Residency · Residency · Respirology

Sleep-Disordered Breathing - OSA and CSA

Obstructive Sleep Apnea (OSA)

Epidemiology

Obstructive sleep apnea affects 10-30% of the adult population, with an estimated 80-90% of cases remaining undiagnosed. Major risk factors include obesity (BMI exceeding 30), male sex with a male-to-female ratio of 2-3:1, age older than 50, neck circumference exceeding 40 cm, craniofacial abnormalities, and family history. The Wisconsin Sleep Cohort study documented OSA with an AHI of 5 or greater in 24% of men and 9% of women, with moderate-to-severe disease (AHI 15 or greater) in 10% of men and 3% of women. The population-based HypnoLaus study subsequently demonstrated that the prevalence of moderate-to-severe OSA is even higher than previously estimated.

Pathophysiology

OSA results from upper airway collapse during sleep, determined by the balance between anatomic factors (structural narrowing of the pharynx) and neuromuscular factors (reduced pharyngeal dilator muscle tone during sleep). The critical closing pressure (Pcrit), defined as the pressure at which the upper airway collapses, quantifies airway collapsibility, with higher Pcrit indicating a more collapsible airway. The PALM model identifies four key phenotypic traits contributing to OSA: Pcrit/anatomy, arousal threshold, loop gain, and muscle responsiveness. The consequences of repetitive airway collapse include intermittent hypoxia, sleep fragmentation, intrathoracic pressure swings, sympathetic activation, systemic inflammation, and oxidative stress.

Clinical Consequences

The cardiovascular consequences of OSA are substantial. Resistant hypertension demonstrates a particularly strong association, with OSA present in 70-80% of patients with resistant hypertension. Atrial fibrillation carries an odds ratio of 2-4 in OSA patients. Heart failure, stroke, and coronary artery disease are all associated with untreated OSA. Metabolic consequences include insulin resistance, type 2 diabetes, and metabolic syndrome. Neurocognitive effects encompass excessive daytime sleepiness, impaired concentration, depression, and a 2-7 fold increased risk of motor vehicle accidents. Severe untreated OSA is associated with increased all-cause and cardiovascular mortality.

Diagnosis

Polysomnography (PSG) is the gold standard diagnostic test, measuring EEG, EOG, EMG, airflow (nasal pressure and thermistor), respiratory effort (thoracoabdominal belts), SpO2, body position, leg EMG, ECG, and snoring. Home sleep apnea testing (HSAT) using Type III devices that measure airflow, effort, and SpO2 is acceptable for uncomplicated patients with high pretest probability, but underestimates the AHI because these devices cannot measure total sleep time in the absence of EEG. A negative HSAT does not rule out OSA. The apnea-hypopnea index (AHI) quantifies disease severity: mild OSA is defined as AHI 5-15, moderate as AHI 15-30, and severe as AHI exceeding 30. An apnea requires 90% or greater airflow reduction for 10 seconds or more, while a hypopnea (AASM recommended definition) requires 30% or greater airflow reduction for 10 seconds or more with either 3% or greater oxygen desaturation or an arousal.

Screening Tools

The STOP-BANG questionnaire assesses Snoring, Tiredness, Observed apnea, Pressure (hypertension), BMI exceeding 35, Age exceeding 50, Neck circumference exceeding 40 cm, and Gender (male). A score of 3 or greater indicates high risk, and a score of 5 or greater indicates high probability of moderate-to-severe OSA. The Epworth Sleepiness Scale (ESS) quantifies subjective sleepiness, with a score exceeding 10 suggesting excessive daytime sleepiness and a score exceeding 16 indicating severe sleepiness.

<image>A detailed polysomnography tracing showing a 2-minute epoch of obstructive sleep apnea. Display channels from top to bottom: EEG (C3-A2, C4-A1), EOG, chin EMG, nasal pressure (showing airflow cessation), oral thermistor, thoracic effort belt (showing continued/paradoxical effort during apnea), abdominal effort belt (showing continued effort), SpO2 channel (showing desaturation from 95% to 82% following the apnea), body position indicator, and ECG. Label the obstructive apnea event (cessation of airflow with continued respiratory effort), the associated arousal on EEG, and the subsequent recovery breath. Compare with a brief inset showing a central apnea (cessation of both airflow AND effort) for contrast.</image>

OSA Management

CPAP (Continuous Positive Airway Pressure)

CPAP is the first-line therapy for moderate-to-severe OSA, functioning as a pneumatic splint that maintains upper airway patency. Effective CPAP adherence is defined as use for 4 or more hours per night on 70% or more of nights (Medicare definition), though clinical benefit increases with greater usage. Titration is performed either through in-laboratory PSG titration or with auto-titrating CPAP (APAP) using a pressure range of 4-20 cmH2O. CPAP consistently improves sleepiness, with ESS reductions of 2-4 points, and provides modest blood pressure reduction of 2-3 mmHg, with greater reductions in resistant hypertension and adherent patients. The SAVE trial, a secondary prevention study, demonstrated no significant reduction in composite cardiovascular events with CPAP in patients without excessive sleepiness, though compliance was suboptimal at a mean of 3.3 hours per night. Quality of life is significantly improved. Interface options include nasal masks, nasal pillows, and oronasal (full-face) masks, with nasal interfaces preferred for lower leak and better tolerance, and oronasal masks reserved for mouth breathers.

Alternative and Adjunctive Therapies

Mandibular advancement devices (MAD), custom-fitted by a dental sleep specialist, are effective for mild-to-moderate OSA and are non-inferior to CPAP for cardiovascular outcomes as demonstrated in the ORCHID trial, which showed equivalent blood pressure reduction. They also serve as an option for CPAP-intolerant patients. Positional therapy addresses supine-predominant OSA through vibrotactile sensors or the tennis ball technique, though long-term adherence is limited. Hypoglossal nerve stimulation (Inspire) is a surgically implanted device that stimulates cranial nerve XII to protrude the tongue during inspiration. The STAR trial demonstrated a 68% reduction in AHI at 12 months, with eligibility criteria including moderate-to-severe OSA (AHI 15-65), CPAP failure, BMI below 35, and absence of complete concentric collapse on drug-induced sleep endoscopy (DISE). Weight loss of 10% is associated with an approximately 26% AHI reduction, and bariatric surgery can dramatically reduce AHI by 50-80%, though it is not curative in most patients. Surgical options include uvulopalatopharyngoplasty (UPPP) with variable success rates of 40-60%, maxillomandibular advancement (MMA) as the most effective surgical procedure with AHI reduction exceeding 80%, tonsillectomy when tonsillar hypertrophy is present, and multilevel surgery. Pharmacotherapy is emerging as a potential treatment paradigm, with the SURMOUNT-OSA trial demonstrating that tirzepatide, a GLP-1 receptor agonist, reduced AHI by 51-63% versus placebo in obese OSA patients, though it is not yet FDA-approved for this indication.

Central Sleep Apnea (CSA)

Classification

Central sleep apnea encompasses several distinct entities. CSA with Cheyne-Stokes respiration (CSR) is associated with heart failure, present in 50% of patients with HFrEF, and characterized by a crescendo-decrescendo breathing pattern driven by high loop gain. Treatment-emergent CSA (complex sleep apnea) describes central apneas that emerge after initiation of CPAP for OSA, occurring in 5-15% of patients starting PAP therapy, and often resolving spontaneously within weeks to months. Narcotic and opioid-induced CSA is dose-dependent, with morphine-equivalent doses exceeding 200 mg per day associated with high prevalence, producing an ataxic or irregular breathing pattern. High-altitude CSA results from hyperventilation-induced hypocapnia during periodic breathing at altitudes above 2500 meters. Idiopathic CSA is rare and characterized by a low PaCO2 near or below the apneic threshold.

Pathophysiology

The pathophysiology of CSA centers on an unstable ventilatory control system with high loop gain. Loop gain, defined as the ratio of ventilatory response to the disturbance that provoked it, determines system stability: high loop gain results in an exaggerated ventilatory response to small perturbations, producing overshooting and undershooting oscillations around the apneic threshold. When PaCO2 falls below the apneic threshold, a central apnea occurs, during which CO2 rises, triggering an exaggerated ventilatory response that drives PaCO2 back below threshold, perpetuating the cycle. In heart failure, increased circulation time amplifies the oscillation, fluid shifts to the lungs increase plant gain, and pulmonary congestion stimulates vagal afferents.

CSA-CSR in Heart Failure

CSA-CSR is present in 30-50% of patients with HFrEF and is associated with worse prognosis independent of ejection fraction. The SERVE-HF trial in 2015 demonstrated that adaptive servo-ventilation (ASV) in patients with HFrEF (EF of 45% or less) and predominant CSA increased both all-cause and cardiovascular mortality (hazard ratio 1.28), establishing that ASV is contraindicated in HFrEF with EF of 45% or less. The CAT-HF trial similarly showed no benefit of ASV in acute decompensated heart failure with CSA. The current approach prioritizes optimization of heart failure therapy with guideline-directed medical therapy (ARNI, SGLT2 inhibitor, beta-blocker, mineralocorticoid receptor antagonist), which may reduce CSA-CSR as cardiac function improves. CPAP provides modest AHI reduction in CSA-CSR but no mortality benefit as demonstrated in the CANPAP trial, though post hoc analysis suggested possible benefit when AHI was suppressed below 15. Supplemental oxygen reduces AHI in CSA but lacks outcomes data. Phrenic nerve stimulation (remede system) is FDA-approved for moderate-to-severe CSA and was evaluated in the REMEDIE trial, which showed a 50% AHI reduction, and is used for CSA refractory to other treatments.

Treatment-Emergent CSA

Initial management involves observation for 8-12 weeks, as many cases resolve spontaneously with continued CPAP therapy. If persistent, switching to ASV is an option but only if the ejection fraction exceeds 45%, given the SERVE-HF contraindication. Bilevel PAP without a backup rate is an alternative.

<image>A comparative diagram showing the pathophysiology and polysomnographic patterns of OSA vs. CSA with Cheyne-Stokes respiration. Left panel (OSA): show upper airway anatomy with pharyngeal collapse, paradoxical chest/abdominal effort during apnea, and PSG tracing showing preserved effort bands during airflow cessation. Right panel (CSA-CSR): show intact upper airway with no collapse, central drive failure, and PSG tracing showing crescendo-decrescendo airflow pattern with simultaneous cessation of effort during central apneas. Include loop gain concept diagram in the center showing the ventilatory control feedback loop with plant gain, controller gain, and how high loop gain leads to instability. At bottom, show a treatment comparison table: OSA (CPAP, MAD, surgery, HNS, weight loss) vs. CSA-CSR (optimize HF therapy, CPAP, phrenic nerve stimulation; ASV contraindicated if EF <= 45%).</image>

Overlap Syndromes and Special Populations

OSA-COPD Overlap

The overlap of OSA and COPD affects 10-15% of COPD patients and produces worse nocturnal desaturation, more pulmonary hypertension, and higher mortality than either disease alone. CPAP combined with long-term oxygen therapy improves survival in the overlap syndrome. The overlap should be considered in COPD patients presenting with excessive sleepiness, morning headaches, or polycythemia disproportionate to their daytime PaO2.

OSA in Pregnancy

The prevalence of OSA increases during pregnancy due to weight gain, edema, and hormonal changes. OSA in pregnancy is associated with gestational hypertension, preeclampsia, gestational diabetes, and preterm birth. CPAP is safe in pregnancy, with auto-titrating devices preferred as pressure requirements change across trimesters.

Key Clinical Pearls

• A negative home sleep apnea test does NOT exclude OSA; if clinical suspicion remains high, proceed to in-laboratory PSG (HSAT underestimates AHI)
• ASV is CONTRAINDICATED in patients with heart failure and EF <= 45% (SERVE-HF: increased cardiovascular mortality); always check EF before prescribing ASV
• GLP-1 receptor agonists (tirzepatide) reduced AHI by 51-63% in obese OSA patients (SURMOUNT-OSA); pharmacotherapy for OSA may become a reality
• Hypoglossal nerve stimulation (Inspire) requires DISE (drug-induced sleep endoscopy) to confirm absence of complete concentric palatal collapse; it is not effective in all OSA patients
• The SAVE trial showed no cardiovascular benefit of CPAP in OSA patients without excessive sleepiness and with only 3.3 hours/night average use; CPAP adherence is critical for outcomes

References

1. Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687-698.
2. McEvoy RD, Antic NA, Heeley E, et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016;375(10):919-931. (SAVE)
3. Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N Engl J Med. 2015;373(12):1095-1105. (SERVE-HF)
4. Strollo PJ Jr, Soose RJ, Maurer JT, et al. Upper-Airway Stimulation for Obstructive Sleep Apnea. N Engl J Med. 2014;370(2):139-149. (STAR)
5. Malhotra A, Grunstein RR, Engleman HM, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024;391(14):1288-1300. (SURMOUNT-OSA)

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