Treating OSA: Current and emerging therapies beyond CPAP

Continuous positive airway pressure (CPAP) is the standard treatment for moderate-to-severe obstructive sleep apnoea (OSA). However, adherence to CPAP is limited and non-CPAP therapies are frequently explored. Oral appliance (OA) therapy is currently widely used for the treatment of snoring, mild, moderate and severe OSA. The most commonly used and studied OA consists of a maxillary and mandibular splint which hold the lower jaw forward during sleep. The efficacy of OA is inferior to CPAP; however, the effectiveness as measured by sleepiness, quality of life, endothelial function and blood pressure is similar likely due to higher acceptance and subjective adherence. Upper airway stimulation augments neural drive by unilaterally stimulating the hypoglossal nerve. The Stimulation Therapy for Apnea Reduction (STAR) study enrolled 126 patients and demonstrated a 68% reduction in OSA severity. A high upfront cost and variable response are the main limitations. Oropharyngeal exercises consist of a set of isometric and isotonic exercises involving the tongue, soft palate and lateral pharyngeal wall. The collective reported trials (n = 120) showed that oropharyngeal exercises can ameliorate OSA and snoring (~30-40%). Nasal EPAP devices consist of disposable one-way resister valve. A systematic review (n = 345) showed that nasal EPAP reduced OSA severity by 53%. The Winx device consists of a mouthpiece placed inside the oral cavity that is connected by tubing to a console that generates negative pressure. Winx may provide successful therapy for ~30-40% of OSA patients. In conclusion, several non-CPAP therapies to treat OSA are currently available.

[1]  Bradley A Edwards,et al.  Positional modification techniques for supine obstructive sleep apnea: A systematic review and meta-analysis. , 2017, Sleep medicine reviews.

[2]  B. Edwards,et al.  The Combination of Supplemental Oxygen and a Hypnotic Markedly Improves Obstructive Sleep Apnea in Patients with a Mild to Moderate Upper Airway Collapsibility. , 2016, Sleep.

[3]  Rui Chen,et al.  CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. , 2016, The New England journal of medicine.

[4]  Dorian Murariu,et al.  Trends in CPAP adherence over twenty years of data collection: a flattened curve , 2016, Journal of Otolaryngology - Head & Neck Surgery.

[5]  Adrian J. Williams,et al.  Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea , 2016, Thorax.

[6]  B. Hofauer,et al.  Nerve monitoring–guided selective hypoglossal nerve stimulation in obstructive sleep apnea patients , 2016, The Laryngoscope.

[7]  C. Kushida,et al.  Nasal Expiratory Positive Airway Pressure Devices (Provent) for OSA: A Systematic Review and Meta-Analysis , 2015, Sleep disorders.

[8]  D. Bratton,et al.  CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. , 2015, JAMA.

[9]  P. Genta,et al.  Effects of Oropharyngeal Exercises on Snoring: A Randomized Trial. , 2015, Chest.

[10]  R. Chervin,et al.  Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015 , 2015 .

[11]  G. Lipman,et al.  Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID). , 2015, High altitude medicine & biology.

[12]  A. Cohen,et al.  Surgical management of OSA in adults. , 2015, Chest.

[13]  C. Kushida,et al.  Myofunctional Therapy to Treat Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. , 2015, Sleep.

[14]  P. Strollo,et al.  Long-Term Cost-Effectiveness of Upper Airway Stimulation for the Treatment of Obstructive Sleep Apnea: A Model-Based Projection Based on the STAR Trial. , 2015, Sleep.

[15]  M. Preisig,et al.  Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. , 2015, The Lancet. Respiratory medicine.

[16]  B. Pliska,et al.  Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment. , 2014, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[17]  G. Hamilton,et al.  Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis. , 2014, Sleep medicine.

[18]  K. Strohl,et al.  Effect of upper-airway stimulation for obstructive sleep apnoea on airway dimensions , 2014, European Respiratory Journal.

[19]  L. Sharples,et al.  A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO) , 2014, Thorax.

[20]  K. Kim,et al.  Clinical Effect of Surgical Correction for Nasal Pathology on the Treatment of Obstructive Sleep Apnea Syndrome , 2014, PloS one.

[21]  Thomas G. Schell,et al.  Definition of an Effective Oral Appliance for the Treatment of Obstructive Sleep Apnea and Snoring: A Report of the American Academy of Dental Sleep Medicine , 2014 .

[22]  S. Tufik,et al.  Mandibular advancement device and CPAP upon cardiovascular parameters in OSA , 2014, Sleep and Breathing.

[23]  P. van de Heyning,et al.  Upper-airway stimulation for obstructive sleep apnea. , 2014, The New England journal of medicine.

[24]  A. El‐Solh,et al.  Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: An observational study , 2013, Respirology.

[25]  A. Malhotra,et al.  Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. , 2013, American journal of respiratory and critical care medicine.

[26]  A. Malhotra,et al.  A multicenter evaluation of oral pressure therapy for the treatment of obstructive sleep apnea. , 2013, Sleep medicine.

[27]  S. Tufik,et al.  Effect of speech therapy as adjunct treatment to continuous positive airway pressure on the quality of life of patients with obstructive sleep apnea. , 2013, Sleep medicine.

[28]  J. Stradling,et al.  The effects of Provent on moderate to severe obstructive sleep apnoea during continuous positive airway pressure therapy withdrawal: a randomised controlled trial , 2013, Thorax.

[29]  J. Maurer,et al.  Evaluation of drug-induced sleep endoscopy as a patient selection tool for implanted upper airway stimulation for obstructive sleep apnea. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[30]  T. Young,et al.  Increased prevalence of sleep-disordered breathing in adults. , 2013, American journal of epidemiology.

[31]  J. Fleetham,et al.  Mandibular advancement splint as short-term alternative treatment in patients with obstructive sleep apnea already effectively treated with continuous positive airway pressure. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[32]  G. Marks,et al.  Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. , 2013, American journal of respiratory and critical care medicine.

[33]  Xinzhe Shi,et al.  The Impact of Bariatric Surgery on Obstructive Sleep Apnea: A Systematic Review , 2013, Obesity Surgery.

[34]  B. Stegenga,et al.  Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on dental side effects , 2012, Clinical Oral Investigations.

[35]  D. Rapoport,et al.  Changes in lung volume and upper airway using MRI during application of nasal expiratory positive airway pressure in patients with sleep-disordered breathing. , 2011, Journal of applied physiology.

[36]  R. Berry,et al.  Long-term use of a nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[37]  A. Holley,et al.  Comparison of adjustable and fixed oral appliances for the treatment of obstructive sleep apnea. , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[38]  B. Stegenga,et al.  Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects , 2011, Clinical Oral Investigations.

[39]  R. Berry,et al.  A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. , 2011, Sleep.

[40]  D. Rapoport,et al.  Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea. , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[41]  F. Valera,et al.  Propofol-induced sleep: Polysomnographic evaluation of patients with obstructive sleep apnea and controls , 2010, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[42]  S. Tufik,et al.  Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. , 2009, Sleep medicine.

[43]  P. Abraham,et al.  Microvascular endothelial function in obstructive sleep apnea: Impact of continuous positive airway pressure and mandibular advancement. , 2009, Sleep medicine.

[44]  P. Genta,et al.  Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. , 2009, American journal of respiratory and critical care medicine.

[45]  N. Meslier,et al.  Mandibular Advancement for Obstructive Sleep Apnea: Dose Effect on Apnea, Long-Term Use and Tolerance , 2008, Respiration.

[46]  N. Collop,et al.  An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea. , 2008, Chest.

[47]  P. Cistulli,et al.  A follow-up study of dental and skeletal changes associated with mandibular advancement splint use in obstructive sleep apnea. , 2007, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[48]  P. Lavie,et al.  The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. , 2007, Chest.

[49]  Max Hirshkowitz,et al.  Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. , 2006, Sleep.

[50]  K. Ferguson,et al.  Oral appliances for snoring and obstructive sleep apnea: a review. , 2006, Sleep.

[51]  A. Lowe,et al.  Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: Part 1. Cephalometric analysis. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[52]  M. Marklund.  Predictors of long-term orthodontic side effects from mandibular advancement devices in patients with snoring and obstructive sleep apnea. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[53]  Mary Farbood,et al.  Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: Part 2. Study-model analysis. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[54]  M. Puhan,et al.  Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial , 2005, BMJ : British Medical Journal.

[55]  A. Malhotra,et al.  Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. , 2005, American journal of respiratory and critical care medicine.

[56]  R. Mcevoy,et al.  Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. , 2004, American journal of respiratory and critical care medicine.

[57]  B. Fleury,et al.  Mandibular advancement titration for obstructive sleep apnea: optimization of the procedure by combining clinical and oximetric parameters. , 2004, Chest.

[58]  K. Franklin,et al.  Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success. , 2004, Chest.

[59]  I. Ringqvist,et al.  A Prospective Randomized Study Comparing Two Different Degrees of Mandibular Advancement with a Dental Appliance in Treatment of Severe Obstructive Sleep Apnea , 2003, Sleep and Breathing.

[60]  H. Engleman,et al.  Improving CPAP use by patients with the sleep apnoea/hypopnoea syndrome (SAHS). , 2003, Sleep medicine reviews.

[61]  S. Tufik,et al.  Effects of mandibular posture on obstructive sleep apnea severity and the temporomandibular joint in patients fitted with an oral appliance. , 2002, Sleep.

[62]  K. Franklin,et al.  Orthodontic side-effects of mandibular advancement devices during treatment of snoring and sleep apnoea. , 2001, European journal of orthodontics.

[63]  H. Tanzawa,et al.  Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing. , 2000, Chest.

[64]  S. Kuna,et al.  An oral elastic mandibular advancement device for obstructive sleep apnea. , 2000, American journal of respiratory and critical care medicine.

[65]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[66]  M. Broudy,et al.  Increased severity of obstructive sleep apnea after bedtime alcohol ingestion: diagnostic potential and proposed mechanism of action. , 1982, Sleep.

[67]  F. Papay,et al.  Hypoglossal nerve stimulation in the treatment of obstructive sleep apnea : A systematic review and meta-analysis , 2016 .

[68]  C. Monasterio,et al.  Five years of sleep apnea treatment with a mandibular advancement device. Side effects and technical complications. , 2010, The Angle orthodontist.

[69]  D. White.  The pathogenesis of obstructive sleep apnea: advances in the past 100 years. , 2006, American journal of respiratory cell and molecular biology.