Obstructive Sleep Apnea (OSA)

Less severe forms may not produce oxygen desaturation, but they interrupt sleep.

Obstructive sleep hypopnea is a condition in which inspiratory flow is diminished, but not absent, in a high resistance airway.

Upper airway resistance syndrome is crescendo snoring terminated by snorts and respiratory effort-related arousals (RERAs). Breathing reductions do not meet strict criteria for obstructive apneas and hypopneas. Patients with upper airway resistance syndrome are typically younger and have less obesity than those with OSA. Patients are more often female, report fatigue, and complain of insomnia. Snoring and upper airway airflow resistance cause noisy inspiration but without arousals from sleep lasting > 2 seconds. Symptoms, diagnostic evaluation, and treatment of snoring and upper airway resistance syndrome are similar to those of OSA.

Obstructive sleep apnea is the leading medical cause of excessive daytime sleepiness. A more correct term is wake-time excessive sleepiness, because people who work during the night may be excessively sleepy during night hours. The excessive sleepiness actively increases risk of automobile crashes, difficulties at work, and sexual dysfunction. There is often some degree of cognitive impairment and also increased risk of injury (eg, when operating heavy machinery or engaging in other activities during which unintentional sleep episodes would be hazardous). Relationships with bed partners, roommates, and/or housemates may also be adversely affected because such people may have difficulty sleeping because of the patient's noisy, restless sleep. Severe OSA (apnea-hypopnea index > 30 per hour) increases the risk of death in middle-aged men.

OSA also has medical risks unrelated to excessive sleepiness. Hypertension is strongly associated with OSA (2). Normotensive patients with untreated OSA are more likely to develop hypertension within 5 years of diagnosis. Repetitive nocturnal hypoxia and sleep disruption are associated with increased risk of medical disorders, including heart failure, atrial fibrillation (even after catheter ablation) and other arrhythmias, nonalcoholic fatty liver, and stroke (3). The risk of stroke and all-cause mortality is increased even when controlling for other risk factors (eg, hypertension, diabetes) (4). However, the contribution of OSA to these common disorders (and thus its cost to society) is often underappreciated (5).

In addition, perioperative complications, including cardiac arrest, occur with unrecognized OSA, because moderate and general anesthesia is a risk for airway obstruction. Patients should inform an anesthesiologist of the diagnosis before undergoing any surgery and should receive continuous positive airway pressure (CPAP) when they receive preoperative drugs and during recovery.

1. 1. Zinchuk AV, Gentry M , Concato J, et al: Phenotypes in obstructive sleep apnea: A definition, examples and evolution of approaches. Sleep Med Rev 35:113-123, 2017. doi: 10.1016/j.smrv.2016.10.002

2. 2. Van Ryswyk E, Mukherjee S, Chai-Coetzer CL, et al: Sleep disorders, including sleep apnea and hypertension. Am J Hypertens 31(8):857-864, 2018. doi: 10.1093/ajh/hpy082

3. 3. Zinchuk AV, Jeon S, Koo BB, et al: Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea. Thorax 73(5):472–480, 2018. doi: 10.1136/thoraxjnl-2017-210431

4. 4. Yaggi HK, Concato J, Kernan WN, et al: Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 353(19):2034-2041, 2005. doi:10.1056/NEJMoa043104

5. 5. Borsoi L, Armeni P, Donin G, et al: The invisible costs of obstructive sleep apnea (OSA): Systematic review and cost-of-illness analysis. PLoS One 17(5):e0268677, 2022. doi: 10.1371/journal.pone.0268677

1. 1. Patel SR: Obstructive sleep apnea. Ann Intern Med 171(11):ITC81-ITC96, 2019. doi: 10.7326/AITC201912030

2. 2. Yi M, Tan Y, Pi Y, et al: Variants of candidate genes associated with the risk of obstructive sleep apnea. Eur J Clin Invest 52(1):e13673, 2022. doi: 10.1111/eci.13673

1. 1. Lee JJ, Sundar KM: Evaluation and management of adults with obstructive sleep apnea syndrome. Lung 199(2):87-101, 2021. doi: 10.1007/s00408-021-00426-w

2. 2. Strohl KP, Redline S. Recognition of obstructive sleep apnea. Am J Respir Crit Care Med 154(2 Pt 1):279-89, 1996. doi: 10.1164/ajrccm.154.2.8756795. PMID: 8756795.

Sleep studies include

• Traditional polysomnography conducted in a sleep laboratory

• Portable diagnostic tools that can be used by patients at home in their own bed

Polysomnography records and helps classify stages of sleep and the occurrence and duration of apneic and hypopneic periods. It is ideal for confirming the diagnosis of OSA and quantifying the severity of OSA. However, it requires an overnight stay in a sleep laboratory and is thus complicated and expensive. Polysomnography typically includes

• Continuous measurement of sleep architecture by EEG (electroencephalography)

• Chin electromyography to detect hypotonia

• Electro-oculography to assess the occurrence of rapid eye movements.

• Airflow sensors at the nose and mouth to detect apneas and hypopneas

• Chest and/or abdominal sensors to detect respiratory effort

• Oxygen saturation by pulse oximetry

• ECG monitoring to detect arrhythmias associated with apneic episodes

The patient is also observed by video.

Other variables evaluated include limb muscle activity (to assess nonrespiratory causes of sleep arousal, such as restless legs syndrome and periodic limb movements disorder) and body position, because apnea may occur predominantly in the supine position.

The apnea-hypopnea index (AHI) is the total number of episodes of apnea and hypopnea occurring during sleep divided by the hours of sleep time. It is a common measure of respiratory disturbance during sleep and is used to classify the severity of OSA. Note the AHI alone does not determine need for treatment.

OSA is graded as:

• Mild: AHI ≥ 5 and < 15 per hour

• Moderate: AHI ≥ 15 and ≤ 30 per hour

• Severe: AHI > 30 per hour

Some patients may have a very high AHI (> 60).

The respiratory disturbance index (RDI) is a related measure that includes the number of arousals related to respiratory effort (called respiratory effort-related arousals or RERAs) plus the number of apnea and hypopnea episodes per hour of sleep.

The arousal index, which is the number of arousals per hour of sleep, can be computed if EEG monitoring is used. The arousal index is loosely correlated with the apnea-hypopnea index and respiratory disturbance index; about 20% of apneas and desaturation episodes are not accompanied by arousals, or other causes of arousals are present.

However, the apnea-hypopnea index, arousal index, and respiratory disturbance index are only moderately associated with a patient’s symptoms. Some patients with a high or extremely high AHI (eg, > 60) have few or no symptoms. Additional metrics and combinations of metrics may prove useful in diagnosis (6). Furthermore, studies now show that it is a composite of clinical and polysomnographic data (not just AHI) that are linked to outcome and to cardiovascular risk and mortality, for instance, sleepiness regardless of AHI is linked to excess cardiovascular disease.

Home sleep testing using portable diagnostic tools uses a limited subset of polysomnographic measures, typically just heart rate, pulse oximetry, respiratory effort, position, and nasal airflow to detect apnea and estimate its severity. Their role is expanding (7) because of their convenience and decreased cost and their ability to provide a reasonably accurate estimate of respiratory disturbances during sleep.

However, portable tools have some limitations. They do not actually detect the presence of sleep and instead depend on patients to self-report sleeping, which can be inaccurate; if patients were not sleeping during part of the study and they did not report this, sleep-disordered breathing will be underestimated. Also, coexisting sleep disorders (eg, restless legs syndrome, seizures, REM behavior disorder, confusional arousals) are not detected. Follow-up polysomnography may still be needed to characterize these disorders as well as to accurately provide AHI and RDI values in the different stages of sleep and with changes in position, especially when surgery or therapy other than positive airway pressure is being considered.

Portable tools are often used in combination with questionnaires (eg, STOP-Bang, Berlin Questionnaire). If questionnaire results indicate a higher pre-test probability of disease, the sensitivity and specificity of the portable tools is higher.

1. 1. Gupta A, Quan SF, Oldenburg O, et al: Sleep-disordered breathing in hospitalized patients with congestive heart failure: a concise review and proposed algorithm. Heart Fail Rev 23(5):701-709, 2018. doi:10.1007/s10741-018-9715-y

2. 2. Gamaldo C, Buenaver L, Chernyshev O, et al: Evaluation of clinical tools to screen and assess for obstructive sleep apnea. J Clin Sleep Med 14(7):1239-1244, 2018. doi:10.5664/jcsm.7232

3. 3. Keenan BT, Kirchner HL, Veatch OJ, et al: Multisite validation of a simple electronic health record algorithm for identifying diagnosed obstructive sleep apnea. J Clin Sleep Med 16(2):175–183, 2020. doi: 10.5664/jcsm.8160

4. 4. Keenan BT, Kim J, Singh B, et al: Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis. Sleep 41(3):zsx214, 2018. doi: 10.1093/sleep/zsx214

5. 5. Lovejoy CA, Abbas AR, Ratneswaran D: An introduction to artificial intelligence in sleep medicine. J Thorac Dis 13(10):6095-6098, 2021. doi:10.21037/jtd-21-1569

6. 6. Malhotra A, Ayappa I, Ayas N, et al: Metrics of sleep apnea severity: beyond the apnea-hypopnea index. Sleep 44(7):zsab030, 2021. doi: 10.1093/sleep/zsab030

7. 7. Collop NA, Anderson WM, Boehlecke B, et al: Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. J Clin Sleep Med 3(7):737-47, 2007.

1. 1. Bratton DJ, Gaisl T, Wons AM, et al: CPAP vs mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis. JAMA 314(21):2280-2293, 2015. doi:10.1001/jama.2015.16303

Initial treatment aims to control risk factors such as obesity, hypertension, alcohol use, and sedative use. Exercise decreases the AHI and increases alertness, independent of any effect on body mass index (BMI).

Daytime sleepiness can be reduced by good sleep hygiene measures, including sleeping longer and discontinuing sedative drugs, particularly antihistamines or antidepressants.

Modest weight loss (≥ 15%) may result in clinically meaningful improvement (2, 3) but should not be considered curative for OSA. However, weight loss is extremely difficult for most people, especially those who are fatigued or sleepy. Bariatric surgery, however performed, is an option that frequently reverses symptoms and improves AHI in 85% of OSA patients with severe obesity (BMI ≥ 40); however, the degree of improvement may not be as great as the degree of weight loss.

CPAP is the treatment of choice for most patients with OSA and subjective daytime sleepiness, including those in whom it causes cognitive impairment (4, 5). There are reports of racial and socioeconomic bias in making this treatment available.

There are many different CPAP devices available, including those that cover the nose, nose and mouth, or the whole face. All have cushions to provide an air seal, which is essential for maintaining a pressure gradient. Cushions may be inflatable or made of silicone, foam, or gel. Proper fit and comfort vary widely among patients but must be optimized for both efficacy and adherence.

CPAP improves upper airway patency by applying positive pressure to the collapsible upper airway segment. Effective pressures typically range from 3 to 15 cm H2O. Pressure requirements are not correlated with disease severity. Many CPAP devices monitor CPAP efficacy and titrate pressures automatically, according to internal algorithms. If necessary, polysomnographic monitoring can be used to guide manual titration of pressure.

Although a reduction in AHI is one of the treatment goals, CPAP will reduce cognitive impairment and improve quality of life regardless of improvement in the AHI. CPAP also may reduce blood pressure. If CPAP is withdrawn, symptoms recur over several days, though short interruptions of therapy for acute medical conditions are usually well tolerated. Duration of therapy is indefinite.

If clinical improvement is not apparent, CPAP adherence should be reviewed, and patients should be reassessed for a second sleep disorder (eg, upper airway obstruction) or a comorbid disorder. If patients have septal deviation or polyps, nasal surgery may make CPAP treatment more successful but inconsistently “treats” OSA.

Adverse effects of nasal CPAP include discomfort resulting from a poorly fitting mask, and dryness and nasal irritation, which can be alleviated in some cases with the use of warm humidified air. However, newer mask designs have improved comfort and ease of use.

Adherence is difficult for many people and is lower in patients who do not experience sleepiness. Overall, about 50% of patients adhere to use of CPAP long term. Adherence can be improved by efforts to foster a positive attitude towards device use combined with early attention to any problems, particularly mask fit, and close follow-up by a committed caretaker, with reinforcement by the primary care physician. There is also a need to recognize and address the decreased long-term CPAP adherence among patients who do not have obesity and have low respiratory arousal threshold (ie, awaken easily) and thus a propensity for increased arousals and irregular breathing.

Even when adherence is adequate, results may become unsatisfactory if patient factors change (eg, weight gain, nasal obstruction develops).

CPAP can be augmented with inspiratory assistance (bilevel positive airway pressure) to increase tidal volume in patients with comorbid obesity-hypoventilation syndrome.

Oral appliances are designed to advance the mandible or, at the very least, prevent retrusion and tongue prolapse during sleep (6,7, 8). Some appliances are designed to pull the tongue forward. These appliances are now considered mainstream treatments of both snoring and mild to moderate OSA. Comparisons of appliances to CPAP show equivalent effectiveness in mild to moderate OSA, but cost-effectiveness studies are focused on fixed initial costs of fabrication, rather than replacement and follow-up costs.

Surgical procedures to correct anatomic factors, such as enlarged tonsils and nasal polyps contributing to upper airway obstruction (called anatomic procedures), should be considered (8, 9). Surgery for macroglossia or micrognathia is also an option. Surgery is a first-line treatment if specific anatomic encroachment is identified. However, in the absence of encroachment, evidence to support surgery as a first-line treatment is lacking.

Uvulopalatopharyngoplasty (UPPP) was previously the most common procedure. It involves resection of pharyngeal tissue. UPPP has been largely replaced by less aggressive approaches that attempt to stabilize the lateral walls of the pharynx and/or enlarge the velopharyngeal area without risk of altering speech or swallowing. Equivalence with CPAP was shown in one study using CPAP as a bridge to surgery, but the interventions have not been directly compared. Results are less predictable in patients who have severe obesity or anatomic narrowing of the airway. The procedure may reduce intrusive snoring, although apneic episodes may remain as severe (although silent) as before surgical intervention.

Other surgical procedures include midline glossectomy, hyoid advancement, and mandibulomaxillary advancement. Mandibulomaxillary advancement is sometimes offered as a 2nd-stage procedure if soft tissue approaches are not curative. The optimal multistage approach is not known.

Tracheostomy is the most effective therapeutic maneuver for OSA but is done as a last resort. It bypasses the site of obstruction and is indicated for patients most severely affected (eg, those with cor pulmonale).

Upper airway stimulation using an implanted device to stimulate a branch of the hypoglossal nerve (10, 11) can activate muscles that protrude the tongue and other muscles that help open the airway. This therapy is now mainstream, being successful in selected patients with moderate to severe disease. It is used mainly in those who are unable to tolerate CPAP therapy and in whom oral appliances are ineffective. The procedure may also be tried in those in whom mandibulomaxillary advancement is contemplated. Improvements in AHI to < 10 per hour occur in about 65% of these selected patients, but symptoms may improve without achieving efficacy in an AHI < 20 per hour.

Various adjunctive treatments are sometimes used but have no proven benefit for OSA.

Supplemental oxygen improves blood oxygenation and may reduce AHI and arousal index among patients who did not respond to upper airway surgery (12), but a beneficial clinical effect is mainly in those with high gain (tendency to have repeated apnea or hypopnea after an initial episode) and effects are hard to predict. Also, oxygen may provoke respiratory acidosis and morning headache.

13, 14, 15).

16), but cannot be recommended because of factors including limited experience, a low therapeutic index, lack of replication of results, and lack of adequate trials. Better methods to recognize sleep apnea subtypes may allow better selection of patients for this line of treatment.

Exercises for upper airway muscles (myofunctional therapy) have been proposed on the theory that improved muscle strength and tone might help improve airway patency during sleep (17). There are a number of exercises that seem to reduce AHI and symptoms, making this approach interesting, particularly because it is noninvasive and with no adverse effects. However, this approach is not yet a mainstream recommendation, because of the wide variety of techniques proposed and the uncertainly about their mechanism of action and efficacy, combined with the great practical difficulties with adherence.

Nasal dilatory devices and throat sprays sold over-the-counter for snoring have not been studied sufficiently to prove value in OSA.

Laser-assisted uvuloplasty, uvular splints, and radiofrequency tissue ablation have been used to treat snoring in patients without OSA. Although they may transiently decrease snoring loudness, efficacy in treating OSA is neither predictable nor durable.

An informed patient and family are better able to cope with an OSA treatment strategy, including tracheostomy. Patient support groups provide helpful information and effectively support timely treatment and follow-up. There is now organized investigation on the role of patient support groups and digital support tools for management (18).

1. 1. Strohl KP, Cherniack NS, Gothe B: Physiologic basis of therapy for sleep apnea. Am Rev Respir Dis 134(4):791-802, 1986. doi: 10.1164/arrd.1986.134.4.791

2. 2. Joosten SA, Hamilton GS, Naughton MT: Impact of weight loss management in OSA. Chest 152(1):194-203, 2017. doi: 10.1016/j.chest.2017.01.027

3. 3. Kuna ST, Reboussin DM, Strotmeyer ES, et al: Effects of weight loss on obstructive sleep apnea severity. Ten-year results of the Sleep AHEAD study. Am J Respir Crit Care Med 203(2):221-229, 2021. doi: 10.1164/rccm.201912-2511OC

4. 4. Labarca G, Saavedra D, Dreyse J, et al: Efficacy of CPAP for improvements in sleepiness, cognition, mood, and quality of life in elderly patients with OSA: systematic review and meta-analysis of randomized controlled trials. Chest 158(2):751-764, 2020. doi: 10.1016/j.chest.2020.03.049

5. 5. Wang G, Goebel JR, Li C, et al: Therapeutic effects of CPAP on cognitive impairments associated with OSA. J Neurol 267(10):2823-2828, 2020. doi: 10.1007/s00415-019-09381-2

6. 6. Ng JH, Yow M: Oral appliances in the management of obstructive sleep apnea. Sleep Med Clin 14(1):109-118, 2019. doi: 10.1016/j.jsmc.2018.10.012

7. 7. Ramar K, Dort LC, Katz SG, et al: Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015. J Clin Sleep Med 11(7):773-827, 2015. doi: 10.5664/jcsm.4858

8. 8. Randerath W, Verbraecken J, de Raaff CAL, et al: European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea. Eur Respir Rev 30(162):210200, 2021. doi: 10.1183/16000617.0200-2021

9. 9. Halle TR, Oh MS, Collop NA, et al: Surgical treatment of OSA on cardiovascular outcomes: a systematic review. Chest 152(6):1214-1229, 2017. doi: 10.1016/j.chest.2017.09.004

10. 10. Woodson BT, Strohl KP, Soose RJ, et al: Upper airway stimulation for obstructive sleep apnea: 5-year outcomes. Otolaryngol Head Neck Surg 159(1):194-202, 2018. doi:10.1177/0194599818762383

11. 11. Baptista PM, Costantino A, Moffa A, et al: Hypoglossal nerve stimulation in the treatment of obstructive sleep apnea: Patient selection and new perspectives. Nat Sci Sleep 12:151–159, 2020. doi: 10.2147/NSS.S221542

12. 12. Joosten SA, Tan M, Wong AM, et al: A randomized controlled trial of oxygen therapy for patients who do not respond to upper airway surgery for obstructive sleep apnea. J Clin Sleep Med 17(3):445-452, 2021. doi: 10.5664/jcsm.8920

13. 13. Lal C, Weaver TE, Bae CJ, et al: Excessive daytime sleepiness in obstructive sleep apnea. Mechanisms and clinical management. Ann Am Thorac Soc 18(5):757-768, 2021. doi: 10.1513/AnnalsATS.202006-696FR

14. 14. Black JE, Hirshkowitz M: Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 28(4):464-471, 2005. doi:10.1093/sleep/28.4.464

15. 15. Hirshkowitz M, Black JE, Wesnes K, et al: Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med 101(3):616-627, 2007. doi:10.1016/j.rmed.2006.06.007

16. 16. Taranto-Montemurro L, Messineo L, Wellman A: Targeting endotypic traits with medications for the pharmacological treatment of obstructive sleep apnea. A review of the current literature. J Clin Med 8(11):1846, 2019. doi: 10.3390/jcm8111846

17. 17. Camacho M, Certal V, Abdullatif J, et al: Myofunctional therapy to treat obstructive sleep apnea: a systematic review and meta-analysis. Sleep 38(5):669-75, 2015. doi: 10.5665/sleep.4652

18. 18. Aardoom JJ, Loheide-Niesmann L, Ossebaard HC, et al: Effectiveness of eHealth interventions in improving treatment adherence for adults with obstructive sleep apnea: meta-analytic review. J Med Internet Res 22(2):e16972, 2020. doi: 10.2196/16972