POINT: Should Hypopneas Only Be Scored When Accompanied By Oxygen Desaturation? Yes

Abstract

The apnea hypopnea index (AHI) is the primary metric used to determine the presence of sleep apnea. In most patients, hypopneas outnumber apneas, so hypopnea scoring affects the prevalence of OSA, the procedures required for its diagnosis, and the interpretation of pretest probability scores and outcome studies. In fact, this debate gets at a very fundamental question: “What is OSA?” What is a hypopnea? Grossly, it is a reduction in airflow during sleep, without complete cessation of breathing (which is referred to as an apnea). Existing hypopnea definitions require variable amounts of airflow reduction accompanied by either arousal from sleep or oxygen desaturation before an event can be “scored.” Historically, numerous definitions have been used (we counted 13 distinct ways for the identification of hypopneas in the 30 papers cited to support an American College of Physicians guideline on OSA management1Qaseem A. Holty J.E.C. Owens D.K. et al.Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians.Ann Intern Med. 2013; 159: 471-483PubMed Google Scholar), but variations in the resulting AHI across definitions are driven mainly by whether an arousal or an oxygen desaturation is required to score an event as a hypopnea.2Ruehland W. Rochford P.D. O’Donoghue F.J. et al.The new AASM criteria for scoring hypopneas: Impact on the apnea hypopnea index.Sleep. 2009; 32: 150-157Crossref PubMed Scopus (453) Google Scholar In 2007, a scoring manual published by the American Academy of Sleep Medicine (AASM) limited hypopnea scoring to three specific definitions. The most updated version of this manual endorses two definitions, one that allows for an event to be scored in the presence of an “arousal” from sleep (≥30% drop in surrogate measure for flow for 10 seconds accompanied by a 3% oxygen desaturation or an arousal) and another that mandates an oxygen desaturation (≥30% drop in surrogate measure for flow for 10 seconds accompanied by a 4% oxygen desaturation). Our position in this debate is that the oxygen desaturation requirement is more clinically relevant and reproducible and that dual diagnostic criteria for scoring events makes case-finding, epidemiologic investigation, and assessment of treatment outcomes unreliable. A review of OSA prevalence will illustrate the importance of the hypopnea definition. The most commonly cited US prevalence data come from the Wisconsin Sleep Cohort (WSC).3Young T. Palta M. Dempsey J. et al.The occurrence of sleep-disordered breathing among middle-aged adults.N Engl J Med. 1993; 328: 1230-1235Crossref PubMed Scopus (8230) Google Scholar,4Peppard P. Young T. Barnet J.H. Palta M. Hagen E.W. Hla K.M. Increased prevalence of sleep-disordered breathing in adults.Am J Epidemiol. 2013; 177: 1006-1014Crossref PubMed Scopus (2454) Google Scholar In this study, hypopneas were scored only when airflow reduction was accompanied by at least a 4% desaturation (arousals were not included). According to WSC data,4Peppard P. Young T. Barnet J.H. Palta M. Hagen E.W. Hla K.M. Increased prevalence of sleep-disordered breathing in adults.Am J Epidemiol. 2013; 177: 1006-1014Crossref PubMed Scopus (2454) Google Scholar the estimated prevalence of OSA for a 30- to 49- or 50- to 70-year-old US man of average weight (BMI, 25.0-29.9 kg/m2) is 18.3% and 36.6%, respectively. What is the prevalence of OSA in the United States when arousals are added to the hypopnea definition? To our knowledge, direct estimates are not available. However, multiple studies have shown that, when arousals are included in the definition, hypopneas will increase up to eight-fold, and OSA prevalence will increase two- to threefold when compared with the use of oxygen desaturation alone.2Ruehland W. Rochford P.D. O’Donoghue F.J. et al.The new AASM criteria for scoring hypopneas: Impact on the apnea hypopnea index.Sleep. 2009; 32: 150-157Crossref PubMed Scopus (453) Google Scholar,5BaHammam A. Obeidat A. Barataman K. et al.A comparison between the AASM 2012 and 2007 definitions for detecting hypopnea.Sleep Breath. 2014; 18: 767-773Crossref PubMed Scopus (55) Google Scholar,6Korotinsky A. Assefa S.Z. Diaz-Abad M. Wickwire E.M. Scharf S.M. Comparison of American Academy of Sleep Medicine (AASM) versus Center for Medicare and Medicaid Services (CMS) polysomnography (PSG) scoring rules on AHI and eligibility for continuous positive airway pressure (CPAP) treatment.Sleep Breath. 2016; 20: 1169-1174Crossref PubMed Scopus (12) Google Scholar If arousal-based scoring had been used in the WSC, the prevalence of OSA in average weight men aged 30 to 49 and 50 to 70 years old would be 36% to 55% and 73% to 100%, respectively. Data from other countries confirm the dramatic effect that arousal scoring has on prevalence. The HypnoLaus study randomly sampled a population from Switzerland and used modern respiratory sensors and arousal criteria to score hypopneas and estimate the AHI. They analyzed polysomnogram data from 2021 participants who had an average BMI of 25.6 ± 4.1 kg/m2. The authors found the average man aged 40 to 59 and ≥60 years old had a median AHI score of 11.7 (interquartile range, 6.1-21.1) and 21.1 (interquartile range, 9.4-35.6), respectively. In essence, when arousal criteria were used to score hypopneas, the average man ≥40 years old had OSA. In keeping with data cited earlier, these authors also found that the AHI dropped by a factor of 2.3 when a 4% desaturation criteria for hypopneas was applied.7Heinzer R. Vat S. Marques-Vidal P. et al.Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.Lancet Respir Med. 2015; 3: 310-318Abstract Full Text Full Text PDF PubMed Scopus (1240) Google Scholar It is clear that, when arousals are included in the hypopnea definition, OSA diagnoses increase dramatically, relative to the use of a 4% desaturation requirement. Overall disease prevalence exceeds 80% in a substantial portion of the average weight adult male population.7Heinzer R. Vat S. Marques-Vidal P. et al.Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.Lancet Respir Med. 2015; 3: 310-318Abstract Full Text Full Text PDF PubMed Scopus (1240) Google Scholar Given the resulting burden on patients and health resources, it is important to ensure that an arousal-based definition of the AHI identifies individuals who will benefit from a specific treatment. Although the increase in prevalence could be largely eliminated if the OSA diagnostic threshold were changed from an AHI of 5 to one of 15 when arousals are included, neither the AASM nor our colleagues on the opposite side of this debate advocate for shifting diagnostic criteria. The AASM made the case for arousal-based scoring in a recent position paper where they cited studies showing an association between arousals and sleepiness, fatigue, and neurocognitive outcomes.8Malhotra R. Kirsch D. Kristo D. et al.Polysomnography for obstructive sleep apnea should include arousal-based scoring: an American Academy of Sleep Medicine position statement.J Clin Sleep Med. 2018; 14: 1245-1247Crossref PubMed Scopus (53) Google Scholar While we do not dispute this association, past data have shown desaturations are also associated with symptoms, and are better correlated with cardiovascular outcomes.9Redline S. Kapur V.K. Sanders M.H. et al.Effects of varying approaches for identifying respiratory disturbances on sleep apnea assessment.Am J Respir Crit Care Med. 2000; 161: 369-374Crossref PubMed Scopus (180) Google Scholar, 10Punjabi N. Newman A.B. Young T.B. et al.Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas.Am J Respir Crit Care Med. 2008; 177: 1150-1155Crossref PubMed Scopus (209) Google Scholar, 11Mansukhani M. Kolla B.P. Wang Z. et al.Effect of varying definitions of hypopnea on the diagnosis and clinical outcomes of sleep disordered breathing: a systematic review and meta-analysis.J Clin Sleep Med. 2019; 15: 687-696Crossref PubMed Scopus (18) Google Scholar The position paper failed to mention that interobserver agreement when scoring arousals on polysomnograms is poor when compared with oxygen desaturation events.12Whitney C. Gottlieb D.J. Redline S. et al.Reliability of scoring respiratory disturbance indices and sleep staging.Sleep. 1998; 21: 749-757Crossref PubMed Scopus (262) Google Scholar With arousal-based scoring of hypopneas, a patient can have OSA in one laboratory but not another because of interscorer variability. Other expert panels have recognized this problem and recommended against the inclusion of arousals in scoring until greater interscorer reliability has been achieved.13Mann E. Nandkumar S. Addy N. et al.Study design considerations for sleep-disordered breathing devices.J Clin Sleep Med. 2020; 16: 441-449Crossref PubMed Google Scholar More importantly, the position paper cited only two studies to support the contention that arousal-based scoring identifies patients who benefit from treatment. Both were observational, neither had a control group, and combined they included only 50 patients.14Guilleminault C. Hagen C.C. Huynh N.T. Comparison of hypopnea definitions in lean patients with known obstructive sleep apnea hypopnea syndrome (OSAHS).Sleep Breath. 2009; 13: 341-347Crossref PubMed Scopus (53) Google Scholar,15Guilleminault C. Stoohs R. Clerk A. Cetel M. Maistros P. A cause of excessive daytime sleepiness: the upper airway resistance syndrome.Chest. 1993; 104: 781-787Abstract Full Text Full Text PDF PubMed Scopus (838) Google Scholar One was retrospective and preselected only patients who had already benefited from therapy14Guilleminault C. Hagen C.C. Huynh N.T. Comparison of hypopnea definitions in lean patients with known obstructive sleep apnea hypopnea syndrome (OSAHS).Sleep Breath. 2009; 13: 341-347Crossref PubMed Scopus (53) Google Scholar; the other included patients with extensive, nonroutine prescreening.15Guilleminault C. Stoohs R. Clerk A. Cetel M. Maistros P. A cause of excessive daytime sleepiness: the upper airway resistance syndrome.Chest. 1993; 104: 781-787Abstract Full Text Full Text PDF PubMed Scopus (838) Google Scholar Although space (and restrictions on references) precludes citing them all here, the studies that show benefits with the use of definitive outcomes like mortality rates and cardiovascular disease are much larger and have used desaturation alone to identify hypopneas.10Punjabi N. Newman A.B. Young T.B. et al.Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas.Am J Respir Crit Care Med. 2008; 177: 1150-1155Crossref PubMed Scopus (209) Google Scholar,16Marti S. Sampol G. Munoz X. et al.Mortality in severe sleep apnoea/hypopnoea syndrome patients: impact of treatment.Eur Respir J. 2002; 20: 1511-1518Crossref PubMed Scopus (204) Google Scholar, 17Campos-Rodriguez F. Pena-Grinan N. Reyes-Nuñez N. et al.Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure.Chest. 2005; 128: 624-633Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 18Marin J. Carrizo S.J. Vicente E. Agusti A.G.N. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study.Lancet. 2005; 365: 1046-1053Abstract Full Text Full Text PDF PubMed Scopus (2688) Google Scholar The position paper recommends that, because arousals are associated with daytime symptoms, they should be included in the definition of a hypopnea. They must be treated because patients might benefit. Although the latter may be true, no prospective, controlled data support this contention. We should exclude arousals from hypopnea scoring in clinical practice until we have well-conducted trials that show that patients who are diagnosed with the use of this metric benefit from treatment. To do otherwise risks improper allocation of limited resources. Studies cited earlier prove that the inclusion of arousal criteria in the hypopnea definition will increase dramatically the AHI and OSA prevalence.2Ruehland W. Rochford P.D. O’Donoghue F.J. et al.The new AASM criteria for scoring hypopneas: Impact on the apnea hypopnea index.Sleep. 2009; 32: 150-157Crossref PubMed Scopus (453) Google Scholar,5BaHammam A. Obeidat A. Barataman K. et al.A comparison between the AASM 2012 and 2007 definitions for detecting hypopnea.Sleep Breath. 2014; 18: 767-773Crossref PubMed Scopus (55) Google Scholar,6Korotinsky A. Assefa S.Z. Diaz-Abad M. Wickwire E.M. Scharf S.M. Comparison of American Academy of Sleep Medicine (AASM) versus Center for Medicare and Medicaid Services (CMS) polysomnography (PSG) scoring rules on AHI and eligibility for continuous positive airway pressure (CPAP) treatment.Sleep Breath. 2016; 20: 1169-1174Crossref PubMed Scopus (12) Google Scholar,11Mansukhani M. Kolla B.P. Wang Z. et al.Effect of varying definitions of hypopnea on the diagnosis and clinical outcomes of sleep disordered breathing: a systematic review and meta-analysis.J Clin Sleep Med. 2019; 15: 687-696Crossref PubMed Scopus (18) Google Scholar Patients labeled with OSA by arousal criteria, but missed by desaturations alone, are younger and thinner with mild OSA. When we eliminate arousals from the hypopnea definition, it is largely these patients whom we lose. The relationship between mild OSA and outcomes is tentative at best,19Chowdhuri S. Quan S.F. Almeida F. et al.An official American Thoracic Society research statement: impact of mild obstructive sleep apnea in adults.Am J Respir Crit Care Med. 2016; 193: e37-e54Crossref PubMed Scopus (88) Google Scholar and meta-analyses20Marshall N. Barnes M. Travier N. et al.Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta-analysis.Thorax. 2006; 61: 430-434Crossref PubMed Scopus (154) Google Scholar and randomized trials21Weaver T. Mancini C. Maislin G. et al.Continuous positive airway pressure treament of sleepy patients with milder obstructive sleep apnea.Am J Respir Crit Care Med. 2012; 186: 677-683Crossref PubMed Scopus (150) Google Scholar,22Kushida C. Nichols D.A. Holmes T.H. et al.Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the apnea positive pressure long-term efficacy study (APPLES).Sleep. 2012; 35: 1593-1602Crossref PubMed Scopus (246) Google Scholar have failed to prove that clinically important improvements result from treatment of mild OSA with positive airway pressure. Mild OSA trials that have come close to showing benefit have used desaturation criteria to score hypopneas,21Weaver T. Mancini C. Maislin G. et al.Continuous positive airway pressure treament of sleepy patients with milder obstructive sleep apnea.Am J Respir Crit Care Med. 2012; 186: 677-683Crossref PubMed Scopus (150) Google Scholar,22Kushida C. Nichols D.A. Holmes T.H. et al.Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the apnea positive pressure long-term efficacy study (APPLES).Sleep. 2012; 35: 1593-1602Crossref PubMed Scopus (246) Google Scholar with the exception of the MERGE trial that estimated arousals with the use of respiratory changes from a modified portable sleep apnea testing (type) III device.23Wimms A. Kelly J.L. Turnbull C.D. et al.Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial.Lancet Respir Med. 2020; 8: 349-358Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar To summarize, there are few data to indicate that leaving mild OSA (identified with arousal-based scoring) undiagnosed equates to missing treatable disease. With different hypopnea definitions, the AHI loses meaning, and OSA remains a nebulous diagnosis. We can choose the less reproducible definition that is weakly correlated with treatment response and makes the average 50-year-old man have OSA, or we can stick with desaturation criteria alone and know that, when we prescribe positive airway pressure, we are improving outcomes. Eliminating arousals poses no public health risk; on the contrary, it would allow us to dedicate more resources where they are urgently needed. That constitutes a net benefit to public health.