Sleep-related breathing disorder

Sleep-related breathing disorders (SRBD) are a group of conditions in which breathing is abnormal during sleep, including obstructive sleep apnoea, central sleep apnoea, obesity hypoventilation syndrome, congenital central hypoventilation syndrome, sleep-related hypoxaemia and hypoventilation, and isolated symptoms such as snoring and catathrenia. Their common feature is sleep-related hypoventilation or apnoea causing intermittent hypoxaemia, hypercapnia and sleep fragmentation, with cardiovascular and neurocognitive consequences through sympathetic activation, endothelial dysfunction and metabolic disturbance. A 2019 literature-based model estimated that about 936 million adults aged 30 to 69 years have at least mild obstructive sleep apnoea and about 425 million have moderate to severe disease, a burden far larger than previously recognised.

Terminology and classification

• Obstructive sleep apnoea (OSA) is recurrent upper airway collapse during sleep with continued respiratory effort, so polysomnography shows thoracic and abdominal movement without effective airflow.
• Central sleep apnoea (CSA) is characterised by absent respiratory effort, is common in heart failure, stroke and opioid use, and reflects abnormal carbon dioxide sensitivity or unstable ventilatory drive.
• Obesity hypoventilation syndrome (OHS) is defined by obesity with awake hypercapnia after exclusion of other causes, and obstructive events often coexist while weight loss alone may not restore ventilatory drive.
• Congenital central hypoventilation syndrome (CCHS) is caused by PHOX2B variants and produces failure of autonomic breathing control during sleep and sometimes while awake, and it is rare, coded as ORPHA:661.
• Sleep-related hypoxaemia emphasises hypoxaemia rather than the apnoea index and is common in chronic lung and neuromuscular disease, so diagnosis and follow-up cannot rely on the apnoea-hypopnoea index alone.
• Medication or substance-related sleep hypoventilation occurs with opioids, benzodiazepines and alcohol, and the drug history is essential because dose reduction is often the first intervention.
• Snoring and catathrenia are isolated symptoms rather than disease entities, and when respiratory events and daytime symptoms coexist the case belongs to a sleep-related breathing disorder.
• ICD-10 places sleep apnoea at G47.3 within sleep disorders, and subtypes require additional codes or clinical description.
• ICD-11 places sleep-related breathing disorders in chapter 07 at 7A4, with obstructive sleep apnoea at 7A41, and central apnoea, hypoventilation and hypoxaemia have separate entries.
• MeSH uses D012891 for sleep apnoea syndromes, a broad node that requires free-text terms such as obstructive sleep apnoea, sleep disordered breathing and hypoventilation for adequate retrieval.
• Chinese literature uses several labels, and OSAHS differs from OSA because the former includes hypopnoea in the same entity, so abbreviations should not be treated as interchangeable.
• The apnoea-hypopnoea index (AHI) and the respiratory disturbance index (RDI) are not equivalent, because RDI also counts arousal-related respiratory effort, and study comparisons must state the metric.
• The group is not a single entity but a set of syndromes defined by mechanism and ventilatory pattern, and mixed apnoea is common in heart failure and chronic opioid use.
• Paediatric disease differs from adult disease, with predominantly obstructive events related to adenotonsillar hypertrophy and central events more common in preterm infants and neuromuscular disease.

History

• In 1836 Dickens described the obese boy Joe falling asleep repeatedly in The Pickwick Papers, a literary image later used to name obesity hypoventilation syndrome.
• In 1956 Burwell and colleagues reported obese patients with alveolar hypoventilation, introduced the Pickwickian concept and linked obesity, somnolence and hypercapnia.
• Around 1965 European teams described recurrent cessation of breathing during sleep using polygraphic recording, turning OSA from clinical observation into a measurable event.
• In the 1970s Remmers and colleagues proposed a mechanical model of upper airway collapse, reframing OSA as an imbalance between pharyngeal anatomy and muscle tone.
• In 1981 Sullivan and colleagues reported that nasal continuous positive airway pressure reversed obstructive sleep apnoea, and the technique became first-line therapy worldwide.
• In 1981 Fujita and colleagues described uvulopalatopharyngoplasty, the first systematic operation for OSA, although long-term efficacy remained limited.
• Through the 1980s and 1990s polysomnography standardised the simultaneous recording of EEG, eye movements, muscle tone, airflow, respiratory effort and oxygen saturation.
• The American Academy of Sleep Medicine published its first scoring manual in 1993, with revisions in 1999 and 2007 that changed AHI rules and limited comparability of historical data.
• In 2014 the third edition of the International Classification of Sleep Disorders made sleep-related breathing disorders a separate chapter and clarified hypoventilation, hypoxaemia and isolated symptoms.
• In 2014 the United States approved hypoglossal nerve stimulation for OSA on the basis of the STAR trial, bringing neuromodulation into sleep medicine.
• In 2019 Benjafield and colleagues estimated that nearly one billion adults have at least mild OSA, greatly raising public health awareness.
• In 2023 the third edition of the International Classification of Sleep Disorders was revised with updated paediatric rules, hypopnoea definitions and comorbidity entries.
• In 2024 the SURMOUNT-OSA trial showed that tirzepatide substantially reduced AHI and improved symptoms in moderate to severe OSA, and the drug was subsequently approved in the United States for OSA with obesity.
• From literary description to home ventilators and then neuromodulation and pharmacotherapy, the history reflects how technology has continually widened diagnostic thresholds and treatment targets.

Epidemiology

• The 2019 model by Benjafield and colleagues estimated about 936 million adults aged 30 to 69 years with at least mild OSA and about 425 million with moderate to severe disease, with China, the United States, Brazil and India carrying the largest numbers.^[1]
• The same analysis estimated about 176 million adults with moderate to severe OSA in China, yet diagnosis and treatment rates remain very low because laboratory capacity and public awareness are limited.
• United States community cohorts report moderate to severe OSA in about 13% of men and 6% of women aged 30 to 70, and the obesity epidemic has raised these figures over two decades.^[2]
• Men are affected two to three times more often than women, and prevalence rises sharply after menopause, when fat distribution and hormonal changes alter risk and symptoms shift towards fatigue and insomnia.
• Age is the most consistent risk factor, as pharyngeal fat deposition, tissue elasticity and ventilatory stability change over time, and prevalence can exceed 20% in older adults.
• Paediatric OSA affects about 1% to 5% of children, peaks in the preschool years, is mainly driven by adenotonsillar hypertrophy and is more common in obesity.
• Obesity is the most important modifiable risk, and a 10% weight gain raises AHI by about 30% while a 10% loss lowers it by about 26%.
• Craniofacial restriction in retrognathia, micrognathia, macroglossia and short neck is a key mechanism, and Asian populations have higher OSA risk at the same body mass index.
• Nasal obstruction from rhinitis, sinusitis and septal deviation increases inspiratory negative pressure and promotes pharyngeal collapse, and treating the nose can improve tolerance of therapy.
• Alcohol, benzodiazepines and opioids reduce pharyngeal muscle tone and arousal threshold, and bedtime alcohol is a common cause of worse overnight hypoxaemia.
• Smoking increases risk through upper airway inflammation and oedema, and cessation lowers cardiovascular risk even when anatomy is unchanged.
• Hypothyroidism, acromegaly and Cushing syndrome increase risk through soft tissue or ventilatory changes, so endocrine assessment is needed in atypical or refractory cases.
• Pregnancy increases snoring and OSA through weight gain, airway oedema and diaphragmatic elevation, and it is associated with hypertension, pre-eclampsia and fetal growth restriction.
• Undiagnosed disease may reach 80%, contributing to traffic accidents, occupational error and cardiovascular events, while the economic case for population screening remains uncertain.
• Costs include direct medical care and lost productivity, and United States estimates attribute many billions of dollars each year to sleep disorders, with higher admission and drug costs in severe OSA.

Pathophysiology

• The core mechanism of OSA is upper airway narrowing combined with reduced pharyngeal dilator tone during sleep, so negative inspiratory pressure collapses the pharyngeal wall.
• Collapsibility depends on airway area, tissue compliance and muscle responsiveness, and parapharyngeal fat, a small skeletal frame and tongue base prolapse all lower closing pressure.
• High loop gain makes ventilation overreact to carbon dioxide fluctuations and produces periodic hyperventilation followed by central apnoea, especially in heart failure and at altitude.
• Repeated apnoea causes intermittent hypoxaemia and reoxygenation, activating sympathetic tone, oxidative stress and systemic inflammation, which impair endothelial function and insulin sensitivity.
• Sleep fragmentation from recurrent arousals disrupts slow-wave and rapid eye movement sleep, producing daytime sleepiness, inattention and mood disturbance even when total sleep time is normal.
• Marked negative intrathoracic pressure during obstructive events raises venous return and right heart load and promotes atrial enlargement and atrial fibrillation.
• Intermittent hypoxaemia accelerates atherosclerosis through hypoxia-inducible factor and inflammasome pathways, and animal models show larger and less stable plaques.
• Central apnoea in heart failure typically produces Cheyne-Stokes respiration, in which prolonged circulation time and enhanced chemosensitivity create periodic ventilatory oscillation and worse prognosis.
• OHS involves reduced chest wall compliance, increased diaphragmatic load and inadequate central drive, and awake hypercapnia distinguishes it from pure OSA.
• CCHS is caused by polyalanine repeat expansion or point variants in PHOX2B, and defective autonomic responses to hypercapnia and hypoxia make mechanical ventilation necessary during sleep.^[3]
• Phenotyping divides OSA into anatomical, muscle responsiveness, arousal threshold and loop gain dominance, and the response to CPAP, oral appliances and neuromodulation differs across phenotypes.
• The natural course is a continuum from snoring to mild and then moderate to severe disease with cardiovascular complications, and progression depends on weight, age and comorbidity.
• Paediatric pathophysiology centres on adenotonsillar hypertrophy and craniofacial growth, and chronic mouth breathing can produce adenoid facies while hypoxaemia and fragmentation affect growth and learning.
• Residual sleepiness after treatment suggests irreversible neurocognitive injury, coexisting sleep insufficiency or another sleep disorder and should not be attributed only to poor adherence.

Clinical features

• Snoring is the most common symptom, but snoring alone is not OSA, and loudness correlates poorly with event severity and cannot be used for screening.
• Witnessed apnoea is a specific history, and reports from a bed partner are often more reliable than self-report, as are nocturnal choking, gasping and awakening.
• Daytime sleepiness is the core symptom, and an Epworth score above 10 is abnormal, although many patients report fatigue or poor concentration rather than sleep attacks.
• Morning headache, dry mouth, nocturia and unrefreshing sleep are common, and nocturia relates to atrial natriuretic peptide and negative intrathoracic pressure and often improves with treatment.
• Complications include at least hypertension, atrial fibrillation, stroke, heart failure, type 2 diabetes, metabolic syndrome, depression and cognitive impairment, with the strongest evidence for hypertension and atrial fibrillation.
• OSA is a common cause of secondary hypertension, and about half of patients with resistant hypertension have moderate to severe OSA, while CPAP lowers blood pressure modestly and improves nocturnal dipping.
• Atrial fibrillation initiation and maintenance are linked to OSA, and screening and treating OSA before ablation improves sinus rhythm maintenance in many electrophysiology centres.
• Stroke risk rises with AHI through nocturnal blood pressure swings, atrial fibrillation, endothelial dysfunction and a procoagulant state, yet screening after stroke remains underused.
• Diabetes and insulin resistance show a dose-response relation, and intermittent hypoxaemia impairs insulin sensitivity independently of obesity, while CPAP produces modest but meaningful glycaemic benefit.
• Children present with mouth breathing, snoring, restless sleep, enuresis and poor growth, and long-term effects include attention deficits, learning difficulty and behavioural problems that improve after adenotonsillectomy.
• Atypical presentations are common, with falls, cognitive decline and nocturia in older adults, snoring and raised blood pressure in pregnancy, and Cheyne-Stokes respiration in heart failure.
• Severe disease and death arise mainly from cardiovascular events, malignant arrhythmia and traffic accidents, and all-cause mortality in severe OSA is about two to three times that of comparable controls.
• Occupational risk in drivers, pilots and shift workers relates to sleepiness, and screening and adherence regulation are written into law in some countries.

Diagnosis

• Diagnosis requires both respiratory event evidence and clinical symptoms, and the management of asymptomatic AHI elevation is debated, with the 2023 revision emphasising symptoms, comorbidity and patient values.
• Polysomnography is the reference standard, recording EEG, eye movements, chin tone, airflow, respiratory effort, oxygen saturation, position and ECG, and it separates obstructive from central events and describes sleep architecture.
• Home sleep apnoea testing suits patients with a high pretest probability of moderate to severe disease and no major comorbidity, but it is less reliable in central apnoea, lung disease and neuromuscular disease.
• AHI categories are below 5 normal, 5 to 15 mild, 15 to 30 moderate and 30 or more severe, and paediatric thresholds differ from adult thresholds.
• The 2017 American Academy of Sleep Medicine diagnostic guideline recommends sleep testing for suspected OSA and rejects questionnaire or home oximetry alone for diagnosis.^[4]
• The STOP-BANG score of 3 or more indicates high risk and the Epworth scale quantifies sleepiness, and the combination improves preoperative and primary care screening.
• The oxygen desaturation index and minimum saturation add information, and nocturnal hypoxaemia may correlate with cardiovascular risk better than event counts alone.
• Differential diagnosis includes at least simple snoring, central sleep apnoea, obesity hypoventilation, narcolepsy, insufficient sleep syndrome, depression, hypothyroidism, nocturnal asthma, gastro-oesophageal reflux and periodic limb movement disorder.
• The ratio of central to obstructive events must be established before treatment, because CPAP works for both but central events may need adaptive servo-ventilation or cause-directed therapy.
• Narcolepsy presents with irresistible sleep, cataplexy and early REM sleep, and the multiple sleep latency test is key because misdiagnosis as OSA delays treatment.
• Nocturnal asthma and reflux cause awakenings and cough, and oesophageal impedance and lung function help distinguish them, while either can coexist with OSA.
• Screening should cover resistant hypertension, atrial fibrillation, heart failure, stroke, morbid obesity and preoperative patients, and occupational drivers and pilots are assessed under regulation.
• Diagnostic delay is common because of waiting lists, stigma around snoring and neglect of daytime sleepiness, and home and remote testing can partly relieve the bottleneck.
• Paediatric diagnosis combines history, examination, tonsillar size and sleep testing, and drug-induced sleep endoscopy can localise obstruction but is not routine.

Management

• Treatment aims to abolish respiratory events, correct hypoxaemia, restore sleep quality and daytime function and reduce cardiovascular and metabolic risk rather than to lower a number.
• CPAP is first-line for moderate to severe adult OSA, first reported by Sullivan in 1981 and recommended as standard by the 2019 American Academy of Sleep Medicine guideline.^[5][6]
• Adherence limits effectiveness, with only about 30% to 60% of patients using CPAP for more than four hours per night, and mask discomfort, nasal dryness and claustrophobia are common causes.
• Oral appliances advance the mandible to enlarge the pharyngeal space and suit mild to moderate OSA or CPAP intolerance, although long-term use can alter occlusion and stress the temporomandibular joint.
• Positional therapy helps supine-dependent OSA, and avoidance devices and behavioural change reduce events, but long-term adherence and evidence are limited.
• Weight loss is fundamental, and lifestyle, intensive behavioural programmes and bariatric surgery all lower AHI, with a 10% weight loss usually producing about a 25% AHI reduction.
• Tirzepatide reduced AHI and improved blood pressure and inflammatory markers in the 2024 SURMOUNT-OSA trial and was subsequently approved for OSA with obesity, bringing pharmacotherapy into the pathway.^[7]
• Uvulopalatopharyngoplasty suits tonsillar hypertrophy and soft palate collapse, but the AHI response varies widely and preoperative selection determines outcome.^[8]
• Adenotonsillectomy is first-line for most children with OSA, with clear gains in behaviour, growth and quality of life, and residual disease requires reassessment.
• Maxillomandibular advancement enlarges the airway through skeletal advancement, suits craniofacial deformity and CPAP failure, and is more effective than soft tissue surgery but more invasive.
• Hypoglossal nerve stimulation maintains tongue protrusion with respiration-synchronised stimulation, was approved in 2014 and suits CPAP failure with suitable anatomy and response.^[9]
• Adaptive servo-ventilation treats central apnoea and Cheyne-Stokes respiration, but caution is needed in reduced ejection fraction heart failure because the SERVE-HF trial raised a mortality signal.
• Acetazolamide can be used at altitude or for selected central events, while progesterone and theophylline have limited evidence, and no drug replaces positive airway pressure.
• Prevention includes weight control, avoiding alcohol and sedatives at bedtime, treating nasal obstruction, sleeping in the lateral position and maintaining regular sleep schedules.
• Prognosis depends on severity, adherence and comorbidity, and CPAP improves sleepiness, blood pressure and quality of life although cardiovascular primary prevention evidence is inconsistent, and the SAVE trial showed no hard endpoint benefit.^[10]

Research and controversies

• Cardiovascular protection from CPAP is the central controversy, as SAVE showed no secondary prevention benefit in patients with established cardiovascular disease, implicating adherence, selection and follow-up duration.
• Whether mild OSA should be treated is disputed, with one side favouring early intervention and the other warning about overdiagnosis and medicalisation, and the 2023 revision emphasises shared decisions.
• Phenotype-guided therapy is emerging, selecting CPAP, oral appliances, surgery or neuromodulation by anatomy, muscle responsiveness, arousal threshold and loop gain, but practical phenotyping is not widely available.
• The long-term safety, rebound after withdrawal and cardiovascular outcomes of pharmacotherapy are unknown, and tirzepatide approval has raised concern that drugs might replace CPAP.
• Long-term outcomes, device durability and reoperation rates for hypoglossal nerve stimulation are still accumulating, and selection criteria are not standardised.
• Home testing improves access but risks false negatives, limited channels and scoring variability, so guidelines remain cautious about indications.
• Paediatric scoring rules and treatment thresholds lack consensus, and the management of mild disease and residual disease after surgery varies between countries.
• Sleep laboratory capacity is severely limited in low-resource settings, and simplified screening and low-cost testing are public health priorities without locally validated thresholds.
• Digital health and remote CPAP management can improve adherence, but privacy, algorithmic transparency and liability remain unresolved.
• Occupational screening raises privacy and employment discrimination concerns, and balancing public safety against individual rights is a policy dispute.
• Unmet needs include biomarkers that predict CPAP adherence, therapies that reverse neurocognitive injury, long-term paediatric follow-up and affordable global diagnostic tools.
• Guideline disagreement centres on AHI thresholds, home testing indications and interpretation of cardiovascular prevention evidence, and recommendations differ in strength across societies, so local resources must guide practice.