Upper Airway Resistance Syndrome

Upper airway resistance syndrome is a sleep disordered breathing condition in which repeated increases in upper airway resistance during sleep cause brief arousals (respiratory effort related arousals) and fragmented sleep, with snoring and daytime symptoms, but without frank apnoeas, hypopnoeas or significant oxygen desaturation. The apnoea hypopnoea index is below 5 events per hour, and the respiratory arousal index is 5 or more per hour.

• It sits on a spectrum between simple snoring and obstructive sleep apnoea. Many sleep physicians now regard it as a mild form of obstructive sleep apnoea, and the distinction depends on how breathing events are scored (a hypopnoea scored with an arousal criterion makes many cases obstructive sleep apnoea).
• The mechanism is a narrow, collapsible pharyngeal airway with increased negative intrathoracic pressure during inspiration, which triggers a micro arousal before true collapse occurs. Sleep fragmentation follows.
• Typical patients are young to middle aged, often lean or of normal weight (body mass index below 25 to 30), and frequently women. Anatomical contributors include a narrow or high arched palate, a small or retruded jaw, a long soft palate, nasal obstruction (a deviated septum, turbinate hypertrophy, nasal valve collapse), tonsil enlargement and a posteriorly placed tongue.
• Associations: functional somatic syndromes (fibromyalgia, irritable bowel syndrome, chronic fatigue), orthostatic intolerance with low blood pressure, cold hands and feet, headaches and insomnia.
• Prevalence is uncertain, but it may affect 2 to 8% of adults presenting with unexplained sleepiness and fatigue. It is under recognised.

• Daytime fatigue, sleepiness, poor concentration, unrefreshing sleep, morning headache, mood symptoms, and often insomnia (difficulty maintaining sleep) rather than overt sleepiness. The score on a sleepiness scale is often normal or only mildly raised (below 10 of 24).
• Snoring that is light or absent. Noisy, effortful breathing is reported by a partner in some patients, and apnoeas are not witnessed.
• Other features: nocturia, bruxism, dry mouth, sleep onset and maintenance insomnia, restless sleep, cold extremities, low blood pressure with dizziness on standing, and non-restorative sleep despite adequate time in bed.
• Examination: often a normal body mass index, a narrow and high arched palate, a crowded oropharynx (class 3 or 4), retrognathia, nasal obstruction, and tonsillar hypertrophy. Blood pressure is low or normal.
• Differential diagnosis: obstructive sleep apnoea, primary snoring, insomnia disorder, idiopathic hypersomnia, narcolepsy, periodic limb movement disorder, restless legs syndrome, depression, hypothyroidism, anaemia, chronic fatigue syndrome, fibromyalgia, medicine effects (sedatives, antihistamines, antidepressants), and circadian rhythm disorders.
• Red flags: sleepiness while driving or in a safety critical job, witnessed apnoeas, resistant hypertension, atrial fibrillation, heart failure, stroke, daytime hypercapnia, and new onset symptoms with weight loss, voice change or a neck mass.
• Complications: chronic fatigue, impaired work and driving performance, mood disorders, and an uncertain contribution to cardiovascular disease.

• Clinical suspicion in a patient with snoring, fatigue or sleepiness and insomnia and no explanation, with a normal apnoea hypopnoea index on a screening test.
• Overnight attended polysomnography is the best test. A home sleep apnoea test based on oxygen saturation and flow often misses the condition, because there is no desaturation and no apnoea.
• Polysomnography with a respiratory arousal index of 5 or more events per hour, a low apnoea hypopnoea index (below 5 per hour), flow limitation on the nasal pressure signal (flattened inspiratory flow), and arousals linked to increased respiratory effort. Oesophageal pressure monitoring, the reference method, shows crescendo negative pressure swings before arousal, but is used only in research and specialist centres.
• Rule out other causes of sleepiness: full blood count, ferritin, thyroid function tests, glucose, vitamin D, and review medicines. Screen for depression and anxiety. A multiple sleep latency test is used when narcolepsy or idiopathic hypersomnia is suspected.
• ENT assessment with nasendoscopy to identify nasal and pharyngeal obstruction, and dental or orthodontic review for jaw structure.

• Conservative measures:
  • Weight optimisation where body mass index is above 25 (a weight loss of 5 to 10%), regular exercise, a regular sleep schedule of 7 to 9 hours, and avoidance of alcohol for at least 4 hours before bed.
  • Avoid sedatives, benzodiazepines and sedating antihistamines at night.
  • Positional therapy for supine dependent symptoms: side sleeping, a raised head of the bed by 10 to 15 cm, or a positional device.
  • Nasal care: saline irrigation, and fluticasone propionate nasal spray 50 micrograms per spray, 2 sprays into each nostril once daily for 4 to 8 weeks for allergic or non-allergic rhinitis, and nasal dilator strips for nasal valve collapse.
• Continuous positive airway pressure, set at a low pressure of 4 to 8 cm of water by auto titration, is the most effective treatment and improves sleepiness, fatigue and sleep quality. Aim for use for more than 4 hours per night on 70% or more of nights, with a humidifier and a comfortable mask. Review at 1 week, 1 month and 3 months.
• Oral appliance: a custom made mandibular advancement device, fitted by a dentist, moves the lower jaw forward and enlarges the airway. It suits patients who cannot tolerate positive airway pressure. Review dental effects every 6 to 12 months.
• Myofunctional therapy (tongue and oropharyngeal exercises for 15 to 20 minutes daily for 3 months) reduces snoring and respiratory events modestly.
• Surgery in selected patients with a defined anatomical obstruction after failed conservative therapy: septoplasty or turbinate reduction for nasal obstruction, tonsillectomy for tonsil enlargement, palatal surgery, and maxillomandibular advancement for craniofacial deficiency. Results are less predictable than for positive airway pressure.
• Medicines: no drug treats the airway. Modafinil 100 to 200 mg orally in the morning may be used for residual sleepiness in specialist care after other causes are excluded and the airway is treated. Treat insomnia with cognitive behavioural therapy, and avoid hypnotic drugs where possible.
• Special groups:
  • Pregnancy: encourage side sleeping and treat nasal congestion with saline and budesonide nasal spray (64 micrograms per spray, 2 sprays into each nostril once daily). Positive airway pressure is safe when needed.
  • Children: adenotonsillar hypertrophy is the main cause, and adenotonsillectomy is first line when symptoms and enlarged tonsils or adenoids are present. A short course of intranasal mometasone (50 micrograms per spray, 1 spray into each nostril once daily, age 3 to 11 years) and montelukast 4 mg (age 2 to 5 years) or 5 mg (age 6 to 14 years) at night for 12 weeks can be used for mild disease.
  • Drivers and safety critical workers: advise against driving when sleepy, and arrange urgent assessment.
  • Elderly: review sedating medicines and consider cardiac disease.
• Follow up: review at 4 to 12 weeks after starting treatment with symptoms, sleepiness scores and adherence data. Repeat polysomnography for persistent symptoms. Refer to a sleep physician for a suspected diagnosis, persistent fatigue despite treatment, and failure of conservative measures.