojosa MW, Nguyen NT. Resolution of obstructive sleep apnea after

laparoscopic gastric bypass. Obes Surg. 2007 Oct;17(10):1279-82. Epub 2007/11/15. PMID:

18000730.

73. Kuzniar TJ, Morgenthaler TI. A patient with obstructive sleep apnea undergoing

bariatric surgery. J Clin Sleep Med. 2008 Jun 15;4(3):279-80. Epub 2008/07/04. PMID:

18595442.

74. Rao A, Tey BH, Ramalingam G, Poh AG. Obstructive sleep apnoea (OSA) patterns

in bariatric surgical practice and response of OSA to weight loss after laparoscopic adjustable

gastric banding (LAGB). Ann Acad Med Singapore. 2009 Jul;38(7):587-7. Epub 2009/08/05.

PMID: 19652849.

75. Smith PL, Gold AR, Meyers DA, Haponik EF, Bleecker ER. Weight loss in mildly to

moderately obese patients with obstructive sleep apnea. Ann Intern Med. 1985 Dec;103(6 ( Pt

1)):850-5. Epub 1985/12/01. PMID: 3933396.

76. Kiselak J, Clark M, Pera V, Rosenberg C, Redline S. The association between

hypertension and sleep apnea in obese patients. Chest. 1993 Sep;104(3):775-80. Epub

1993/09/01. PMID: 8365288.

77. Nahmias J, Kirschner M, Karetzky MS. Weight loss and OSA and pulmonary

function in obesity. N J Med. 1993 Jan;90(1):48-53. Epub 1993/01/01. PMID: 8419857.

78. Martinez D, Basile BR. Sibutramine does not worsen sleep apnea syndrome: a

randomized double-blind placebo-controlled study. Sleep Med. 2005 Sep;6(5):467-70. Epub

2005/08/16. PMID: 16099715.

79. Verhulst SL, Franckx H, Van Gaal L, De Backer W, Desager K. The effect of weight

loss on sleep-disordered breathing in obese teenagers. Obesity (Silver Spring). 2009

Jun;17(6):1178-83. Epub 2009/03/07. PMID: 19265797.