Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, characterized by recurrent upper airway obstruction during sleep. It is an independent risk factor for various systemic diseases such as hypertension, diabetes, coronary heart disease, and stroke, and is also a significant cause of traffic accidents.
Epidemiology
The prevalence of obstructive sleep apnea in adults is 2% - 4%. Globally, there are approximately 936 million patients with OSA, with a higher incidence in males than in females. The prevalence increases significantly in postmenopausal females and older adults.
Etiology and pathogenesis
The pathogenesis of obstructive sleep apnea is complex. Some patients have anatomical narrowing of the upper airway, such as nasal polyps, deviated nasal septum, enlarged tonsils, enlarged tongue, and micrognathia. Additionally, abnormal neuromuscular function of the pharynx, local oxidative stress and inflammation, and genetic factors also contribute to the condition.
High-risk factors for OSA include obesity, males, alcohol consumption, administration of sedatives or muscle relaxants, and advanced age. Certain conditions, such as hypothyroidism, acromegaly, heart failure, stroke, gastroesophageal reflux, and neuromuscular diseases, can also lead to obstructive sleep apnea.
During sleep, these factors can cause complete or partial upper airway obstruction, leading to apnea or hypopnea. Following apnea or hypopnea, blood oxygen levels drop and carbon dioxide levels rise, stimulating the respiratory center and causing arousal or microarousal, which reopens the upper airway, ending the apnea or hypopnea. Subsequently, blood oxygen and carbon dioxide levels return to normal, allowing patients to fall asleep again, initiating the next cycle of apnea or hypopnea. The repeated cycles constitute obstructive sleep apnea.
Pathophysiology
The main pathophysiological changes caused by obstructive sleep apnea include chronic intermittent hypoxia, sleep fragmentation, and sympathetic nervous system activation, which can affect multiple systems such as respiratory, circulatory, and endocrine systems.
OSA patients are mostly obese, which leads to restrictive ventilatory dysfunction and hypoxia. Sleep apnea exacerbates hypoxemia and may be accompanied by hypercapnia. Over time, some patients may experience reduced blood oxygen levels and elevated carbon dioxide pressure even when awake. If patients have other respiratory conditions like COPD or asthma, these conditions can be aggravated.
In normal individuals, blood pressure decreases during sleep. However, during apnea, transient blood pressure elevations can occur, disrupting normal blood pressure rhythms. This is related to recurrent hypoxemia, hypercapnia, significant intrathoracic pressure changes, frequent arousal responses, and sympathetic nervous system activation during sleep. Some OSA patients experience arrhythmias, mainly manifested by sinus bradycardia, sinus arrest, atrioventricular block, and parasympathetic overactivity during apnea. Upon resumption of breathing, there is increased sympathetic activity, often causing tachycardia and sudden death in severe cases. Hypoxia during sleep apnea can also raise pulmonary arterial pressure, and persistent pulmonary hypertension can lead to chronic cor pulmonale.
OSA primarily leads to increased sympathetic activity, causing hypothalamic-pituitary-adrenal axis dysfunction and disrupting normal hormonal rhythms, often resulting in insulin resistance, promoting diabetes occurrence.
Long-term chronic intermittent hypoxia can cause secondary polycythemia and thrombosis. Repeated awakenings, reduced deep sleep, and sleep fragmentation can impair brain function, leading to mental, neurological, and behavioral abnormalities, promoting cognitive dysfunction. Intrathoracic pressure fluctuations can also cause gastroesophageal reflux. Due to recurrent oxidative stress and chronic inflammation, OSA may also promote tumor development and metastasis.
Clinical manifestations
Common symptoms of obstructive sleep apnea include irregular snoring during sleep, repeated episodes of apnea and arousal, morning headaches, xerostomia, daytime drowsiness, and amnesia. Some patients may experience nocturia, hypogonadism, and enuresis. Severe patients can present with psychological, intellectual, and behavioral abnormalities, often associated with hypertension, coronary heart disease, arrhythmias (especially bradycardia-tachycardia syndromes), heart failure, chronic cor pulmonale, stroke, type 2 diabetes, insulin resistance, kidney dysfunction, and non-alcoholic liver damage. Therefore, patients with these comorbidities should be carefully evaluated.
Physical examination includes recording height and weight to calculate body mass index (BMI), measuring blood pressure (both before sleep and upon waking), neck circumference, and assessing craniofacial features (focusing on retrognathia or micrognathia). Nasal and pharyngeal examinations are also conducted to detect conditions causing upper airway stenosis, such as enlarged uvula, tonsils, tongue, and adenoids. Due to the risk of cardiovascular and cerebrovascular complications, relevant examinations of the heart, lungs, and nervous system should be performed based on clinical symptoms.
Laboratory and other examinations
Auxiliary test includes:
- Complete blood count (some patients may have elevated red blood cells and hemoglobin)
- Blood glucose and lipids (elevated blood glucose and lipids may also be observed in some patients)
- Arterial blood gas analysis (hypoxemia and elevated carbon dioxide pressure may be present)
- Electrocardiogram (ECG) (arrhythmias may be detected)
- Pulmonary function test (some patients may have restrictive ventilatory dysfunction)
- Cephalometric x-ray (including pharyngeal x-ray)
Polysomnography (PSG) is the gold standard for diagnosing OSA. Standard monitoring involves at least 7 hours of sleep, recording EEG, EMG, oral and nasal airflow, thoracoabdominal movements, oxygen saturation, and ECG to accurately assess the severity and type of sleep apnea. If PSG is not available, portable monitoring devices can be used for initial screening.
Diagnosis
The diagnosis is primarily based on medical history, signs, and polysomnography results. Clinically, typical symptoms include snoring and sleep apnea during nighttime sleep, along with daytime symptoms such as drowsiness. Polysomnography shows an apnea-hypopnea index (AHI) ≥ 5 events per hour, predominantly obstructive sleep apnea events. Alternatively, even in the absence of daytime symptoms, an AHI ≥ 10 events per hour with obstructive events and damage to one or more major organs can confirm the diagnosis.
Table 1 Severity classification of OSA
Severity can be classified based on AHI and the minimum nocturnal arterial oxygen saturation (SaO2). Since AHI and oxygen saturation changes in some patients are not parallel in clinical practice, it is recommended to use AHI as the primary standard for assessing severity, while noting the level of hypoxemia.
Differential diagnosis
Obstructive sleep apnea should be differentiated from snoring, upper airway resistance syndrome, and narcolepsy.
Snoring
Snoring is characterized by loud, regular snoring sound during sleep. Polysomnography shows AHI < 5 events per hour, with no significant hypoxemia during sleep.
Upper airway resistance syndrome
Upper airway resistance syndrome presents with increased upper airway resistance during sleep, with polysomnography showing repeated α waves and more than 10 microarousals per hour, disrupting sleep continuity. Patients may experience fatigue and daytime drowsiness, with or without noticeable snoring, without apnea and hypoxemia.
Narcolepsy
Narcolepsy is mainly characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations, mostly in adolescents, with some cases having a family history. In addition to typical cataplexy symptoms, the main diagnostic criterion is a mean sleep latency < 8 minutes with ≥ 2 abnormal rapid eye movement sleep behaviors during multiple sleep latency test. When differentiating, it is important to inquire about family history, age of onset, main symptoms, and polysomnography results. Narcolepsy and obstructive sleep apnea can be concurrent, so careful diagnosis is necessary.
Treatment
Proper treatment of obstructive sleep apnea (OSA) not only improves quality of life but also reduces complications and improves prognosis.
Etiological treatment
Underlying diseases that cause or exacerbate OSA should be treated. For instance, hypothyroidism can be treated with thyroxine.
Behavioral intervention
Patients can be guided to control diet and lose weight, maintain good sleep hygiene, primarily sleep in lateral decubitus position, and avoid risk factors such as smoking, alcohol consumption (especially at night), and administration of sedatives and hypnotics.
Obesity is a major risk factor for OSA, and effective weight management can reduce disease severity.
Smoking can irritate the upper airway, leading to widespread mucosal edema and exacerbating snoring. Alcohol reduces central nervous system sensitivity to hypoxia and carbon dioxide, decreasing pharyngeal muscle tone and causing airway obstruction.
OSA is more common in supine position, and sleeping in lateral decubitus position can reduce the AHI.
Noninvasive positive pressure ventilation (NIPPV)
Common NIPPVs include continuous positive airway pressure (CPAP), automatic CPAP, and bilevel positive airway pressure (BiPAP). CPAP is the first-line treatment for moderate to severe OSA. It works by delivering continuous positive pressure to keep the airway open throughout the breathing cycle, effectively reducing upper airway obstruction and preventing cardiovascular events. Auto-CPAP and BiPAP can be used for patients who cannot tolerate CPAP, and BiPAP is recommended for patients with significant CO2 retention. Pressure titration should be performed to select the appropriate pressure and mode before starting PAP therapy.
Indications for CPAP therapy include:
- Moderate to severe OSA
- Mild OSA with significant symptoms (daytime drowsiness, cognitive impairment, depression) or comorbid cardiovascular diseases and diabetes
- Persistent OSA after other treatments like uvulopalatopharyngoplasty or oral appliances.
- Overlap syndrome (OSA with COPD)
- Perioperative treatment for OSA
Contraindications for CPAP therapy include:
- Lung bullae on chest x-ray or CT
- Pneumothorax or mediastinal emphysema
- Significant hypotension or shock
- Hemodynamic instability in acute myocardial infarction
- Cerebrospinal fluid leaks, head trauma, or intracranial pneumatosis
- Uncontrolled acute otitis media, rhinitis, or sinusitis
- Glaucoma
Oral appliances
Oral appliances are devices that advance the mandible to expand the pharyngeal airway and improve obstruction, and are indicated in patients with simple snoring and mild to moderate OSA, especially in patients with retrognathia. They can be used in patients who cannot tolerate CPAP, are unsuitable for surgery, or have unsatisfactory surgical outcomes.
Surgical intervention
Surgery is not the initial treatment for moderate to severe OSA due to risks and benefits, and indications should be strictly followed. It is believed that surgery is only indicated in patients where surgery can clearly relieve upper airway obstruction, mainly with oropharyngeal obstruction, including thickened pharyngeal mucosa, narrow pharyngeal cavity, enlarged uvula, low soft palate, and enlarged tonsils, and AHI < 20 events per hour. Surgery is not recommended for obese patients or those with AHI >20 events per hour. Surgical options include uvulopalatopharyngoplasty and its modifications, and mandibular advancement surgery.
Other treatments
Medications for OSA are still absent. New methods such as upper airway muscle training and hypoglossal nerve or upper airway muscle stimulation have been tried with mixed results and require further evaluation for appropriate indications.