Upper Airway Resistance Syndrome Is Not a Distinct Syndrome

Neil J. Douglas

Respiratory Medicine Unit, Department of Medicine, Royal Infirmary, Edinburgh, United Kingdom

	INTRODUCTION

TOP INTRODUCTION 1. DISTINCT DIAGNOSTIC CRITERIA 2. DIAGNOSTIC CRITERIA MUST... 3. DIAGNOSTIC CRITERIA MUST... 4. CONSEQUENT MORBIDITY CONCLUSION: IS THE UPPER... REFERENCES

The term "upper airway resistance syndrome" (UARS [1]) proved useful in highlighting deficiencies in the definition of the sleep apnea/hypopnea syndrome (SAHS). However, UARS is not distinct from SAHS, nor is there adequate evidence that UARS exists.

A syndrome is "a complex of signs and symptoms resulting from a common cause" (2). Thus, a distinct syndrome has distinct signs and symptoms. Patients with UARS usually have no signsabnormalities on physical examination (2)and the symptoms of UARS (1, 3) are identical to those for SAHS (4). Thus, UARS is not a distinct syndrome.

Having dismissed UARS on important semantic grounds, it is equally vulnerable medically. To be a distinct condition, it must have the following:

1. 1. Distinct diagnostic criteria
2. 2. Diagnostic criteria that are abnormal
3. 3. Diagnostic criteria that are specific
4. 4. Evidence of a causal link between the diagnostic abnormalities and clinical features (consequent morbidity)

UARS fails on all criteria.

	1. DISTINCT DIAGNOSTIC CRITERIA

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In the original description (1), diagnosis required sleepiness, a low apnea-hypopnea index (AHI), and frequent arousals. All reported sleepiness but no specific level of subjective or objective sleepiness was required. No subject "had obstructive sleep apnea syndrome as currently defined" but their AHI was not reported. They had to have at least 10 "short" arousals per hour slept. Esophageal pressure was not a diagnostic criterion for UARS (1). Criteria have been further complicatednot clarifiedby use of differing AHI thresholds (3, 5), the introduction of esophageal pressure criteria (6, 7), and the possible use of flattening of the flow-time profile to diagnose UARS (8).

Major diagnostic confusion about UARS centers on the scoring of hypopneas. Many centers have scored hypopneas from thermal sensors. These are excellent for detecting apneas, but poor for identifying hypoventilation; exhalations of 50 and 500 ml have identical temperature. Thus, when it was recognized that hypopneas and apneas had similar consequences, and it was recommended that hypopneas should be defined by semiquantative rather than thermal techniques (9) and these now include inductance plethysmography, nasal pressure, and pneumotachography (10). Those centers that use these methods to define hypopneas rarely, if ever, classify patients as having UARS, whereas centers that rely on thermal definitions report UARS frequently (5, 6, 11).

	2. DIAGNOSTIC CRITERIA MUST BE ABNORMAL

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Sleepiness

The threshold for significant sleepiness is based on self-reports and nearly 20% of women and about 7% of men in the normal population report sleepiness (12). An Epworth score of > 8 has been used (3), but the normal range is up to 12 or even 15 (13).

Low AHI

The criterion of low AHI is deliberately set to define normality.

Arousal

The arousal frequency used to define UARS, > 10 per hour, is normal on the first night of polysomnography whether without (median, 16 [95% confidence interval 6-33] per hour for age < 60 yr [14]) or with (mean, 24 [SD 12] per hour [7]) the sleep-disturbing effect of esophageal pressure monitoring. Thus, it is erroneous to use > 10 arousals per hour as a cutoff for abnormality in patients undergoing polysomnography (1, 5, 6). Indeed, all patients with UARS in some studies have normal arousal frequencies at < 30 per hour (3).

Negative Pleural Pressure

The addition of criteria requiring progressive falls in esophageal pressure seemed sensible, but such falls are not synonymous with increasing resistance, and may also result from increased ventilation. A decreasing pressure over 10 s (6) may mean as few as two consecutive breaths with increasing pressure generation and normal subjects have frequent such episodes, especially during rapid eye movement (REM) sleep (15).

Thus, all four criteria are common in the normal population.

	3. DIAGNOSTIC CRITERIA MUST BE SPECIFIC

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Sleepiness

Sleepiness is not specific to UARS.

Low AHI

AHI is low in all causes of sleepiness except for SAHS.

Arousal

Many sleep disorders including narcolepsy and periodic limb movement disorder have arousal frequencies in the range specified.

Thus, none of the three features of UARS is individually specific to the syndrome. Coexistence of all three is also not specific, as this is common in patients with other medical or psychological causes of their sleepiness. The addition of a pleural pressure condition seems unlikely to result in diagnostically useful specificity, as such episodes are also common in normal subjects (15).

	4. CONSEQUENT MORBIDITY

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Evidence for morbidity may come from epidemiological or intervention studies. There is no epidemiological evidence that UARS causes morbidity. The most robust interventional evidence comes from randomized controlled trials (16), but none have been performed in UARS. In a nonrandomized uncontrolled trial, patients with UARS had decreased symptoms, sleepiness, and arousals on continuous positive airway pressure (CPAP) (1). It is impossible to draw firm conclusions from decreased symptoms in an uncontrolled trial, particularly as placebo-controlled trials in SAHS have shown marked improvements in symptoms with placebo (17, 18). The decrease in arousal frequency from 31 (SD 13) per hour on diagnostic polysomnography to 8 (SD 2) per hour after CPAP looks superficially impressive. However, the CPAP results were obtained on each subject's sixth polysomnographic night and thus increased familiarity with sleeping while being monitored was a major confounder. There is certainly a need for a randomized placebo-controlled trial of patients fulfilling the criteria for UARS to determine whether this entity truly exists. Sleep medicine has suffered enough from evidence-based medicine "experts" (16) and the term "UARS" should not be used unless robust random controlled trial (RCT) evidence is gathered to show it exists.

Even if such evidence were gathered, it should not become a distinct syndrome, as it would be merely part of a disease spectrum that includes SAHS. I believe there should be a new name, possibly something like the respiratory arousal syndrome, to focus on the breathing problems causing sleep disruption. The importance of such all-inclusive terminology goes beyond semantics. The use of separate titles leads to confusion, particularly among nonspecialists, and to the misguided belief that the condition is entirely different from the remainder of the disease spectrum.

	CONCLUSION: IS THE UPPER AIRWAY RESISTANCE SYNDROME DISTINCT?

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Clearly, the answer is no. Patients with UARS have precisely the same symptoms as patients with SAHS. On overnight recordings, their "characteristic" respiratory and neurophysiological findings are normal. The continued use of the term to describe sleepy patients with an ill-defined constellation of sleep study findings allows it to be used as a dustbin term for the diagnostically destitute. The term "UARS" should be abandoned.

	References

TOP INTRODUCTION 1. DISTINCT DIAGNOSTIC CRITERIA 2. DIAGNOSTIC CRITERIA MUST... 3. DIAGNOSTIC CRITERIA MUST... 4. CONSEQUENT MORBIDITY CONCLUSION: IS THE UPPER... REFERENCES

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