What is Upper Airway Resistance Syndrome (UARS) and how is it diagnosed?

What is Upper Airway Resistance Syndrome (UARS)?

UARS is a form of sleep-disordered breathing now classified under obstructive sleep apnea (OSA) in which repetitive increases in upper airway resistance cause brief EEG arousals and daytime somnolence, without significant apneas, hypopneas, or oxygen desaturation. 1

Clinical Definition and Pathophysiology

• UARS represents a milder form on the spectrum of sleep-disordered breathing where patients have intact upper airway neurologic function and respond to minor changes in airway dimensions, unlike OSA patients who have local neurologic impairment 2

• The pathophysiology involves crescendo increases in negative intrathoracic pressure (≤ -12 cm H₂O) that stimulate mechanoreceptors in the upper airway, triggering brief EEG arousals that fragment sleep 3, 4

• UARS is now subsumed under the diagnosis of OSA in the International Classification of Sleep Disorders-3 (ICSD-3) given shared pathophysiology and response to treatment 1

Clinical Presentation

Primary Symptoms

• Excessive daytime sleepiness (EDS) is the hallmark symptom, resulting directly from repetitive EEG arousals rather than oxygen desaturation 3

• Most patients present with functional somatic syndromes rather than classic sleep complaints, leading them to seek psychiatric care rather than sleep evaluation 2

• Snoring may be absent in approximately 9% of UARS cases (termed "silent UARS"), making diagnosis particularly challenging 4

Associated Features

• Hypertension is an important sequela, likely resulting from autonomic and cardiovascular changes induced by increased negative intrathoracic pressure 3

• Patients typically have lower body mass index (mean BMI ~26) compared to classic OSA patients 5

• Common complaints include sensation of throat clearing, nasal congestion, or throat tickle, though these are nonspecific 1

Diagnostic Approach

Gold Standard Diagnosis

Polysomnography with esophageal manometry is the gold standard for diagnosing UARS 3, 4

Diagnostic Criteria on PSG:

• Apnea-Hypopnea Index (AHI) < 5 events/hour 5, 4
• Respiratory Effort-Related Arousal (RERA) index > 20 events/hour (some sources use ≥10/hour with total arousal index ≥10/hour) 5, 4
• Crescendo pattern of increasingly negative esophageal pressure (≤ -12 cm H₂O) terminated by brief EEG arousal, followed by normalization of esophageal pressure 4
• Absence of significant oxygen desaturation 5
• Presence of EDS (Epworth Sleepiness Scale typically >10) 5, 4

Scoring Methodology

• Calculate Respiratory Disturbance Index (RDI) which includes apneas, hypopneas, AND RERAs: RDI = (# apneas + # hypopneas + # RERAs) × 60 / total sleep time in minutes 1

• Arousal-based scoring is essential and must include hypopneas associated with EEG arousals (with or without oxygen desaturation) plus RERAs 1

Alternative Diagnostic Approach

• PAP titration can serve as both diagnostic and therapeutic tool in suspected UARS cases 5

• During PAP titration, patients with UARS require unexpectedly high pressures (mean ~7 cm H₂O) despite low AHI, providing evidence of increased upper airway resistance 5

• This "therapy-to-diagnosis" protocol simultaneously determines individual therapeutic pressures needed 5

Critical Diagnostic Pitfalls

Why UARS is Frequently Missed:

• Standard polysomnography without esophageal manometry will miss UARS because AHI appears normal (<5) 3, 2

• Home sleep apnea tests (HSAT) cannot diagnose UARS because they lack EEG monitoring for arousals and cannot measure esophageal pressure 1

• Patients often present to psychiatrists with functional somatic complaints rather than sleep specialists, leading to misdiagnosis as idiopathic hypersomnia or psychiatric disorders 2

• Absence of snoring does not exclude UARS—silent UARS occurs in ~9% of cases 4

• Normal oxygen saturation throughout the night is typical and should not reassure clinicians if EDS is present 5, 4

When to Suspect UARS:

• Patient with EDS (Epworth >10) but normal AHI on standard PSG 5, 4
• Young to middle-aged adults (mean age ~46) with normal or low BMI presenting with unexplained fatigue 5
• Patients with functional somatic syndromes and sleep complaints 2
• High arousal index (≥10/hour) with low respiratory disturbance index (<5/hour) on initial PSG 4

Diagnostic Algorithm

1. Screen with clinical history: EDS, functional somatic complaints, possible snoring (but absence doesn't exclude), normal/low BMI 5, 2

2. Perform standard PSG first: If AHI <5 but arousal index ≥10 and patient has EDS, proceed to step 3 4

3. Perform PSG with esophageal manometry: Look for crescendo negative inspiratory pressure ≤-12 cm H₂O terminated by EEG arousals, with RERA index >20 5, 4

4. Alternative approach if esophageal manometry unavailable: Perform PAP titration study—requirement for pressures ≥7 cm H₂O despite AHI <5 suggests UARS 5

Treatment Implications

• Nasal continuous positive airway pressure (CPAP) is the most efficacious therapy, though patient compliance may be challenging 3

• Treatment pressures determined during diagnostic PAP titration can be used as therapeutic pressures 5

• Oral appliances and radiofrequency ablation of palatal tissue show promise but require further validation 3

• Untreated UARS leads to progression of sleep-disordered breathing and development of comorbid conditions including hypertension 3, 6