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Editorials: Point and Counterpoint |

POINT: Is the Apnea-Hypopnea Index the Best Way to Quantify the Severity of Sleep-Disordered Breathing? Yes FREE TO VIEW

David M. Rapoport, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: D. M. R. receives patent royalties through New York University from Fisher & Paykel Healthcare Limited and Sefam Medical, Ltd for CPAP modifications; consulting fees and grant support from Fisher & Paykel Healthcare Limited; and consulting fees from BioMarin Pharmaceutical Inc, Morphy, Inc, and Jazz Pharmaceuticals plc.

CORRESPONDENCE TO: David M. Rapoport, MD, FCCP, Sleep Disorders Center, Bellevue Hospital, 462 First Ave, Room 7N2, New York, NY 10016


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(1):14-16. doi:10.1378/chest.15-1319
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Published online

Over the past 30 years, we have come to appreciate that during sleep there is a spectrum of obstructive breathing physiology ranging from mild snoring to severe OSA syndrome. By some estimates, significant abnormalities of breathing during sleep may affect as much as 15% to 20% of the adult population and 5% to 10% of children. The obesity epidemic makes it likely that these numbers will increase.

Although describing single periods of obstruction to normal breathing (an event) seems simple, we are still struggling to understand the clinical significance of repetitive obstructions (ie, the sleep apnea-hypopnea syndrome). At one extreme, we now know that during sleep, normal individuals experience a small number of partial (hypopnea) or even complete (apnea) respiratory obstructions that may have little or no health implications., At the other extreme, some severely affected individuals have virtually continuous 20- to 60-s cycles of obstruction during sleep and resumptions of breathing occurring up to 100 times/h. Almost all these latter individuals suffer severe psychophysiologic, neurologic, cardiovascular,,, and other consequences that justify calling this a disease, and these consequences appear to be markedly improved if the number of cycles (the apnea-hypopnea index [AHI]) is reduced by effective treatment.,

Until now, we have used the AHI to measure where an individual lies on the spectrum of their respiratory findings and of the syndrome. The AHI is a count of the number of complete and partial obstructions that occur per hour of sleep, but many definitions have been proposed that may account for some of the variability in assessing its value. In some definitions, only events with an associated oxygen desaturation are counted. Other definitions count all events that produce a physiologic response; thus, in addition to oxygen desaturation, arousal on EEG, surrogates of arousal, changes in sympathetic activity like pulse, and so forth are used to validate a detected respiratory event and allow it to contribute to the AHI. However, all definitions of AHI to date share the concept of defining severity of the syndrome by the occurrence rate of individual events deemed nonartifactual and significant (ie, the event itself has a detectable consequence). Because only the rate of events is captured, AHI incorporates severity of the individual events only to the extent that event severity correlates with frequency. There are other potentially independent axes of event severity (eg, the depth and duration of desaturation, the extent and duration of arousal, the level of sympathetic activation) that could affect severity of the overall clinical syndrome, but to date, there is no consensus and only limited research into their utility. Thus, most publications accept the AHI as the best available tool so far.

Two questions need to be asked about how well the AHI quantitates severity. The first is whether the current approach of using the rate of obstructive events (the AHI) to define the presence of disease is justified. Separately, one can ask how well the AHI measures disease severity.

To diagnose disease using a continuous metric implies a model whereby there is a bimodal distribution of the metric where disease can be more or less separated from normal by a threshold value. As pointed out previously, data in large populations show that the AHI is rarely 0, even in normal individuals. The association of sufficiently elevated AHI with negative outcomes confirms that some intensity of the sleep-disordered breathing event rate is abnormal. However, technology has led us to refine what events are being counted; thus, little attention has been paid to changing this threshold value. It seems intuitive that the threshold of disease should change as we refine what is counted, but the values of 5 and 15 events/h have been stubbornly present as cut points above which we say sleep apnea syndrome is present. This has led to many of the objections to the value of the AHI (for diagnosis). If the AHI comprises only complete or severe (eg, desaturating) individual obstructions, perhaps a low value can provide a sufficiently specific indicator of disease. In contrast, if all subtle events that produce at least a minimal physiologic consequence in the EEG or sympathetic nervous system are included, a somewhat higher value may increase sensitivity without too much loss of specificity. However, testing and refining these thresholds in clinical samples has been complicated by the extreme nonspecificity of the outcome measures used to define the “gold standard” of significant sleep apnea. Defining an epidemiologically healthy population is critical to deciding on a threshold value for disease, and this varies with the outcome being evaluated (eg, sleepiness, hypertension). Several studies have suggested that the threshold AHI number of events for disease is not low. For example, the Sleep Heart Health Study showed a median AHI, by an inclusive definition, of nearly 30/h in a large nonclinic population, and in the São Paulo cohort, it was reported that even in those with an AHI < 5/h and no daytime symptoms, evidence of upper-airway collapsibility during sleep (flow limitation) was very prominent (the 95 percentile cutoff of flow limitation was 30% of the time asleep). To reconcile these observations, I would argue that the AHI is useful at its extreme values but less so in the midrange. Despite evidence of widespread occurrence of obstructive events in the sleep of otherwise normal subjects, little doubt exists that in individuals with a very-low AHI (by any definition) compared with those with an elevated number (generally > 30/h), excessive sleepiness, hypertension, and other cardiovascular consequences are more frequent in the latter. Furthermore, many studies show improvement in clinical symptoms if the AHI is reduced by treatment in symptomatic subjects, again attesting to the ability of an elevated AHI to define disease. However, rather than trying to find an exact cutoff between normal and diseased, many of the same studies can be reinterpreted as showing that an intermediate AHI (ie, between 5 and 30/h, with some consideration of which AHI) confers no diagnosis but rather a rising probability of disease defined by clinical outcomes. This reasoning is different from but may underlie the common practice of diagnosing sleep apnea based on the AHI alone if > 15/h but requiring symptomatic consequences if between 5 and 15/h. The situation is similar to the use of an elevated BP taken in the clinic to define hypertension. The cutoff for hypertension was initially defined using measurements of BP norms in large, defined, nonclinic populations. These values were validated when it was shown that hypertension (ie, an elevated BP measurement) had consequences for health. We now use intermediate BPs in a different way in individuals with other risk factors (eg, diabetes, age) than in those who appear healthy. In a similar way, a high AHI is clearly a marker of disease. Thus, I conclude that AHI is a useful metric in defining the presence of OSA if severely elevated, and useful to define the risk of OSA if moderately increased.

This approach does not address the second question posed: Does the AHI measure severity of the disease once diagnosed? As the AHI increases, the probability of most sequelae increases, but a poor relationship exists between the frequency of respiratory events and severity of the symptoms or findings. Multiple studies have shown that the correlation between AHI and sleepiness (either subjectively or objectively measured by various tests) is poor if one looks only at those with OSA. This is also true when the relationship of AHI to hypertension is examined; there seems to be a plateau of increased risk of hypertension above a threshold AHI of 5 to 15/h, with little further increase at a higher AHI. Additionally, few data so far suggest that severity of hypertension tracks with the AHI. These observations are all compatible with the increasingly popular concept of differential susceptibility, that is, rather than just depending on the severity implied by physiologic challenge represented by the AHI, the individual’s genetic and environmental circumstances determine how much sleepiness, cardiovascular, or other consequence will occur for a given challenge.

In summary, the AHI is a useful metric in that it defines OSA; it is limited in that it does not measure severity well. Unfortunately, to date it remains the best, and certainly the most used, metric for severity. Perhaps this is because a low AHI defines normal, and a high AHI defines severely affected, leaving the possibly susceptible in a separate group. As a metric, AHI is the polar opposite of tools like respiratory flow rate (FEV1) as used in evaluating COPD in that FEV1 does not define the presence of COPD (many other diseases [eg, kyphoscoliosis, interstitial fibrosis] reduce flow rates by reducing lung volume). However, if limited to patients with COPD, FEV1 is quite good at measuring the severity of symptoms and the outcomes of the syndrome and operative mortality.

Until we finally understand the causes and mechanisms of differential susceptibility to sleep-related repetitive airway obstructions and arousals, the AHI continues to be the best we can do to evaluate patients with OSA for diagnosis. We can use it to assess their susceptibility to long-term consequences and to judge their response to therapy. However, it remains a poor assessment for the continuum of severity if by this we mean the severity of the other sequelae that are part of the syndrome. Finally, AHI remains an indispensable tool to probing the science of differential susceptibility; so far at least, AHI is the best way to describe the physical stimulus that must be related to the response in the susceptibility equation.

References

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine task force. Sleep. 1999;22:667-689 [PubMed]journal. [PubMed]
 
Peppard P.E. .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;177:1006-1014 [PubMed]journal. [CrossRef] [PubMed]
 
Goodwin J.L. .Vasquez M.M. .Silva G.E. .Quan S.F. . Incidence and remission of sleep-disordered breathing and related symptoms in 6- to 17-year old children--the Tucson Children’s Assessment of Sleep Apnea Study. J Pediatr. 2010;157:57-61 [PubMed]journal. [CrossRef] [PubMed]
 
Young T. .Peppard P.E. .Gottlieb D.J. . Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-1239 [PubMed]journal. [CrossRef] [PubMed]
 
Redline S. .Sanders M. . Hypopnea, a floating metric: implications for prevalence, morbidity estimates, and case finding. Sleep. 1997;20:1209-1217 [PubMed]journal. [PubMed]
 
Stradling J.R. .Barbour C. .Glennon J. .Langford B.A. .Crosby J.H. . Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women. J Sleep Res. 2000;9:381-388 [PubMed]journal. [CrossRef] [PubMed]
 
Ward K.L. .Hillman D.R. .James A. .et al Excessive daytime sleepiness increases the risk of motor vehicle crash in obstructive sleep apnea. J Clin Sleep Med. 2013;9:1013-1021 [PubMed]journal. [PubMed]
 
Redline S. .Yenokyan G. .Gottlieb D.J. .et al Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2010;182:269-277 [PubMed]journal. [CrossRef] [PubMed]
 
Peppard P.E. .Young T. .Palta M. .Skatrud J. . Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378-1384 [PubMed]journal. [CrossRef] [PubMed]
 
Marin J.M. .Agusti A. .Villar I. .et al Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2169-2176 [PubMed]journal. [PubMed]
 
Gottlieb D.J. .Yenokyan G. .Newman A.B. .et al Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010;122:352-360 [PubMed]journal. [CrossRef] [PubMed]
 
Gordon P. .Sanders M.H. . Sleep.7: positive airway pressure therapy for obstructive sleep apnoea/hypopnoea syndrome. Thorax. 2005;60:68-75 [PubMed]journal. [CrossRef] [PubMed]
 
Patel S.R. .White D.P. .Malhotra A. .Stanchina M.L. .Ayas N.T. . Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med. 2003;163:565-571 [PubMed]journal. [CrossRef] [PubMed]
 
Iber C. .Ancoli-Israel S. .Chesson A.L. Jr..Quan S.F. . American Academy of Sleep Medicine The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications.  2007;:- [PubMed] American Academy of Sleep Medicine Westchester, ILjournal
 
Berry R.B. .Budhiraja R. .Gottlieb D.J. . American Academy of Sleep Medicine; Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicineet al Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012;8:597-619 [PubMed]journal. [PubMed]
 
Young T. .Palta M. .Dempsey J. .Skatrud J. .Weber S. .Badr S. . The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235 [PubMed]journal. [CrossRef] [PubMed]
 
Palombini L.O. .Tufik S. .Rapoport D.M. .et al Inspiratory flow limitation in a normal population of adults in São Paulo, Brazil. Sleep. 2013;36:1663-1668 [PubMed]journal. [PubMed]
 
Young L.R. .Taxin Z.H. .Norman R.G. .Walsleben J.A. .Rapoport D.M. .Ayappa I. . Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. Sleep. 2013;36:405-412 [PubMed]journal. [PubMed]
 
Nieto F.J. .Young T.B. .Lind B.K. .et al Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283:1829-1836 [PubMed]journal. [CrossRef] [PubMed]
 
Van Dongen H.P. .Vitellaro K.M. .Dinges D.F. . Individual differences in adult human sleep and wakefulness: leitmotif for a research agenda. Sleep. 2005;28:479-496 [PubMed]journal. [PubMed]
 

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References

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine task force. Sleep. 1999;22:667-689 [PubMed]journal. [PubMed]
 
Peppard P.E. .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;177:1006-1014 [PubMed]journal. [CrossRef] [PubMed]
 
Goodwin J.L. .Vasquez M.M. .Silva G.E. .Quan S.F. . Incidence and remission of sleep-disordered breathing and related symptoms in 6- to 17-year old children--the Tucson Children’s Assessment of Sleep Apnea Study. J Pediatr. 2010;157:57-61 [PubMed]journal. [CrossRef] [PubMed]
 
Young T. .Peppard P.E. .Gottlieb D.J. . Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-1239 [PubMed]journal. [CrossRef] [PubMed]
 
Redline S. .Sanders M. . Hypopnea, a floating metric: implications for prevalence, morbidity estimates, and case finding. Sleep. 1997;20:1209-1217 [PubMed]journal. [PubMed]
 
Stradling J.R. .Barbour C. .Glennon J. .Langford B.A. .Crosby J.H. . Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women. J Sleep Res. 2000;9:381-388 [PubMed]journal. [CrossRef] [PubMed]
 
Ward K.L. .Hillman D.R. .James A. .et al Excessive daytime sleepiness increases the risk of motor vehicle crash in obstructive sleep apnea. J Clin Sleep Med. 2013;9:1013-1021 [PubMed]journal. [PubMed]
 
Redline S. .Yenokyan G. .Gottlieb D.J. .et al Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2010;182:269-277 [PubMed]journal. [CrossRef] [PubMed]
 
Peppard P.E. .Young T. .Palta M. .Skatrud J. . Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378-1384 [PubMed]journal. [CrossRef] [PubMed]
 
Marin J.M. .Agusti A. .Villar I. .et al Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2169-2176 [PubMed]journal. [PubMed]
 
Gottlieb D.J. .Yenokyan G. .Newman A.B. .et al Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010;122:352-360 [PubMed]journal. [CrossRef] [PubMed]
 
Gordon P. .Sanders M.H. . Sleep.7: positive airway pressure therapy for obstructive sleep apnoea/hypopnoea syndrome. Thorax. 2005;60:68-75 [PubMed]journal. [CrossRef] [PubMed]
 
Patel S.R. .White D.P. .Malhotra A. .Stanchina M.L. .Ayas N.T. . Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med. 2003;163:565-571 [PubMed]journal. [CrossRef] [PubMed]
 
Iber C. .Ancoli-Israel S. .Chesson A.L. Jr..Quan S.F. . American Academy of Sleep Medicine The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications.  2007;:- [PubMed] American Academy of Sleep Medicine Westchester, ILjournal
 
Berry R.B. .Budhiraja R. .Gottlieb D.J. . American Academy of Sleep Medicine; Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicineet al Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012;8:597-619 [PubMed]journal. [PubMed]
 
Young T. .Palta M. .Dempsey J. .Skatrud J. .Weber S. .Badr S. . The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235 [PubMed]journal. [CrossRef] [PubMed]
 
Palombini L.O. .Tufik S. .Rapoport D.M. .et al Inspiratory flow limitation in a normal population of adults in São Paulo, Brazil. Sleep. 2013;36:1663-1668 [PubMed]journal. [PubMed]
 
Young L.R. .Taxin Z.H. .Norman R.G. .Walsleben J.A. .Rapoport D.M. .Ayappa I. . Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. Sleep. 2013;36:405-412 [PubMed]journal. [PubMed]
 
Nieto F.J. .Young T.B. .Lind B.K. .et al Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283:1829-1836 [PubMed]journal. [CrossRef] [PubMed]
 
Van Dongen H.P. .Vitellaro K.M. .Dinges D.F. . Individual differences in adult human sleep and wakefulness: leitmotif for a research agenda. Sleep. 2005;28:479-496 [PubMed]journal. [PubMed]
 
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