Effect of exercise training on sleep apnea: A systematic review and meta-analysis

Open ArchivePublished:May 21, 2016DOI:https://doi.org/10.1016/j.rmed.2016.05.015

      Highlights

      • Exercise as the sole intervention is associated with improved clinical outcomes in patients with Obstructive Sleep Apnea.
      • Exercise as the sole intervention improves AHI in patients with Obstructive Sleep Apnea.
      • Our meta-analysis represents the most recent literature on OSA and exercise.

      Abstract

      Introduction

      Obstructive sleep apnea (OSA) is difficult to manage for those who are intolerant or noncompliant with standard facial mask treatment options. Current treatment options do not address the underlying cause of OSA. Exercise as a treatment option has been found to improve OSA indices.

      Study objectives

      To assess the efficacy of exercise on apnea/hypopnea index (AHI) in adult patients with OSA via a systematic review and meta-analysis. Additional objectives included evaluation of other indices of OSA and well-being in patients after completing an exercise regimen.

      Measurements and results

      Web of Science, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials were searched based on a priori criteria of all studies evaluating the effect of an exercise program on various sleep apnea indices. Both PRISMA statement and MOOSE consensus statement were adhered to. Eight Articles (182 participants) were included: a meta-analysis using a random effects model showed, a decrease in AHI (unstandardized mean difference [USMD], −0.536, 95% confidence interval [CI], −0.865 to −0.206, I2, 20%), reduced Epworth sleepiness scale (ESS) (USMD, −1.246, 95% CI, −2.397 to −0.0953, I2, 0%), and lower body mass index (BMI) (USMD, −0.0473, 95% CI, −0.0375 to 0.280, I2, 0%), in patients receiving exercise as treatment. Relative risks (RR) and odds ratios (OR) showed decreases in AHI (OR: 72.33, 95% CI, 27.906 to 187.491, RR: 7.294, 95% CI, 4.072 to 13.065) in patients receiving exercise as treatment.

      Conclusion

      Among adult patients with OSA, exercise as the sole intervention was associated with improved clinical outcomes.

      Keywords

      1. Introduction

      Obstructive sleep apnea (OSA) is commonly characterized by recurring upper airway obstruction during sleep [
      • Kuna S.T.
      • Sant’Ambrogio G.
      PAthophysiology of upper airway closure during sleep.
      ]. Common predisposing factors for OSA include gender (male), craniofacial anomalies [
      • Myers K.A.
      • Mrkobrada M.
      • Simel D.L.
      Does this patient have obstructive sleep apnea?: the rational clinical examination systematic review.
      ], and obesity [
      • Nahmias J.
      • Kirschner M.
      • Karetzky M.S.
      Weight loss and OSA and pulmonary function in obesity.
      ]. Many health consequences are associated with OSA, including lethargy, memory loss, problems with thinking and judgment [
      • 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.
      ], disruption of normal metabolic functions [
      • Cortelli P.
      • Parchi P.
      • Sforza E.
      • Contin M.
      • Pierangeli G.
      • Barletta G.
      • et al.
      Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome.
      ], and cardiovascular disorders [
      • Sachs C.
      • Kaijser L.
      Autonomic regulation of cardiopulmonary functions in sleep apnea syndrome and narcolepsy.
      ,
      • Shamsuzzaman A.M.
      • Gersh B.J.
      • Somers V.K.
      Obstructive sleep apnea: implications for cardiac and vascular disease.
      ].
      The measure of the severity of OSA is based on the number of apnea or hypopnea events per hour of sleep represented as apnea hypopnea index (AHI). Previous literature has established parameters for OSA; none/minimal OSA diagnosed as AHI <5 per hour, mild OSA diagnosed as AHI ≥5 and AHI <15, moderate OSA diagnosed as AHI ≥15 and AHI <30, and severe OSA diagnosed as AHI ≥30 [
      • Myers K.A.
      • Mrkobrada M.
      • Simel D.L.
      Does this patient have obstructive sleep apnea?: the rational clinical examination systematic review.
      ]. The exact etiology of OSA is unknown and has led to multiple treatment and management options [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ]. Previous studies have evaluated treating OSA symptoms via continuous positive airway pressure (CPAP) [
      • Sawyer A.M.
      • Gooneratne N.S.
      • Marcus C.L.
      • Ofer D.
      • Richards K.C.
      • Weaver T.E.
      A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions.
      ], mandibular adjustment [
      • Mehta A.
      • Qian J.
      • Petocz P.
      • Darendeliler M.A.
      • Cistulli P.A.
      A randomized, controlled study of a mandibular advancement splint for obstructive sleep apnea.
      ,
      • Osullivan R.
      • Hillman D.
      • Mateljan R.
      • Pantin C.
      • Finucane K.
      Mandibular advancement splint – an appliance to treat snoring and obstructive sleep-apnea.
      ], weight loss via diet [
      • 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.
      ,
      • Papandreou C.
      • Schiza S.E.
      • Bouloukaki I.
      • Hatzis C.M.
      • Kafatos A.G.
      • Siafakas N.M.
      • et al.
      Effect of Mediterranean diet versus prudent diet combined with physical activity on OSAS: a randomised trial.
      ], bariatric surgery [
      • Buchwald H.
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      • Pories W.
      • Fahrbach K.
      • et al.
      Bariatric surgery: a systematic review and meta-analysis.
      ,
      • Charuzi I.
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      ,
      • Dixon J.B.
      • Schachter L.M.
      • O’Brien P.E.
      • et al.
      Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial.
      ], pharmacotherapy [
      • Latshang T.D.
      • Nussbaumer-Ochsner Y.
      • Henn R.M.
      • et al.
      Effect of acetazolamide and autocpap therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial.
      ,
      • Strohl K.P.
      • Hensley M.J.
      • Saunders N.A.
      • Scharf S.M.
      • Brown R.
      • Ingram R.H.
      • et al.
      PRogesterone administration and progressive sleep apneas.
      ,
      • White D.
      • Zwillich C.
      • Pickett C.
      • Douglas N.
      • Findley L.
      • Weil J.
      Central sleep-apnea – improvement with acetazolamide therapy.
      ], and upper airway surgery [
      • Chai-Coetzer C.
      • Antic N.A.
      • Rowland L.
      • et al.
      Primary care vs specialist sleep center management of obstructive sleep apnea and daytime sleepiness and quality of life: a randomized trial.
      ,
      • Elshaug A.G.
      • Moss J.R.
      • Southcott A.M.
      • Hiller J.E.
      Redefining success in airway surgery for obstructive sleep apnea: a meta analysis and synthesis of the evidence.
      ,
      • Lin H.-C.
      • Friedman M.
      • Chang H.-W.
      • Gurpinar B.
      The efficacy of multilevel surgery of the upper airway in adults with obstructive sleep apnea/hypopnea syndrome.
      ]. However, long-term studies have shown that the therapeutic efficacy of these treatments do not address the underlying cause of OSA, evident by the AHI reduction then resurgence in AHI of participants who underwent treatment by CPAP [
      • Sawyer A.M.
      • Gooneratne N.S.
      • Marcus C.L.
      • Ofer D.
      • Richards K.C.
      • Weaver T.E.
      A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions.
      ], weight loss via reduced calorie intake [
      • Sampol G.
      • Muñoz X.
      • Sagalés M.T.
      • Martí S.
      • Roca A.
      • Dolors de la Calzada M.
      • et al.
      Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome.
      ,
      • Suratt P.M.
      • McTier R.F.
      • Findley L.J.
      • Pohl S.L.
      • Wilhoit S.C.
      Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.
      ], bariatric surgery [
      • Charuzi I.
      • Lavie P.
      • Peiser J.
      • Peled R.
      Bariatric surgery in morbidly obese sleep-apnea patients – short-term and long-term follow-up.
      ], and mandibular adjustment [
      • Mehta A.
      • Qian J.
      • Petocz P.
      • Darendeliler M.A.
      • Cistulli P.A.
      A randomized, controlled study of a mandibular advancement splint for obstructive sleep apnea.
      ,
      • Osullivan R.
      • Hillman D.
      • Mateljan R.
      • Pantin C.
      • Finucane K.
      Mandibular advancement splint – an appliance to treat snoring and obstructive sleep-apnea.
      ,
      • Clark G.
      • Arand D.
      • Chung E.
      • Tong D.
      Effect of anterior mandibular positioning on obstructive sleep-apnea.
      ].
      Exercise programs to treat and manage OSA in patients have displayed promising results in reducing AHI and Epworth Sleepiness Scale (ESS) [
      • Alves Eda S.
      • Ackel-D’Elia C.
      • Luz G.P.
      • Cunha T.C.A.
      • Carneiro G.
      • Tufik S.
      • et al.
      Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?.
      ,
      • Pendharkar S.R.
      • Tsai W.H.
      • Eves N.D.
      • Ford G.T.
      • Davidson W.J.
      CPAP increases exercise tolerance in obese subjects with obstructive sleep apnea.
      ,
      • Ucok K.
      • Aycicek A.
      • Sezer M.
      • Genc A.
      • Akkaya M.
      • Caglar V.
      • et al.
      Aerobic and anaerobic exercise capacities in obstructive sleep apnea and associations with subcutaneous fat distributions.
      ,
      • Vanhecke T.E.
      • Franklin B.A.
      • Ajluni S.C.
      • Sangal R.B.
      • McCullough P.A.
      Cardiorespiratory fitness and sleep-related breathing disorders.
      ,
      • West S.D.
      • Kohler M.
      • Nicoll D.J.
      • Stradling J.R.
      The effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: a randomised controlled trial.
      ]. Further, exercise has been shown to reduce the severity of other disorders and/or diseases associated with OSA including diabetes [

      Sigal RJ, Kenny Gp Fau – Boule NG, Boule Ng Fau – Wells GA, Wells Ga Fau – Prud’homme D, Prud’homme D Fau – Fortier M, Fortier M Fau – Reid RD, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial.

      ], cardiovascular disease [

      Vanhees L, Rauch B Fau – Piepoli M, Piepoli M Fau – van Buuren F, van Buuren F Fau – Takken T, Takken T Fau – Borjesson M, Borjesson M Fau – Bjarnason-Wehrens B, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III).

      ], hypertension [

      Lackland DT, Voeks JH. Metabolic syndrome and hypertension: regular exercise as part of lifestyle management.

      ], and obesity [

      Clark JE. Diet, exercise or diet with exercise: comparing the effectiveness of treatment options for weight-loss and changes in fitness for adults (18–65 years old) who are overfat, or obese; systematic review and meta-analysis.

      ]. It is not fully understood how exercise reduces OSA symptoms, but previous reviews have indicated that the impact of exercise on OSA is not related to reduction of body weight or body mass index (BMI) in both epidemiologic [

      Punjabi NM. The epidemiology of adult obstructive sleep apnea.

      ] and experimental studies [
      • Awad K.M.
      • Malhotra A.
      • Barnet J.H.
      • Quan S.F.
      • Peppard P.E.
      Exercise is associated with a reduced incidence of sleep-disordered breathing.
      ,
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ,
      • Peppard P.E.
      • Young T.
      Exercise and sleep-disordered breathing: an association independent of body habitus.
      ].
      Previous reviews and meta-analyses evaluated different treatments on OSA patients: diet and lifestyle [
      • Thomasouli M.-A.
      • Brady E.M.
      • Davies M.J.
      • Hall A.P.
      • Khunti K.
      • Morris D.H.
      • et al.
      The impact of diet and lifestyle management strategies for obstructive sleep apnoea in adults: a systematic review and meta-analysis of randomised controlled trials.
      ], supervised exercise [
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ], diet or diet and exercise [
      • Anandam A.
      • Akinnusi M.
      • Kufel T.
      • Porhomayon J.
      • El-Solh A.A.
      Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
      ], diet and/or supervised exercise [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ], and intensive lifestyle intervention (low calorie or very low calorie diet, mandibular advancement) [
      • Mitchell L.J.
      • Davidson Z.E.
      • Bonham M.
      • O’Driscoll D.M.
      • Hamilton G.S.
      • Truby H.
      Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis.
      ]. Additionally, in the literature we found studies that were excluded from previous reviews because the exercise programs were initially led by professionals and study personnel (supervised exercise programs), but ended as unsupervised exercise programs where the participants were solely responsible for their treatment [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ].
      The primary objective was to study the use of exercise (supervised and unsupervised) as management treatment for OSA by analyzing the difference in pre- and post-intervention AHI in adult patients with OSA. Secondary objectives included evaluating the effects of exercise on ESS, BMI.

      2. Materials and methods

      Five authors (K.A., B.N., A.S., F.M., and M.M) identified studies in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1993–2014), Web of Science (WOS), and CINAHL. The following search strategy was used: ([text word] exercise OR [text word] exercise program OR [text word] aerobic exercise OR [text word] physical activity OR [text word] muscle stretching exercise OR [text word] plyometric exercise OR [text word] resistance training OR [text word] running OR [text word] jogging OR [text word] swimming OR [text word] isometric exercise OR [text word] weightlifting OR [text word] weightbearing AND [text word] sleep apnea OR [text word] obstructive sleep apnea OR [text word] sleep disturbed breathing. All reviewed articles and cross-referenced studies were screened for relevant data. Reference lists of included studies and previously published systematic reviews and meta-analyses on OSA and lifestyle interventions were hand searched. No language restrictions were applied. Any disagreement was resolved by consensus. All reviewed articles and cross-referenced studies were screened for relevant data. Authors also searched previously published studies, reviews, and meta-analyses on OSA and lifestyle interventions [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ,
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ,
      • Thomasouli M.-A.
      • Brady E.M.
      • Davies M.J.
      • Hall A.P.
      • Khunti K.
      • Morris D.H.
      • et al.
      The impact of diet and lifestyle management strategies for obstructive sleep apnoea in adults: a systematic review and meta-analysis of randomised controlled trials.
      ,
      • Anandam A.
      • Akinnusi M.
      • Kufel T.
      • Porhomayon J.
      • El-Solh A.A.
      Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
      ,
      • Mitchell L.J.
      • Davidson Z.E.
      • Bonham M.
      • O’Driscoll D.M.
      • Hamilton G.S.
      • Truby H.
      Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis.
      ,
      • Shneerson J.
      • Wright J.
      Lifestyle modification for obstructive sleep apnoea.
      ]. In the case of missing data, authors were contacted for additional unpublished data in order to complete the data set [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ]. Inclusion criteria included: adult participants (age >18 years), OSA was diagnosed via polysomnography (PSG) via AHI ≥5, exercise program duration ≥2 months, frequency of exercise ≥2 sessions per week, exercise session ≥30 min, exercise as the sole intervention, patient cohort ≥9, and pre- and post-intervention changes in AHI, BMI, and ESS were reported. Randomized trials as well as observational studies were included with no restrictions on language or supervised or unsupervised exercise program.
      Articles were excluded if OSA was not diagnosed via PSG, treatment was a combination of exercise and lifestyle intervention, subjects were diagnosed with heart failure (HF), neuromuscular disorders (NMD), and/or chronic pulmonary disease (COPD), were using dental sleep devices, and/or patients previously had undergone surgery. The Jadad score provides points for randomization (2), blinding (2), and patient dropouts (1), and was used to quality score and evaluate all randomized controlled trials (RCTs) (Fig. 1) [
      • Jadad A.R.
      • Moore R.A.
      • Carroll D.
      • Jenkinson C.
      • Reynolds D.J.
      • Gavaghan D.J.
      • et al.
      Assessing the quality of reports of randomized clinical trials: is blinding necessary?.
      ]. The information collected from the relevant studies included: sampling framework(s), author(s), year article was published in journal (not e-pub date), PSG data, mean of cohort age, exercise duration, exercise frequency, exercise protocol, keywords, CPAP usage, and pre- and post-intervention AHI, ESS, BMI, profile of mood states, and well-being or quality of life question. The mean differences of AHI, BMI, ESS for pre- and post-intervention for both treatment and control groups were extracted for each study and graphically represented using forest plot graphs; this data was pooled using USMD due to the uniformity of scale and analysis [
      • Borenstein M.
      • Hedges L.V.
      • Higgins J.
      • Rothstein H.R.
      A basic introduction to fixed-effect and random-effects models for meta-analysis.
      ] (Fig. 2). Two authors (K.A., B.C.) conducted independent statistical analysis to confirm the results. Heterogeneity was assessed using I2 statistics and Cochrane’s Q statistic [
      • Higgins J.P.T.
      • Thompson S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      ].
      Figure thumbnail gr1
      Fig. 1Baseline Characteristics of the Studies Included in the Final Meta-Analysis. *Mean represented here is separated via exercise or control group and by each individual study. Abbreviations: BMI = body mass index; SD = standard deviation; ESS = Epworth Sleep Scale; AHI = apnea hypopnea index; RDI = respiratory disturbance index; RCT = randomized controlled trial.
      Figure thumbnail gr2
      Fig. 2Mean change in AHI, ESS, and BMI from baseline to end of treatment showing a decrease in AHI (unstandardized mean difference [USMD], −0.536, 95% confidence interval ([CI], −0.865 to −0.206, I2, 20%), reduced Epworth sleepiness scale (ESS) (USMD, −1.246, 95% CI, −2.397 to −0.0953, I2, 0%), and lower body mass index (BMI) (USMD, −0.0473, 95% CI, −0.0375 to 0.280, I2, 0%), in patients receiving exercise as treatment. Abbreviations: BMI, Body Mass Index, SMD standardized mean difference, ESS, Epworth Sleep Scale, AHI, apnea hypopnea index, CI, confidence interval, N1, experimental group pre-intervention, N2, experimental group post intervention.
      The parametric variables AHI, BMI, and ESS were represented as the mean and standard deviation despite the small sample sizes. To check for publication bias, funnel plots of effect size and standard error were constructed [
      • Sterne J.A.
      • Egger M.
      Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.
      ]. Funnel plots analyzed using the Begg and Mazumdar rank correlation test did not suggest significant publication bias for the analysis conducted [
      • Sterne J.A.C.
      • Egger M.
      • Smith G.D.
      Investigating and dealing with publication and other biases in meta-analysis.
      ]. Both the PRISMA criteria [
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gøtzsche P.C.
      • Ioannidis J.P.A.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
      ], and the MOOSE guidelines [
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • et al.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting.
      ] were followed (Fig. 3). All analyses were performed using MedCalc® (http://www.medcalc.org/) and R programming language. P-values less than 0.10 were considered significant based on the literature recommended threshold [
      • Lau J.
      • Ioannidis J.P.
      • Schmid C.H.
      Quantitative synthesis in systematic reviews.
      ].
      Figure thumbnail gr3
      Fig. 3MOOSE Guidelines Checklist. Abbreviations: AHI = apnea/hypopnea index; ESS = Epworth sleepiness scale; BMI = body mass index.

      3. Results

      The initial search yielded 8394 studies (6776 from MEDLINE, 308 from CENTRAL, 291 from CINAHL, and 1019 from WOS). After removing 812 duplicates, we conducted a title and abstract search in the remaining 7582 articles, which resulted in 1142 studies. After evaluating the abstracts of each study, we excluded 1126 studies for failing to the priori inclusion/exclusion criteria. Eight articles were excluded after a close reading of the text. The final analysis consisted of 8 articles and 180 participants [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Netzer N.C.
      • Hoegel J.J.
      • Loube D.
      • Netzer C.M.
      • Hay B.
      • Alvarez-Sala R.
      • et al.
      Prevalence of symptoms and risk of sleep apnea in primary care.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] (Fig. 4). Seven references had pre- and post-intervention data for AHI and BMI [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ], 5 studies included AHI and BMI data but were missing ESS data (Fig. 1). The most complete data set was used for analysis in the instance of duplicate reports or articles [
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ]. Variance between studies was accounted for by using fixed and random effects methods meta-analyses [
      • Armitage P.
      • Berry G.
      • Matthews J.N.S.
      Statistical Methods in Medical Research.
      ].
      Figure thumbnail gr4
      Fig. 4Study Selection for the Effect of Exercise on Patients with Obstructive Sleep Apnea. CENTRAL, Cochrane Central Register of Controlled Trials; CINAHL, Cumulative Index to Nursing and Allied Health Literature, WOS, Web of Science, HF, Heart Failure, COPD, chronic pulmonary disease, NMD, neuromuscular disorder, OSA, obstructive sleep apnea, PSG, polysomnograph.
      Studies’ baseline data including publication year, study design, total number of subjects, duration of exercise program, number of participants (% of males and females), age, and pre- and post-intervention BMI, AHI, and ESS were extracted. Six studies were RCTs [
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] and 2 studies were single group intervention studies [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Netzer N.C.
      • Hoegel J.J.
      • Loube D.
      • Netzer C.M.
      • Hay B.
      • Alvarez-Sala R.
      • et al.
      Prevalence of symptoms and risk of sleep apnea in primary care.
      ]. Both supervised and unsupervised exercise programs were used as treatment in the studies. Supervised exercise programs were used in 6 studies [
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Netzer N.C.
      • Hoegel J.J.
      • Loube D.
      • Netzer C.M.
      • Hay B.
      • Alvarez-Sala R.
      • et al.
      Prevalence of symptoms and risk of sleep apnea in primary care.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] and unsupervised exercise programs in 2 studies [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ]. Treatment duration ranged from 2 months to 6 months. Treatment frequency ranged from 2 days a week to 7 days a week, from 30 min to 150 min each session. Exercise protocols ranged from aerobic exercise, e.g. walking/running on treadmill, stair climbing, Airdyne® machine, stationary bicycle, resistance training, and oropharyngeal exercises. Participants’ ages ranged from 32.2 to 54.4 years.
      A total of 7 studies [
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] compared mean AHI scores pre- and post-intervention for a control group and experimental group. One study [
      • Giebelhaus V.
      • Strohl K.P.
      • Lormes W.
      • Lehmann M.
      • Netzer N.
      Physical exercise as an adjunct therapy in sleep apnea-an open trial.
      ] that measured respiratory disturbance index (RDI) was not included in the AHI meta-analysis. Comparison of the 2 groups found exercise was associated with a reduction in AHI after treatment (unstandardized mean difference [USMD], −0.536, 95% CI, −0.865 to −0.206, I2, 20%). A total of 4 studies [
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] compared mean ESS scores pre- and post-intervention for a control group and experimental group. Exercise was associated with having a lower decrease in the total ESS after treatment (USMD, −1.246, 95% CI, −2.397 to −0.0953, I2, 0%). A total of 4 studies [
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Kline C.E.
      • Crowley E.P.
      • Ewing G.B.
      • Burch J.B.
      • Blair S.N.
      • Durstine J.L.
      • et al.
      The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ] compared mean BMI scores pre- and post-intervention for a control group and experimental group. Exercise was not found to have statistically significant effect on BMI (USMD, −0.0473, 95% CI, −0.0375 to 0.280, I2, 0%).
      Due to the results assessing AHI excluding RDI, an analysis was performed that excluded the study that measured pre- and post-intervention RDI only, fixed effects model ([USMD], −0.510, 95% CI, −0.783 to −0.237, I2, 7%, p, <0.001), random effects model ([USMD], −0.515, 95% CI, −0.800 to −0.230, I2, 7%, p, <0.001). Similar results were found when risk ratio (RR) and odds ratio (OR) were used to compare pre- and post-intervention results concerning AHI. Patients receiving exercise treatment had an AHI decrease of 4 when compared to patients not receiving exercise treatment (OR: 72.33, 95% CI, 27.906 to 187.491; RR: 7.294, 95% CI, 4.072).

      4. Discussion

      In this study, mean treatment outcomes of pre- and post-intervention data from 8 studies with 180 total participants were compared. The main findings highlight that exercise has an effect on reducing both AHI and ESS in patients with OSA. This conclusion remained consistent independent of different types of exercise, durations of exercise, frequency of exercise sessions, CPAP usage, and supervised or unsupervised treatment programs. This conclusion was supported via the moderate sample size and degree of heterogeneity.
      A potential explanation cited for exercise reducing AHI in mild or severe OSA focuses on the comorbidity of obesity and OSA [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ,
      • Anandam A.
      • Akinnusi M.
      • Kufel T.
      • Porhomayon J.
      • El-Solh A.A.
      Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
      ]. Excess adipose tissue is the cause of the airway collapsing and apnea or hypopnea events occurring, and obesity is linked to increased adipose tissue in the pharyngeal airway [
      • Kuna S.T.
      • Sant’Ambrogio G.
      PAthophysiology of upper airway closure during sleep.
      ,
      • Myers K.A.
      • Mrkobrada M.
      • Simel D.L.
      Does this patient have obstructive sleep apnea?: the rational clinical examination systematic review.
      ,
      • Nahmias J.
      • Kirschner M.
      • Karetzky M.S.
      Weight loss and OSA and pulmonary function in obesity.
      ,
      • Peppard P.E.
      • Young T.
      Exercise and sleep-disordered breathing: an association independent of body habitus.
      ,
      • Young T.
      • Peppard P.E.
      • Gottlieb D.J.
      Epidemiology of obstructive sleep apnea – a population health perspective.
      ]. Exercise can lead to weight loss and reduction in BMI [
      • Thomasouli M.-A.
      • Brady E.M.
      • Davies M.J.
      • Hall A.P.
      • Khunti K.
      • Morris D.H.
      • et al.
      The impact of diet and lifestyle management strategies for obstructive sleep apnoea in adults: a systematic review and meta-analysis of randomised controlled trials.
      ], and studies have suggested that reduction in BMI is associated with reduction in the volume of adipose tissue in the pharyngeal airway [
      • Greenburg D.L.
      • Lettieri C.J.
      • Eliasson A.H.
      Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis.
      ]. However, our results support Iftikhar et al.’s [
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ] findings that exercise reduces AHI regardless of significant reduction in BMI. Previous studies have shown dramatic AHI reduction through low calorie diet [
      • 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.
      ,
      • Suratt P.M.
      • McTier R.F.
      • Findley L.J.
      • Pohl S.L.
      • Wilhoit S.C.
      Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.
      ,
      • Anandam A.
      • Akinnusi M.
      • Kufel T.
      • Porhomayon J.
      • El-Solh A.A.
      Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
      ] or diet modification [
      • Papandreou C.
      • Schiza S.E.
      • Bouloukaki I.
      • Hatzis C.M.
      • Kafatos A.G.
      • Siafakas N.M.
      • et al.
      Effect of Mediterranean diet versus prudent diet combined with physical activity on OSAS: a randomised trial.
      ,
      • Sampol G.
      • Muñoz X.
      • Sagalés M.T.
      • Martí S.
      • Roca A.
      • Dolors de la Calzada M.
      • et al.
      Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome.
      ,
      • Nerfeldt P.
      • Nilsson B.Y.
      • Mayor L.
      • Udden J.
      • Friberg D.
      A two-year weight reduction program in obese sleep apnea patients.
      ], pharmacological treatment [
      • Latshang T.D.
      • Nussbaumer-Ochsner Y.
      • Henn R.M.
      • et al.
      Effect of acetazolamide and autocpap therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial.
      ,
      • Strohl K.P.
      • Hensley M.J.
      • Saunders N.A.
      • Scharf S.M.
      • Brown R.
      • Ingram R.H.
      • et al.
      PRogesterone administration and progressive sleep apneas.
      ,
      • White D.
      • Zwillich C.
      • Pickett C.
      • Douglas N.
      • Findley L.
      • Weil J.
      Central sleep-apnea – improvement with acetazolamide therapy.
      ], exercise and lifestyle intervention [
      • Mitchell L.J.
      • Davidson Z.E.
      • Bonham M.
      • O’Driscoll D.M.
      • Hamilton G.S.
      • Truby H.
      Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis.
      ,
      • Shneerson J.
      • Wright J.
      Lifestyle modification for obstructive sleep apnoea.
      ], and surgery [
      • Charuzi I.
      • Lavie P.
      • Peiser J.
      • Peled R.
      Bariatric surgery in morbidly obese sleep-apnea patients – short-term and long-term follow-up.
      ,
      • Dixon J.B.
      • Schachter L.M.
      • O’Brien P.E.
      • et al.
      Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial.
      ,
      • Lin H.-C.
      • Friedman M.
      • Chang H.-W.
      • Gurpinar B.
      The efficacy of multilevel surgery of the upper airway in adults with obstructive sleep apnea/hypopnea syndrome.
      ,
      • Greenburg D.L.
      • Lettieri C.J.
      • Eliasson A.H.
      Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis.
      ]. Though, as already mentioned, follow-up studies have shown that some of these treatments do not lead to long-term reduction in AHI [
      • Sawyer A.M.
      • Gooneratne N.S.
      • Marcus C.L.
      • Ofer D.
      • Richards K.C.
      • Weaver T.E.
      A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions.
      ,
      • Charuzi I.
      • Lavie P.
      • Peiser J.
      • Peled R.
      Bariatric surgery in morbidly obese sleep-apnea patients – short-term and long-term follow-up.
      ,
      • Sampol G.
      • Muñoz X.
      • Sagalés M.T.
      • Martí S.
      • Roca A.
      • Dolors de la Calzada M.
      • et al.
      Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome.
      ,
      • Suratt P.M.
      • McTier R.F.
      • Findley L.J.
      • Pohl S.L.
      • Wilhoit S.C.
      Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.
      ].
      The benefits of systematic reviews and meta-analyses lie in summarizing information and evaluating treatments; however, one of the pitfalls of meta-analyses is the assessing of information and validating methods [
      • Slavin R.E.
      Best evidence synthesis: an intelligent alternative to meta-analysis.
      ]. As previously mentioned, analyses on different characteristics of participants and combination of interventions have been performed: diet and lifestyle by Thomasouli et al. [
      • Thomasouli M.-A.
      • Brady E.M.
      • Davies M.J.
      • Hall A.P.
      • Khunti K.
      • Morris D.H.
      • et al.
      The impact of diet and lifestyle management strategies for obstructive sleep apnoea in adults: a systematic review and meta-analysis of randomised controlled trials.
      ]; supervised exercise as treatment was analyzed by Iftikhar et al. [
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ]; diet or diet and exercise as intervention was analyzed by Anandam et al. [
      • Anandam A.
      • Akinnusi M.
      • Kufel T.
      • Porhomayon J.
      • El-Solh A.A.
      Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
      ]; diet and/or supervised exercise was analyzed by Araghi et al. [
      • Araghi M.H.
      • Chen Y.-F.
      • Jagielski A.
      • Choudhury S.
      • Banerjee D.
      • Hussain S.
      • et al.
      Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
      ]; upper airway muscle tonus by Valbuza [
      • Valbuza J.S.
      • de Oliveira M.M.
      • Conti C.F.
      • Prado L.B.F.
      • de Carvalho L.B.C.
      • do Prado G.F.
      Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.
      ]; and intensive lifestyle intervention (low calorie or very low calorie diet, mandibular advancement) by Mitchell et al. [
      • Mitchell L.J.
      • Davidson Z.E.
      • Bonham M.
      • O’Driscoll D.M.
      • Hamilton G.S.
      • Truby H.
      Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis.
      ]. In this study, we compared pre- and post-intervention standard mean difference of AHI, BMI, and ESS and found that reduction in OSA indices were similar regardless of the exercise protocol used. Due to the similarity in results we cannot say which protocol, duration, or frequency were the best [
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gøtzsche P.C.
      • Ioannidis J.P.A.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
      ]; however, our results raise important questions about OSA treatment and management options. The possible implications for treatment and management of OSA from this study are: (1) exercise as the primary treatment and management option for OSA; (2) the use of unsupervised exercise or telemedicine treatment for OSA; and (3) the use of low-calorie diets and surgical interventions may not be required. These conclusions are consistent with the growing body of studies that focus on exercise as treatment for OSA is effective in reducing OSA indices [
      • Papandreou C.
      • Schiza S.E.
      • Bouloukaki I.
      • Hatzis C.M.
      • Kafatos A.G.
      • Siafakas N.M.
      • et al.
      Effect of Mediterranean diet versus prudent diet combined with physical activity on OSAS: a randomised trial.
      ,
      • Alves Eda S.
      • Ackel-D’Elia C.
      • Luz G.P.
      • Cunha T.C.A.
      • Carneiro G.
      • Tufik S.
      • et al.
      Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?.
      ,
      • Pendharkar S.R.
      • Tsai W.H.
      • Eves N.D.
      • Ford G.T.
      • Davidson W.J.
      CPAP increases exercise tolerance in obese subjects with obstructive sleep apnea.
      ,
      • Ucok K.
      • Aycicek A.
      • Sezer M.
      • Genc A.
      • Akkaya M.
      • Caglar V.
      • et al.
      Aerobic and anaerobic exercise capacities in obstructive sleep apnea and associations with subcutaneous fat distributions.
      ,
      • Iftikhar I.H.
      • Kline C.E.
      • Youngstedt S.D.
      Effects of exercise training on sleep apnea: a meta-analysis.
      ,
      • Norman J.F.
      • Von Essen S.G.
      • Fuchs R.H.
      • McElligott M.
      Exercise training effect on obstructive sleep apnea syndrome.
      ,
      • Ackel-D’Elia C.
      • da Silva A.C.
      • Silva R.S.
      • Truksinas E.
      • Sousa B.S.
      • Tufik S.
      • et al.
      Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome.
      ,
      • Cavagnolli D.A.
      • Esteves A.M.
      • Ackel-D’Elia C.
      • Maeda M.Y.
      • de Faria A.P.
      • Tufik S.
      • et al.
      Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea.
      ,
      • Guimarães K.C.
      • Drager L.F.
      • Genta P.R.
      • Marcondes B.F.
      • Lorenzi-Filho G.
      Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome.
      ,
      • Netzer N.C.
      • Hoegel J.J.
      • Loube D.
      • Netzer C.M.
      • Hay B.
      • Alvarez-Sala R.
      • et al.
      Prevalence of symptoms and risk of sleep apnea in primary care.
      ,
      • Schütz T.C.B.
      • Cunha T.C.A.
      • Moura-Guimaraes T.
      • Luz G.P.
      • Ackel-D’Elia C.
      • Alves Eda S.
      • et al.
      Comparison of the effects of continuous positive airway pressure, oral appliance and exercise training in obstructive sleep apnea syndrome.
      ,
      • Sengul Y.S.
      • Ozalevli S.
      • Oztura I.
      • Itil O.
      • Baklan B.
      The effect of exercise on obstructive sleep apnea: a randomized and controlled trial.
      ,
      • Giebelhaus V.
      • Strohl K.P.
      • Lormes W.
      • Lehmann M.
      • Netzer N.
      Physical exercise as an adjunct therapy in sleep apnea-an open trial.
      ]. Thus, possible future research could test exercise as treatment and management of OSA symptoms in non-obese individuals, and continued analyses on the cause of OSA.
      There has been some debate on if the size of the trial impacts treatment outcomes [
      • Borzak S.
      • Ridker P.M.
      Discordance between meta-analyses and large-scale randomized, controlled trials. Examples from the management of acute myocardial infarction.
      ,
      • Flather M.D.
      • Farkouh M.E.
      • Pogue J.M.
      • Yusuf S.
      Strengths and limitations of meta-analysis: larger studies may be more reliable.
      ,
      • LeLorier J.
      • Grégoire G.
      • Benhaddad A.
      • Lapierre J.
      • Derderian F.
      Discrepancies between meta-analyses and subsequent large randomized, controlled trials.
      ]. Specifically, smaller studies had larger treatment outcomes than similar larger more robust trials [
      • Valbuza J.S.
      • de Oliveira M.M.
      • Conti C.F.
      • Prado L.B.F.
      • de Carvalho L.B.C.
      • do Prado G.F.
      Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.
      ,
      • Borzak S.
      • Ridker P.M.
      Discordance between meta-analyses and large-scale randomized, controlled trials. Examples from the management of acute myocardial infarction.
      ]; however, the reason for this phenomenon is unknown and some authors have proposed methods that utilize small studies for use in meta-analysis models [
      • Sterne J.A.C.
      • Egger M.
      • Smith G.D.
      Investigating and dealing with publication and other biases in meta-analysis.
      ,
      • Terrin N.
      • Schmid C.H.
      • Lau J.
      In an empirical evaluation of the funnel plot, researchers could not visually identify publication bias.
      ]. Thus, future research is needed to examine if small trials are correlated with larger treatment.
      It can be argued that in order to accurately determine whether exercise is associated with a reduction in OSA indices, a high number of patients diagnosed with OSA would have to be enrolled in an a RCT, have a low level of attrition, and conduct annual follow-up diagnoses. However, to enroll thousands of patients in a clinical trial of this magnitude would require years and could prove expensive to funding agencies.
      Our meta-analysis represents the most recent literature on OSA and exercise; however, our study selection was restricted by our inclusion and exclusion criteria and was not exhaustively inclusive of all articles or studies on OSA, OSA and exercise, and OSA management. However, future meta-analysis may be conducted on the efficacy of supervised compared to unsupervised exercise as treatment, and a mixed treatment comparison of the current recommendations for management of OSA by The American College of Physicians.

      5. Conclusion

      In this meta-analysis of exercise as the sole treatment for OSA differences in AHI between patients in exercise programs compared to those not enrolled in an exercise program were statistically significant. However, the reduction in OSA indices may need to be further explored via comparison of larger participant numbers, supervised and unsupervised exercise programs, frequency of treatment, treatment duration, and exercise protocols. Though lifestyle intervention, upper airway surgery, mandibular advancement, and CPAP have shown similar decreases in OSA indices, exercise programs as treatment reduce AHI and the underlying causes of OSA.

      Disclosure statement

      This was not an industry supported study. The authors have no conflict of interest or financial involvement with this manuscript.

      Author contributions

      Kenneth D. Aiello had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors made substantial contributions to the study and this manuscript. None were compensated for the manuscript preparation.

      Acknowledgements

      The authors wish to thank Michael Grover DO, Department of Family Medicine, Mayo Clinic Arizona for his insights and guidance.

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