Supine position related obstructive sleep apnea in adults: pathogenesis and treatment.

The most striking feature of obstructive respiratory events is that they are at their most severe and frequent in the supine sleeping position: indeed, more than half of all obstructive sleep apnea (OSA) patients can be classified as supine related OSA. Existing evidence points to supine related OSA being attributable to unfavorable airway geometry, reduced lung volume, and an inability of airway dilator muscles to adequately compensate as the airway collapses. The role of arousal threshold and ventilatory control instability in the supine position has however yet to be defined. Crucially, few physiological studies have examined patients in the lateral and supine positions, so there is little information to elucidate how breathing stability is affected by sleep posture. The mechanisms of supine related OSA can be overcome by the use of continuous positive airway pressure. There are conflicting data on the utility of oral appliances, while the effectiveness of weight loss and nasal expiratory resistance remains unclear. Avoidance of the supine posture is efficacious, but long term compliance data and well powered randomized controlled trials are lacking. The treatment of supine related OSA remains largely ignored in major clinical guidelines. Supine OSA is the dominant phenotype of the OSA syndrome. This review explains why the supine position so favors upper airway collapse and presents the available data on the management of patients with supine related OSA.

[1]  Doo Hee Han,et al.  The implication of sleep position in the evaluation of surgical outcomes in obstructive sleep apnea , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[2]  Abnormalities in the flow-volume loop in obstructive sleep apnoea sitting and supine. , 1984, Thorax.

[3]  D. Pevernagie,et al.  Relations between sleep stage, posture and effective nasal CPAP levels in OSA. , 1992, Sleep.

[4]  J. Fleetham,et al.  A cephalometric and electromyographic study of upper airway structures in the upright and supine positions. , 1994, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[5]  T. Nishino,et al.  Influences of head positions and bite opening on collapsibility of the passive pharynx. , 2004, Journal of applied physiology.

[6]  J. Fleetham,et al.  Mandibular posture during sleep in healthy adults. , 1998, Archives of oral biology.

[7]  Ron Kikinis,et al.  Anatomic and physiologic predictors of apnea severity in morbidly obese subjects. , 2003, Sleep.

[8]  A. Oksenberg,et al.  Positional Therapy for Obstructive Sleep Apnea Patients: A 6‐Month Follow‐Up Study , 2006, The Laryngoscope.

[9]  Å. Tegelberg,et al.  Effects of a Mandibular Protruding Device on the Sleep of Patients with Obstructive Sleep Apnea and Snoring Problems: A 2-Year Follow-Up , 2003, Sleep and Breathing.

[10]  A. Woodcock,et al.  Do oral appliances enlarge the airway in patients with obstructive sleep apnoea? A prospective computerized tomographic study. , 2000, European journal of orthodontics.

[11]  A. Sovijärvi,et al.  Determination of functional residual capacity with 133-xenon radiospirometry. Comparison with body plethysmography and helium spirometry. Effect of body position. , 1980, Scandinavian journal of clinical and laboratory investigation.

[12]  T Penzel,et al.  Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea. , 2001, Sleep.

[13]  A. Malhotra,et al.  The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep. , 2003, Sleep.

[14]  F. Sériès,et al.  Importance of sleep stage- and body position-dependence of sleep apnoea in determining benefits to auto-CPAP therapy. , 2001, The European respiratory journal.

[15]  S. Ancoli-Israel,et al.  Comparing Night-to-Night Variability of Sleep Measures in Elderly African Americans and Whites , 2005, Behavioral sleep medicine.

[16]  S. Kurata,et al.  Mouth-opening Increases Upper-airway Collapsibility without Changing Resistance during Midazolam Sedation , 2004, Journal of dental research.

[17]  N. Pride,et al.  Postural changes in lung volumes and respiratory resistance in subjects with obesity. , 2005, Journal of applied physiology.

[18]  K. Lam,et al.  Obstructive sleep apnea is independently associated with insulin resistance. , 2002, American journal of respiratory and critical care medicine.

[19]  D. White,et al.  Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). , 1992, The Journal of clinical investigation.

[20]  T. Ono,et al.  Effect of changes in the breathing mode and body position on tongue pressure with respiratory-related oscillations. , 1999, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[21]  Daniel J Buysse,et al.  Sources of variability in epidemiological studies of sleep using repeated nights of in-home polysomnography: SWAN Sleep Study. , 2012, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[22]  D. Hillman,et al.  Influence of head extension, flexion, and rotation on collapsibility of the passive upper airway. , 2008, Sleep.

[23]  M. Goldsworthy,et al.  Poor long-term patient compliance with the tennis ball technique for treating positional obstructive sleep apnea. , 2009, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[24]  P. Sheedy,et al.  Effects of body position on the upper airway of patients with obstructive sleep apnea. , 1995, American journal of respiratory and critical care medicine.

[25]  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.

[26]  A. Campbell,et al.  Mandibular advancement splint improves indices of obstructive sleep apnoea and snoring but side effects are common. , 2002, The New Zealand medical journal.

[27]  M. Younes,et al.  Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. , 2003, American journal of respiratory and critical care medicine.

[28]  J. Mercer,et al.  Accurate position monitoring and improved supine-dependent obstructive sleep apnea with a new position recording and supine avoidance device. , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[29]  Analysis of pharyngeal resistance and genioglossal EMG activity using a model of orifice flow. , 1992, Journal of applied physiology.

[30]  P. L. Smith,et al.  Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure. , 1988, Journal of applied physiology.

[31]  T. Ono,et al.  Respiratory-related genioglossus electromyographic activity in response to head rotation and changes in body position. , 2000, The Angle orthodontist.

[32]  D. Sampson,et al.  Effect of body posture on pharyngeal shape and size in adults with and without obstructive sleep apnea. , 2008, Sleep.

[33]  S. Cass,et al.  Use of electrical vestibular stimulation to alter genioglossal muscle activity in awake cats. , 2003, Journal of vestibular research : equilibrium & orientation.

[34]  P. L. Smith,et al.  Weight loss in mildly to moderately obese patients with obstructive sleep apnea. , 1985, Annals of internal medicine.

[35]  A. Malhotra,et al.  Ventilatory control and airway anatomy in obstructive sleep apnea. , 2004, American journal of respiratory and critical care medicine.

[36]  David D. Sampson,et al.  Measurement, Reconstruction, and Flow-Field Computation of the Human Pharynx With Application to Sleep Apnea , 2010, IEEE Transactions on Biomedical Engineering.

[37]  Yoo-Sam Chung,et al.  The Effect of Uvula-Preserving Palatopharyngoplasty in Obstructive Sleep Apnea on Globus Sense and Positional Dependency , 2010, Clinical and experimental otorhinolaryngology.

[38]  J. Fleetham,et al.  Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx , 1999, Thorax.

[39]  A. Oksenberg,et al.  Positional vs Nonpositional Obstructive Sleep Apnea Patients* Anthropomorphic, Nocturnal Polysomnographic, and Multiple Sleep Latency Test Data , 1997 .

[40]  F. J. Nieto,et al.  Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. , 1999, American journal of respiratory and critical care medicine.

[41]  K. Franklin,et al.  Treatment success with a mandibular advancement device is related to supine-dependent sleep apnea. , 1998, Chest.

[42]  John Trinder,et al.  The effect of sleep onset on upper airway muscle activity in patients with sleep apnoea versus controls , 2005, The Journal of physiology.

[43]  D. Bettinelli,et al.  Effect of gravity and posture on lung mechanics. , 2002, Journal of applied physiology.

[44]  J Basterra,et al.  Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects. , 2001, The European respiratory journal.

[45]  H. Tinteren,et al.  The role of sleep position in obstructive sleep apnea syndrome , 2006, European Archives of Oto-Rhino-Laryngology and Head & Neck.

[46]  N. Pride,et al.  Effects of posture on respiratory mechanics in obesity. , 1995, Journal of applied physiology.

[47]  Reyes Enciso,et al.  Patients with positional versus nonpositional obstructive sleep apnea: a retrospective study of risk factors associated with apnea-hypopnea severity. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[48]  Jung Hwa Hong,et al.  Determining optimal sleep position in patients with positional sleep‐disordered breathing using response surface analysis , 2009, Journal of sleep research.

[49]  T. Desudchit,et al.  Clinical and polysomnographic data of positional sleep apnea and its predictors , 2012, Sleep and Breathing.

[50]  M. Partinen,et al.  A cognitive-behavioral weight reduction program in the treatment of obstructive sleep apnea syndrome with or without initial nasal CPAP: a randomized study. , 2004, Sleep medicine.

[51]  M. Metersky,et al.  The effect of polysomnography on sleep position: possible implications on the diagnosis of positional obstructive sleep apnea. , 1996, Respiration; international review of thoracic diseases.

[52]  J. Fleetham,et al.  Associations among upper airway structure, body position, and obesity in skeletal Class I male patients with obstructive sleep apnea. , 1996, 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]  A. Chesson,et al.  The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications , 2007 .

[54]  P. L. Smith,et al.  Effect of tracheal and tongue displacement on upper airway airflow dynamics. , 1996, Journal of applied physiology.

[55]  J. Tuomilehto,et al.  Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea. , 2009, American journal of respiratory and critical care medicine.

[56]  A. Oksenberg,et al.  Association of body position with severity of apneic events in patients with severe nonpositional obstructive sleep apnea. , 2000, Chest.

[57]  A. Oksenberg,et al.  The sleep supine position has a major effect on optimal nasal continuous positive airway pressure : relationship with rapid eye movements and non-rapid eye movements sleep, body mass index, respiratory disturbance index, and age. , 1999, Chest.

[58]  A. Broström,et al.  Positional sensitivity as a confounder in diagnosis of severity of obstructive sleep apnea , 2013, Sleep and Breathing.

[59]  C F Ryan,et al.  Mechanical properties of the velopharynx in obese patients with obstructive sleep apnea. , 1996, American journal of respiratory and critical care medicine.

[60]  T. Seto,et al.  The effect of posture on Cheyne-Stokes respirations and hemodynamics in patients with heart failure. , 2009, Sleep.

[61]  P. L. Smith,et al.  Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. , 1991, The American review of respiratory disease.

[62]  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.

[63]  P. Pelosi,et al.  Respiratory system mechanics in sedated, paralyzed, morbidly obese patients. , 1997, Journal of applied physiology.

[64]  Radha M. Parikh,et al.  Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure. , 2007, Sleep.

[65]  S. Sands,et al.  Phenotypes of patients with mild to moderate obstructive sleep apnoea as confirmed by cluster analysis , 2012, Respirology.

[66]  A. Malhotra,et al.  Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea , 2006, Thorax.

[67]  J. Remmers,et al.  Lung volume and collapsibility of the passive pharynx in patients with sleep-disordered breathing. , 2007, Journal of applied physiology.

[68]  G. Clark,et al.  Treatment outcomes of mandibular advancement devices in positional and nonpositional OSA patients. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[69]  D. Hudgel,et al.  A long-term randomized, cross-over comparison of auto-titrating and standard nasal continuous airway pressure. , 2000, Sleep.

[70]  M. Naughton,et al.  Lateral sleeping position reduces severity of central sleep apnea / Cheyne-Stokes respiration. , 2006, Sleep.

[71]  Kamel Rekab,et al.  Sleep Apnea Avoidance Pillow Effects on Obstructive Sleep Apnea Syndrome and Snoring , 2004, Sleep and Breathing.

[72]  N. de Vries,et al.  Quantitative effects of trunk and head position on the apnea hypopnea index in obstructive sleep apnea. , 2011, Sleep.

[73]  D. Hillman,et al.  Variability of human upper airway collapsibility during sleep and the influence of body posture and sleep stage , 2011, Journal of sleep research.

[74]  Bonnie K. Lind,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study , 2000 .

[75]  N. Douglas,et al.  Effect of posture on upper airway dimensions in normal human. , 1994, American journal of respiratory and critical care medicine.

[76]  P. Tanskanen,et al.  The effect of patient positioning on dynamic lung compliance , 1997, Acta anaesthesiologica Scandinavica.

[77]  D. Navajas,et al.  Effect of body posture on respiratory impedance. , 1988, Journal of applied physiology.

[78]  M. Skinner,et al.  Efficacy of the ‘tennis ball technique’ versus nCPAP in the management of position‐dependent obstructive sleep apnoea syndrome , 2008, Respirology.

[79]  Sabin R. Bista,et al.  Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults. , 2010, Sleep.

[80]  A. Malhotra,et al.  Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. , 2011, Clinical science.

[81]  H. Nakano,et al.  Effects of body position on snoring in apneic and nonapneic snorers. , 2003, Sleep.

[82]  T. Ono,et al.  Effects of Head and Body Position on Two- and Three-dimensional Configurations of the Upper Airway , 2000, Journal of dental research.

[83]  S. Tsuiki,et al.  Effects of mandibular advancement on airway curvature and obstructive sleep apnoea severity , 2004, European Respiratory Journal.

[84]  N. Zamel,et al.  Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea. , 1986, The New England journal of medicine.

[85]  R. Maestri,et al.  Night-to-night repeatability of measurements of nocturnal breathing disorders in clinically stable chronic heart failure patients , 2011, Sleep and Breathing.

[86]  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.

[87]  P. Hanly,et al.  Gender differences in the polysomnographic features of obstructive sleep apnea. , 2000, American journal of respiratory and critical care medicine.

[88]  T. Ono,et al.  Effects of a titratable oral appliance on supine airway size in awake non-apneic individuals. , 2001, Sleep.

[89]  T. Young,et al.  Prospective study of the association between sleep-disordered breathing and hypertension. , 2000, The New England journal of medicine.

[90]  Richard L. Jones,et al.  The effects of body mass index on lung volumes. , 2006, Chest.

[91]  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.

[92]  D. Suchecki,et al.  The variability of the apnoea–hypopnoea index , 2001, Journal of sleep research.

[93]  M. Crossley,et al.  Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome. , 1999, Chest.

[94]  B. Edwards,et al.  A method for measuring and modeling the physiological traits causing obstructive sleep apnea. , 2011, Journal of applied physiology.

[95]  Elisabeth Hultcrantz,et al.  Positioner–a method for preventing sleep apnea , 2007, Acta oto-laryngologica.

[96]  J. Kirkness,et al.  Effect of end-expiratory lung volume on upper airway collapsibility in sleeping men and women. , 2010, Journal of applied physiology.

[97]  W. B. Van de Graaff,et al.  Thoracic influence on upper airway patency , 1988 .

[98]  A I Pack,et al.  Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. , 1995, American journal of respiratory and critical care medicine.

[99]  Raanan Arens,et al.  Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. , 2003, American journal of respiratory and critical care medicine.

[100]  Carl J Stepnowsky,et al.  Nightly Variability of Sleep-Disordered Breathing Measured over 3 Nights , 2004, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[101]  J. Hartikainen,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. , 1998, Clinical physiology.

[102]  T. Ono,et al.  Mandibular advancement modulates respiratory-related genioglossus electromyographic activity , 2009, Sleep and Breathing.

[103]  G. Drummond,et al.  Effect of posture and breathing route on genioglossal electromyogram activity in normal subjects and in patients with the sleep apnea/hypopnea syndrome. , 1993, The American review of respiratory disease.

[104]  Chae-Seo Rhee,et al.  Positional dependency in Asian patients with obstructive sleep apnea and its implication for hypertension. , 2011, Archives of otolaryngology--head & neck surgery.

[105]  Y. Itasaka,et al.  Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea:Analysis by sleep position , 1998, Psychiatry and clinical neurosciences.

[106]  T. Nishino,et al.  Lateral Position Decreases Collapsibility of the Passive Pharynx in Patients with Obstructive Sleep Apnea , 2002, Anesthesiology.

[107]  N. Gadoth,et al.  Obstructive sleep apnoea in adults: body postures and weight changes interactions , 2012, Journal of sleep research.

[108]  J B West,et al.  Microgravity reduces sleep-disordered breathing in humans. , 2001, American journal of respiratory and critical care medicine.

[109]  A. Oksenberg,et al.  Avoiding the supine position during sleep lowers 24 h blood pressure in obstructive sleep apnea (OSA) patients , 1997, Journal of Human Hypertension.

[110]  J. Wheatley,et al.  Onset of airflow limitation in a collapsible tube model: impact of surrounding pressure, longitudinal strain, and wall folding geometry. , 2010, Journal of applied physiology.

[111]  P. Catcheside,et al.  Abdominal compression increases upper airway collapsibility during sleep in obese male obstructive sleep apnea patients. , 2009, Sleep.

[112]  J. Gaughan,et al.  Comparison of positional therapy to CPAP in patients with positional obstructive sleep apnea. , 2010, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[113]  A. Oksenberg,et al.  REM-related obstructive sleep apnea: the effect of body position. , 2010, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[114]  A I Pack,et al.  Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. , 1993, The American review of respiratory disease.

[115]  N. de Vries,et al.  The undervalued potential of positional therapy in position-dependent snoring and obstructive sleep apnea—a review of the literature , 2012, Sleep and Breathing.

[116]  P. L. Smith,et al.  Abbreviated method for assessing upper airway function in obstructive sleep apnea. , 2000, Chest.

[117]  B. Gersh,et al.  Obstructive sleep apnea: implications for cardiac and vascular disease. , 2003, JAMA.

[118]  Masaaki Suzuki,et al.  Three-dimensional Morphological Analyses of Positional Dependence in Patients with Obstructive Sleep Apnea Syndrome , 2009, Anesthesiology.

[119]  P. Calverley,et al.  Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. , 2004, European heart journal.

[120]  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.

[121]  D. White,et al.  The influence of increasing ventilatory effort on arousal from sleep. , 1990, The American review of respiratory disease.

[122]  P Gagnon,et al.  Sleep positions and position shifts in five age groups: an ontogenetic picture. , 1992, Sleep.

[123]  E. Svanborg,et al.  Cheyne-Stokes respiration and supine dependency , 2005, European Respiratory Journal.

[124]  C. Mackenzie,et al.  Lung, chest wall, and total respiratory system resistances and elastances in the normal range of breathing. , 1992, The American review of respiratory disease.

[125]  P. Behrakis,et al.  Lung mechanics in sitting and horizontal body positions. , 1983, Chest.

[126]  N. Douglas,et al.  The effect of posture on airway caliber with the sleep-apnea/hypopnea syndrome. , 1995, American journal of respiratory and critical care medicine.

[127]  A. Harf,et al.  Constant vs. automatic continuous positive airway pressure therapy: home evaluation. , 2000, Chest.

[128]  R. Cartwright,et al.  Effect of sleep position on sleep apnea severity. , 1984, Sleep.

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

[130]  Terry Young,et al.  Longitudinal association of sleep-related breathing disorder and depression. , 2006, Archives of internal medicine.

[131]  F. Sériès,et al.  Changes in upper airway resistance with lung inflation and positive airway pressure. , 1990, Journal of applied physiology.

[132]  M Brandon Westover,et al.  The impact of body posture and sleep stages on sleep apnea severity in adults. , 2012, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[133]  B. Grant,et al.  Prevalence of positional sleep apnea in patients undergoing polysomnography. , 2005, Chest.

[134]  O. Mairesse,et al.  Body position and breathing abnormalities during sleep: a systematic study. , 2011, Pneumologia.

[135]  Yu-Lun Lo,et al.  Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. , 2009, Sleep.

[136]  Kazuya Yoshida,et al.  Influence of sleep posture on response to oral appliance therapy for sleep apnea syndrome. , 2001, Sleep.

[137]  M. Naughton,et al.  Comparison of supine-only and REM-only obstructive sleep apnoea. , 2012, Sleep medicine.

[138]  T. Young,et al.  Epidemiology of obstructive sleep apnea: a population health perspective. , 2002, American journal of respiratory and critical care medicine.

[139]  C F Mackenzie,et al.  Effect of Posture on Lung and Regional Chest Wall Mechanics , 1993, Anesthesiology.

[140]  A. Oksenberg,et al.  The effect of body posture on sleep-related breathing disorders: facts and therapeutic implications. , 1998, Sleep medicine reviews.

[141]  A. Malhotra,et al.  Postural effects on pharyngeal protective reflex mechanisms. , 2004, Sleep.

[142]  C. Tantucci,et al.  Expiratory flow limitation and orthopnea in massively obese subjects. , 2001, Chest.