Obstructive Sleep Apnea

Jennifer M. Slowik; Abdulghani Sankari; Jacob F. Collen; Abdulghani Sankari

Obstructive Sleep Apnea

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Free Review Questions

Continuing Education Activity

Obstructive sleep apnea (OSA) is characterized by episodes of complete collapse of the airway or partial collapse with an associated decrease in oxygen saturation or arousal from sleep. This disturbance results in fragmented, nonrestorative sleep. OSA has significant implications for cardiovascular health, mental illness, quality of life, and driving safety. This activity reviews the cause and pathophysiology of obstructive sleep apnea and highlights the role of the interprofessional team in its management.

Objectives:

Describe the pathophysiology of obstructive sleep apnea.
Review the presentation of a patient with obstructive sleep apnea.
Summarize the treatment options for obstructive sleep apnea.
Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by obstructive sleep apnea.

Introduction

Obstructive sleep apnea (OSA) is characterized by episodes of a complete (apnea) or partial collapse (hypopnea) of the upper airway with an associated decrease in oxygen saturation or arousal from sleep.[1] This disturbance results in fragmented, nonrestorative sleep. Other symptoms include loud, disruptive snoring, witnessed apneas during sleep, and excessive daytime sleepiness.[2][3][4] OSA has significant implications for cardiovascular health,[5] mental illness, quality of life, and driving safety.

Etiology

Pharyngeal narrowing and closure during sleep is a complex phenomenon, and likely multiple factors play a role in the pathogenesis. Sleep-related reduced ventilatory drive and neuromuscular combined with anatomic risk factors are likely to play a significant role in upper airway obstruction during sleep.[1] The anatomic factors that promote pharyngeal narrowing include large neck circumference, soft tissue, bone, or vessels. [6] Many of these structures can lead to increased surrounding pressure of the upper airway resulting in pharyngeal collapsibility and/or insufficient space to accommodate the airflow in a portion of the upper airway during sleep. [7] In addition, the upper airway muscle tone plays a role as when it decreases, a repetitive total or partial airway collapse results. The most common cause of OSA in adults is obesity, male sex, and advancing age. [8] The severity of OSA decreases with age when adjusting for BMI. [9]

Anatomic Factors

Micrognathia, retrognathia
Facial elongation
Mandibular hypoplasia
Adenoid and tonsillar hypertrophy
Inferior displacement of the hyoid

Nonanatomic Risk Factors

Central fat distribution
Obesity
Advanced age
Male gender
Supine sleeping position
Pregnancy[10]

Additional Factors

Alcohol use
Smoking
Use of sedatives and hypnotics

Associated Medical Disorders

Endocrine disorders (e.g., diabetes mellitus, metabolic syndrome, acromegaly, and hypothyroidism)[11][12]
Neurological disorders (e.g., stroke, spinal cord injury, and myasthenia gravis) [13][14]
Prader Willi syndrome[15]
Down Syndrome[16]
Congestive heart failure[17]
Atrial fibrillation [18]
Obesity hypoventilation syndrome (OHS)[19]

These relationships between OSA and various medical disorders are based mainly on observational studies and not necessarily randomized clinical trials.

Epidemiology

Obstructive sleep apnea is a common condition with significant adverse consequences.[20] OSA (using the definition of 5 or more events/ hour) affects almost 1 billion people globally [21], with 425 million adults aged 30-69 years having moderate to severe OSA (15 or more events/h).[22] In the United States, it has been reported that 25-30% of men and 9-17% of women meet the criteria for obstructive sleep apnea.[23][24] Prevalence is higher in Hispanic, Black, and Asian populations. Prevalence also increases with age, and when individuals reach 50 years of age or more, there are as many women as men who develop the disorder. The increasing prevalence of OSA is related to the rising rates of obesity ranging between 14% and 55%.[23] It has been reported that there is a genetic component as some risk factors, including obesity and upper airway soft tissue structure, are genetically inherited.[25]

Pathophysiology

Upper airway obstruction during sleep is often due to negative collapsing pressure during inspiration; however, progressive expiratory narrowing in the retro palatal area plays an important role.[26] The magnitude of upper airway narrowing during sleep is often related to body mass index, indicating that anatomical and neuromuscular factors contribute to airway obstruction.[27] To understand the mechanisms of OSA, it is helpful to use the concept of the pressure-flow relationship through collapsible tubes.[28] Additional information on risk factors is available in the etiology section.

History and Physical

Patients with suspected OSA usually present with excessive daytime sleepiness, loud snoring, gasping, choking, or breathing cessation while sleeping that a bed partner witnessed. Excessive daytime sleepiness is one of the most common symptoms. However, the majority of patients are asymptomatic.[24] Many patients only report daytime fatigue with or without other associated symptoms. Therefore, the distinction between sleepiness and fatigue should be objectively assessed. Epworth Sleepiness Scale (ESS) [29] can be used to quantitatively evaluate the severity of sleepiness. The ESS score ranges from 0 to 24, and more than 9 points indicate the presence of excessive daytime sleepiness and require additional assessment. A fatigue severity scale can also assess the severity of fatigue symptoms.[30] Using both ESS and FSS is usually helpful as sleepiness, and fatigue symptoms could be present concomitantly. Other symptoms vary from morning headaches [31] and self-reported insomnia [32] to nocturia.[33] Symptoms of sleep-onset insomnia and sleep maintenance insomnia were reported most by women.[34]

The STOP-BANG questionnaire is one of the most widely accepted screening tools for OSA.[35]

Snoring: Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?
Tired: Do you often feel tired, fatigued, or sleepy during the daytime?
Observed: Has anyone observed you stop breathing during your sleep?
Blood pressure: Do you have or are you being treated for high blood pressure?
BMI: BMI ≥ 35 kg/m2
Age: age > 50 yrs
Neck circumference: Neck circumference >40 cm
Gender: Gender male

Use STOP-BANG to decide if high probability of moderate-severe disease. High risk if ‘YES’ to ≥ 3 items Low risk if ‘YES’ to < 3 items Items.

Obesity is the most common finding in individuals with OSA. Other physical findings are large neck circumference (17 inches or 43 cm in males and 16 inches or 40.5 cm), crowded oropharynx (Mallampati 3 to 4), retrognathia, micrognathia, tonsilar hypertrophy, low-lying palate, overjet, and a large tongue. However, after adjusting for body weight and neck size, only lateral narrowing is an independent predictor of OSA.[36]

Evaluation

Any adult patient with unexplained daytime or sleep-related symptoms such as excessive sleepiness, fatigue, or unrefreshing sleep should be evaluated for sleep apnea. However, universal screening for OSA is not recommended in asymptomatic patients except for those who are at risk of occupational hazards such as driving or those who are pilots.[37] [38] In addition, due to the high prevalence of OSA and disease burden, patients with specific comorbidities such as refractory atrial fibrillation, resistant hypertension, and a history of stroke can be screened for sleep apnea regardless of symptoms.[39]

Nighttime in-laboratory Level 1 polysomnography (PSG) is the gold standard test for the diagnosis of obstructive sleep apnea. During the test, patients are monitored with EEG leads, pulse oximetry, temperature and pressure sensors to detect nasal and oral airflow, respiratory impedance plethysmography belts around the chest and abdomen to detect motion, an ECG lead, and EMG sensors to detect muscle contraction in the chin, chest, and legs (as depicted in the polygraph).

Scoring respiratory events in adults rely on 4 channels: [40]

Oronasal thermal sensor
Nasal air pressure transducer
Inductance plethysmography (esophageal manometry or pressure catheter may be used instead)
Pulse oximetry

*A snoring monitor is a required channel but is not used in scoring any respiratory events

According to the American Academy of Sleep Medicine (AASM), hypopnea can be defined based on one of two criteria. It can either be a reduction in airflow of at least 30% for more than 10 seconds associated with at least 4% oxygen desaturation (Medicare criteria) or a reduction in airflow of at least 30% for more than 10 seconds associated with at least 3% oxygen desaturation or an arousal from sleep on EEG (Recommended AASM criteria).[41]

Scoring apnea requires both of the following criteria to be met:

A. Drop in the peak signal excursion by ≥90% of pre-event baseline flow
B. Duration of the drop in flow is ≥10 seconds.
- Apneas usually further are classified based on effort (RIP signals):
- Obstructive apnea, if there is increased effort throughout the entire apnea
- Central apnea, if there is no effort throughout the entire apnea

Mixed apnea occurs if there is no effort in the first part and there is an effort in the second part of the apnea (See polygraph).

Home sleep tests (HST) or portable monitoring (PM) have gained popularity due to their relative accessibility and lower cost. PM, however, should be used with specific rules and procedures based on the AASM unattended PM task force guidelines, which outlined the following criteria [42]:

At a minimum, PM must record airflow, respiratory effort, and blood oxygenation.
The airflow, effort, and oximetric biosensors conventionally used for in-laboratory PSG should be used in PM.
PM testing must be performed under the auspices of an AASM-accredited comprehensive sleep medicine program with written policies and procedures.
An experienced sleep technologist/technician must apply the sensors or directly educate patients in sensor application.
The PM device must allow for the display of raw data with the capability of manual scoring or editing of automated scoring by a qualified sleep technician/technologist.
A board-certified sleep specialist, or an individual who fulfills the eligibility criteria for the sleep medicine certification examination, must review the raw data from PM using scoring criteria consistent with current published AASM standards.[41] Under the conditions specified above, PM may be used for unattended studies in the patient's home.
A follow-up visit to review test results should be performed for all patients undergoing PM.
In patients with a high pretest probability of moderate to severe OSA, negative or technically inadequate PM tests should prompt in-laboratory polysomnography.

Unattended PM and HST are appropriate for adults with a high pretest probability for sleep apnea and no significant medical comorbidities (advanced congestive heart failure, chronic obstructive pulmonary disease, and neurologic disorders). These are level III sleep tests consisting of pulse oximetry, heart rate monitoring, temperature and pressure sensors to detect nasal and oral airflow, resistance belts around the chest and abdomen to detect motion, and a sensor to detect body position. Moderate and severe sleep apnea is detected on these tests, but due to the chance of underestimating the apnea-hypopnea index (AHI) relative to the total recording time (which may be longer than the total sleep time measured in an in-lab study), mild sleep apnea may go undiagnosed, and a repeat in-lab study may be needed. A proposed algorithm for the appropriate use of PM and in-lab PSG is outlined in the figure below.

One of the main limitations of HST is that the majority of studies rely on total recording time (TRT) as the denominator instead of total sleep time (TST) in the calculation of AHI as there are no EEG sensors to differentiate sleep from wake. It is estimated that using TRT can result in an underestimation of AHI by at least 20%. [43] In order to differentiate indices of respiratory events generated by HST (without recorded sleep), the AASM recommended the use of the term Respiratory Event Index (REI). Both apnea-hypopnea index and REI are the average number of obstructive events per hour (during sleep or recording time, respectively).

While most PM devices include flow sensors, other technologies use an alternative method without flow such as peripheral arterial tonometry (called PAT) to identify sleep-disordered breathing events. The OSA severity obtained using PAT devices is called pAHI and is reported to provide similar indices to PSG-derived AHI.[44]

The severity of OSA in adults is based on AHI, REI, or pAHI as follows:

Mild: 5 to 15 events per hour
Moderate: >15 to 30 events per hour
Severe: greater than 30 events per hour

The burden of disease in mild OSA is controversial and based on associated clinical sequelae (such as excessive daytime sleepiness, sleep maintenance insomnia, and cognitive dysfunction).[45]

Recent studies challenged however the traditional definition and scoring criteria of OSA in adults due to its limitations in capturing the pathophysiological impact in individual patients.[21] Different metrics have been proposed to increase precision in diagnosing individuals with OSA.[46] These metrics include hypoxic burden, [47] nocturnal heart rate changes, [48] total sleep time with SpO2 <90% (TST90), [49] duration of obstructive events, [50] sleep arousal burden, [51] and even Genetics. [52][53]

Treatment / Management

The treatment of OSA is a multi-pronged approach and should be individualized to each patient. While treatment of moderate to severe OSA has been shown to improve clinical outcomes [54], there is limited or inconsistent evidence about the impact of therapy of mild OSA on neurocognition, mood, vehicle accidents, cardiovascular events, stroke, and arrhythmias.[45]

Lifestyle Changes and Treating Underlying Medical Conditions

The importance of weight loss should be emphasized in OSA patients with overweight and obesity.[55][56] Although weight loss is recommended and can often decrease the severity of obstructive sleep apnea, it is not usually curative. Patients should be educated on the impact of sleep duration and their health and prioritize getting at least 7 to 8 hours of sleep per night. [57] Patients should be counseled to avoid alcohol, benzodiazepines, opiates, and some antidepressants, which may worsen their condition. For all patients, it is important to address any concomitant nasal obstruction with nasal steroids for allergic rhinitis or surgically for nasal valve collapse. For patients with lung or heart disease (such as asthma or heart failure), it is very important to optimize the treatment of these disorders.

Positional Therapy

OSA that is more prominent in the supine position can be treated with a positioning device to keep a patient on their side can be an option. [58][59]

Positive Airway Pressure (PAP) Therapy

Continuous positive airway pressure (PAP) is the most effective treatment for adults.[60] Bilevel PAP (BPAP) is also better tolerated by patients who require higher pressure settings (greater than 15 cm H2O). However, despite the high efficacy of PAP in eliminating respiratory events, its effectiveness is dampened by the decreased use of treatment during sleep and inadequate adherence. Adherence to PAP among patients with OSA remains a great challenge as nearly half of patients do not adequately adhere to treatment after the first month.[61] The American Thoracic Society published a recent statement on PAP adherence tracking systems and the optimal monitoring strategies and outcome measures in adults. [62] It is important to standardize the PAP adherence report not only the number of hours used more than 4 hours per night (>70% of nights) but also the amount of mask leak and residual apnea and hypopnea index. However, what is the optimal goal in adherence to OSA treatment? Recent studies are looking at the utility of telemedicine adherence interventions, remote monitoring of CPAP,[63] and more interactive features with individual patients and their families have shown to increase CPAP adherence rates.[64][65][66]

Several studies have reported conflicting findings when assessing the effect of PAP therapy on cardiovascular outcomes in patients with OSA.[46] In a recent randomized control trial, CPAP use for a minimum of one year in patients with Acute Coronary Syndrome (ACS) and OSA (ISAACC) without excessive daytime sleepiness did not lower the incidence of cardiovascular events (defined as cardiac-related death or one or more of the following outcomes: acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalizations for unstable angina or transient ischaemic attack).[67] The adherence to PAP therapy was low (2.78 h/night), and follow-up was not long enough, which are significant limitations of this study. In another observational cohort study with long-term follow-up, PAP use was associated with lower all-cause mortality among patients with severe OSA around years 6–7 of follow-up.[68] In a more recent study, patients with coronary artery disease and OSA without excessive sleepiness who exhibited higher changes in heart rate benefited more from CPAP therapy.[69]

Oral Appliance

For patients unable or unwilling to use CPAP or those who will be unable to access electricity reliably, custom-fitted and titrated oral appliances or mandibular advancements devices (MAD) can be used to bring the lower jaw forward and relieve airway obstruction (See picture). This typically works best for candidates with appropriate dentition and mild to moderate sleep apnea. In a randomized clinical trial on 126 patients with moderate-severe OSA,[70] 24-hour mean arterial pressure was similar between CPAP and MAD after 1-month of therapy. MAD was superior to CPAP for improving quality of life measures. More recently, another RCT demonstrated similar long-term improvement in self-reported neurobehavioral outcomes during a 10-year follow-up.[71] The American Academy of Sleep Medicine (AASM) and the American Academy of Dental Sleep Medicine (AADSM) developed guidelines for using MAD in patients with OSA.[72] The AASM/AADSM guidelines recommend the following:

Oral appliances can be considered rather than no treatment for adult patients with snoring (without OSA) or those with OSA who do not tolerate CPAP therapy or prefer alternate treatment.
When a sleep physician prescribes oral appliance therapy for an adult patient with obstructive sleep apnea.
A qualified dentist should use a custom, titratable appliance.
A follow-up with a qualified dentist after oral appliance therapy is initiated in adult patients with OSA to assess for dental-related side effects.
A follow-up with sleep testing to confirm treatment efficacy.

Surgical Treatments

Uvulopalatopharyngoplasty (UPPP) surgically removes the uvula and tissue from the soft palate to create more space in the oropharynx.[73] This is sometimes done in conjunction with a tonsillectomy and adenoidectomy. Nevertheless, the long-term efficacy of UPPP is very limited, with less than 50% of patients having a significant increase in AHI after the first year.[74]

Maxillomandibular advancement (MMA) requires both the upper and lower jaws to be detached and surgically advanced anteriorly to increase space in the oropharynx.[75] This is best for patients with retrognathia and is less successful in older patients or those with larger neck circumferences. More recently, drug-induced sleep endoscopy (DISE) has been used for preoperative planning to identify multiple levels of obstruction in these patients and candidacy for surgical treatment such as MMA and hypoglossal nerve stimulator.[76] This allows surgeons to address any nasal, soft palate, and hypopharyngeal obstructions that may be present during a single surgery.[77]

A newer option is the implantable hypoglossal nerve stimulator (HNS), usually unilateral, although bilateral implantation has been recently reported.[78] It works by stimulating the genioglossus (upper airway dilator muscle) during apneas resulting in tongue protrusion and relief of the obstruction.[79] HNS effectively reduces AHI (median AHI score at 12 months decreased by 68%, from 29.3 events per hour to 9.0 events per hour) and improves sleepiness symptoms in those with moderate to severe OSA that is not tolerating PAP treatment.[80] Adverse events reported short- and long-term following HNS is not very common. In one study, 134 adverse events were reported from 132 patient reports over five years.[81] The most common adverse events reported after HNS are tongue abrasion (11.0%), pain (6.2%), and device malfunction (3-6%).[79]

The eligibility criteria for HNS adopted from the original randomized trial include the following characteristics:[80]

Adults >18 years of age
Moderate to severe OSA (AHI between 20 to 50 with less than 25% central or mixed apneas)
Inability to tolerate CPAP
No complete concentric collapse at the palate on drug-induced sleep endoscopy

Exclusion criteria for HNS include the following:

BMI > 32.0 kg/m2.
Neuromuscular disease.
Hypoglossal-nerve palsy.
Severe restrictive or obstructive pulmonary disease.
Moderate-to-severe pulmonary arterial hypertension.
Severe valvular heart disease.
Heart failure, New York Heart Association class III or IV.
Recent myocardial infarction or severe cardiac arrhythmias (within the past 6 months).
Persistent uncontrolled hypertension despite medication use.
Active psychiatric disease and coexisting nonrespiratory sleep disorders.

In extreme cases, OSA can also be treated with a tracheostomy to bypass the oropharyngeal obstruction. This management option is also best addressed at academic or specialty sleep centers that are experienced in treating patients with tracheostomy. Such patients will encounter numerous challenges with home care, durable medical equipment, and family/partner education on tracheostomy management. Many patients with severe OSA requiring tracheostomy have comorbidities.

Differential Diagnosis

Asthma
Central sleep apnea
Chronic obstructive pulmonary disease
Depression
Gastroesophageal reflux
Hypothyroidism
Narcolepsy
Periodic limb movement disorder

Prognosis

The short-term prognosis of OSA with treatment is good, but the long-term prognosis is guarded. The biggest problem is the lack of adherence to CPAP, as nearly 50% of patients stop using CPAP within the first month despite education.[82] Many patients have comorbidities and /or are at risk for adverse cardiac events and stroke. Hence those who do not use CPAP are at increased risk of cardiac and cerebral adverse events [83] in addition to higher annual healthcare-related expenses. [84] Further, OSA is also associated with pulmonary hypertension, hypercapnia, hypoxemia, and daytime sedation. In addition, these individuals have a high risk of motor vehicle accidents. The overall life expectancy of patients with OSA is lower than the general population. OSA is known to affect cardiac function, particularly in obese individuals. [85][86] CPAP treatment was recently found to improve left ventricular (LV) and right ventricular (RV) mechanics in patients with OSA. [87]

Complications

Hypertension
Myocardial infarction
Cerebrovascular accident
Depression
Sleeplessness related accidents

Deterrence and Patient Education

Weight loss should be encouraged in patients with OSA. They should be counseled to avoid alcohol, benzodiazepines, opiates, and some antidepressants, which may worsen their condition. Additionally, they should be made aware of the importance of proper sleep hygiene, getting enough sleep every night, and the risks of driving while sleepy. Adherence to CPAP use should be encouraged as well as how to clean and maintain the machine properly.

Enhancing Healthcare Team Outcomes

The management of patients with OSA is best accomplished with an interprofessional team that includes a sleep specialist, primary provider, cardiologist, otolaryngologist, dietitian, pulmonologist, and neurologist. There are many options to treat OSA, the primary one being CPAP. Unfortunately, compliance with CPAP remains low. Some patients may benefit from an oral or nasal device, but compliance remains an issue. Surgery is the last step and should only be considered after a thorough patient evaluation. Surgery does not cure the disorder, is expensive, and can be associated with severe complications. The prognosis for most patients with OSA is guarded. Until the patient starts to lose weight, most therapies have poor efficacy.

(Click Image to Enlarge)

A polygraph depicting example of central and obstructive apnea.
Contributed by Abdulghani Sankari, MD

(Click Image to Enlarge)

A polygraph recording during sleep. The panel shows electroencephalogram (EEG), Electrooculogram (EOG), electrocardiogram (ECG), in addition to chin electromyogram (EMG) signals from the lower limbs and respiratory signals (C flow), chest and abdomen respiratory plethysmography (RIP) and O2 saturation (SaO2) during 30 seconds window (Epoch).
Contributed by Abdulghani Sankari, MD, PhD

(Click Image to Enlarge)

A polygraph recording during sleep. The panel shows electroencephalogram (EEG), Electrooculogram (EOG), electrocardiogram (ECG), in addition to chin electromyogram (EMG) during 120 seconds window. Note the repetitive obstructive apnea (OA) with persistent effort during cessation of both flow channels [nasal pressure flow (P-flow) and thermester ( T-flow)] followed by desaturation (light blue arrows) ad arousals (dark blue arrows).
Contributed by Abdulghani Sankari, MD, PhD

(Click Image to Enlarge)

Clinical assessment of patients with suspected sleep apnea.
Contributed by Abdulghani Sankari, MD, PhD

(Click Image to Enlarge)

The available types of sleep apnea testing from level I (in-lab PSG) to portable monitoring devices (level II, III and IV). Note that only level II and III are acceptable for testing of OSA by the AASM guidelines.
Contributed by Abdulghani Sankari, MD, PhD

Details

References

[1]

Sankri-Tarbichi AG. Obstructive sleep apnea-hypopnea syndrome: Etiology and diagnosis. Avicenna journal of medicine. 2012 Jan:2(1):3-8. doi: 10.4103/2231-0770.94803. Epub [PubMed PMID: 23210013]

[2]

Mehrtash M, Bakker JP, Ayas N. Predictors of Continuous Positive Airway Pressure Adherence in Patients with Obstructive Sleep Apnea. Lung. 2019 Apr:197(2):115-121. doi: 10.1007/s00408-018-00193-1. Epub 2019 Jan 7 [PubMed PMID: 30617618]

[3]

Esteller E, Carrasco M, Díaz-Herrera MÁ, Vila J, Sampol G, Juvanteny J, Sieira R, Farré A, Vilaseca I. Clinical Practice Guideline recommendations on examination of the upper airway for adults with suspected obstructive sleep apnoea-hypopnoea syndrome. Acta otorrinolaringologica espanola. 2019 Nov-Dec:70(6):364-372. doi: 10.1016/j.otorri.2018.06.008. Epub 2019 Jan 5 [PubMed PMID: 30616837]

Level 1 (high-level) evidence

[4]

Carneiro-Barrera A, Díaz-Román A, Guillén-Riquelme A, Buela-Casal G. Weight loss and lifestyle interventions for obstructive sleep apnoea in adults: Systematic review and meta-analysis. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019 May:20(5):750-762. doi: 10.1111/obr.12824. Epub 2019 Jan 4 [PubMed PMID: 30609450]

Level 1 (high-level) evidence

[5]

Yeghiazarians Y, Jneid H, Tietjens JR, Redline S, Brown DL, El-Sherif N, Mehra R, Bozkurt B, Ndumele CE, Somers VK. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021 Jul 20:144(3):e56-e67. doi: 10.1161/CIR.0000000000000988. Epub 2021 Jun 21 [PubMed PMID: 34148375]

[6]

Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. American journal of respiratory and critical care medicine. 1995 Nov:152(5 Pt 1):1673-89 [PubMed PMID: 7582313]

[7]

Isono S, Remmers JE, Tanaka A, Sho Y, Sato J, Nishino T. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. Journal of applied physiology (Bethesda, Md. : 1985). 1997 Apr:82(4):1319-26 [PubMed PMID: 9104871]

[8]

Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep medicine. 2010 May:11(5):441-6. doi: 10.1016/j.sleep.2009.10.005. Epub 2010 Apr 1 [PubMed PMID: 20362502]

[9]

Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. Prevalence and severity. American journal of respiratory and critical care medicine. 1998 Jan:157(1):144-8 [PubMed PMID: 9445292]

[10]

Dominguez JE, Habib AS. Obstructive sleep apnea in pregnant women. International anesthesiology clinics. 2022 Apr 1:60(2):59-65. doi: 10.1097/AIA.0000000000000360. Epub [PubMed PMID: 35261345]

[11]

Reutrakul S, Mokhlesi B. Obstructive Sleep Apnea and Diabetes: A State of the Art Review. Chest. 2017 Nov:152(5):1070-1086. doi: 10.1016/j.chest.2017.05.009. Epub 2017 May 17 [PubMed PMID: 28527878]

[12]

Akset M, Poppe KG, Kleynen P, Bold I, Bruyneel M. Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationship. Clinical endocrinology. 2023 Jan:98(1):3-13. doi: 10.1111/cen.14685. Epub 2022 Feb 19 [PubMed PMID: 35182448]

[13]

Yaggi H, Mohsenin V. Obstructive sleep apnoea and stroke. The Lancet. Neurology. 2004 Jun:3(6):333-42 [PubMed PMID: 15157848]

[14]

Sankari A, Bascom A, Oomman S, Badr MS. Sleep disordered breathing in chronic spinal cord injury. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2014 Jan 15:10(1):65-72. doi: 10.5664/jcsm.3362. Epub 2014 Jan 15 [PubMed PMID: 24426822]

[15]

Kim SJ, Cho SY, Jin DK. Prader-Willi syndrome: an update on obesity and endocrine problems. Annals of pediatric endocrinology & metabolism. 2021 Dec:26(4):227-236. doi: 10.6065/apem.2142164.082. Epub 2021 Dec 31 [PubMed PMID: 34991300]

[16]

Hyzer JM, Milczuk HA, Macarthur CJ, King EF, Quintanilla-Dieck L, Lam DJ. Drug-Induced Sleep Endoscopy Findings in Children With Obstructive Sleep Apnea With vs Without Obesity or Down Syndrome. JAMA otolaryngology-- head & neck surgery. 2021 Feb 1:147(2):175-181. doi: 10.1001/jamaoto.2020.4548. Epub [PubMed PMID: 33270102]

[17]

Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. American journal of respiratory and critical care medicine. 1999 Oct:160(4):1101-6 [PubMed PMID: 10508793]

[18]

Moula AI, Parrini I, Tetta C, Lucà F, Parise G, Rao CM, Mauro E, Parise O, Matteucci F, Gulizia MM, La Meir M, Gelsomino S. Obstructive Sleep Apnea and Atrial Fibrillation. Journal of clinical medicine. 2022 Feb 25:11(5):. doi: 10.3390/jcm11051242. Epub 2022 Feb 25 [PubMed PMID: 35268335]

[20]

Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. The New England journal of medicine. 1993 Apr 29:328(17):1230-5 [PubMed PMID: 8464434]

[21]

Malhotra A, Ayappa I, Ayas N, Collop N, Kirsch D, Mcardle N, Mehra R, Pack AI, Punjabi N, White DP, Gottlieb DJ. Metrics of sleep apnea severity: beyond the apnea-hypopnea index. Sleep. 2021 Jul 9:44(7):. doi: 10.1093/sleep/zsab030. Epub [PubMed PMID: 33693939]

[22]

Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pépin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. The Lancet. Respiratory medicine. 2019 Aug:7(8):687-698. doi: 10.1016/S2213-2600(19)30198-5. Epub 2019 Jul 9 [PubMed PMID: 31300334]

[23]

Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. American journal of epidemiology. 2013 May 1:177(9):1006-14. doi: 10.1093/aje/kws342. Epub 2013 Apr 14 [PubMed PMID: 23589584]

[23]

Antoine MH, Sankari A, Bollu PC. Obesity-Hypoventilation Syndrome. StatPearls. 2023 Jan:(): [PubMed PMID: 29493925]

[24]

Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020 Apr 14:323(14):1389-1400. doi: 10.1001/jama.2020.3514. Epub [PubMed PMID: 32286648]

[25]

Garvey JF, Pengo MF, Drakatos P, Kent BD. Epidemiological aspects of obstructive sleep apnea. Journal of thoracic disease. 2015 May:7(5):920-9. doi: 10.3978/j.issn.2072-1439.2015.04.52. Epub [PubMed PMID: 26101650]

Level 2 (mid-level) evidence

[26]

Morrell MJ, Arabi Y, Zahn B, Badr MS. Progressive retropalatal narrowing preceding obstructive apnea. American journal of respiratory and critical care medicine. 1998 Dec:158(6):1974-81 [PubMed PMID: 9847295]

[27]

Sankri-Tarbichi AG, Rowley JA, Badr MS. Expiratory pharyngeal narrowing during central hypocapnic hypopnea. American journal of respiratory and critical care medicine. 2009 Feb 15:179(4):313-9. doi: 10.1164/rccm.200805-741OC. Epub 2008 Nov 21 [PubMed PMID: 19201929]

[28]

Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S. Upper airway pressure-flow relationships in obstructive sleep apnea. Journal of applied physiology (Bethesda, Md. : 1985). 1988 Feb:64(2):789-95 [PubMed PMID: 3372436]

[29]

Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec:14(6):540-5 [PubMed PMID: 1798888]

[30]

Learmonth YC, Dlugonski D, Pilutti LA, Sandroff BM, Klaren R, Motl RW. Psychometric properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale. Journal of the neurological sciences. 2013 Aug 15:331(1-2):102-7. doi: 10.1016/j.jns.2013.05.023. Epub 2013 Jun 20 [PubMed PMID: 23791482]

[31]

Russell MB, Kristiansen HA, Kværner KJ. Headache in sleep apnea syndrome: epidemiology and pathophysiology. Cephalalgia : an international journal of headache. 2014 Sep:34(10):752-5. doi: 10.1177/0333102414538551. Epub 2014 Jun 13 [PubMed PMID: 24928423]

[32]

Cho YW, Kim KT, Moon HJ, Korostyshevskiy VR, Motamedi GK, Yang KI. Comorbid Insomnia With Obstructive Sleep Apnea: Clinical Characteristics and Risk Factors. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2018 Mar 15:14(3):409-417. doi: 10.5664/jcsm.6988. Epub 2018 Mar 15 [PubMed PMID: 29458695]

[33]

Maeda T, Fukunaga K, Nagata H, Haraguchi M, Kikuchi E, Miyajima A, Yamasawa W, Shirahama R, Narita M, Betsuyaku T, Asano K, Oya M. Obstructive sleep apnea syndrome should be considered as a cause of nocturia in younger patients without other voiding symptoms. Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 2016 Jul-Aug:10(7-8):E241-E245. doi: 10.5489/cuaj.3508. Epub 2016 Jul 12 [PubMed PMID: 28255415]

[34]

Subramanian S, Guntupalli B, Murugan T, Bopparaju S, Chanamolu S, Casturi L, Surani S. Gender and ethnic differences in prevalence of self-reported insomnia among patients with obstructive sleep apnea. Sleep & breathing = Schlaf & Atmung. 2011 Dec:15(4):711-5. doi: 10.1007/s11325-010-0426-4. Epub 2010 Oct 16 [PubMed PMID: 20953842]

[35]

Nagappa M, Liao P, Wong J, Auckley D, Ramachandran SK, Memtsoudis S, Mokhlesi B, Chung F. Validation of the STOP-Bang Questionnaire as a Screening Tool for Obstructive Sleep Apnea among Different Populations: A Systematic Review and Meta-Analysis. PloS one. 2015:10(12):e0143697. doi: 10.1371/journal.pone.0143697. Epub 2015 Dec 14 [PubMed PMID: 26658438]

Level 1 (high-level) evidence

[36]

Schellenberg JB, Maislin G, Schwab RJ. Physical findings and the risk for obstructive sleep apnea. The importance of oropharyngeal structures. American journal of respiratory and critical care medicine. 2000 Aug:162(2 Pt 1):740-8 [PubMed PMID: 10934114]

[37]

Jonas DE, Amick HR, Feltner C, Weber RP, Arvanitis M, Stine A, Lux L, Harris RP. Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2017 Jan 24:317(4):415-433. doi: 10.1001/jama.2016.19635. Epub [PubMed PMID: 28118460]

Level 1 (high-level) evidence

[38]

Colvin LJ, Collop NA. Commercial Motor Vehicle Driver Obstructive Sleep Apnea Screening and Treatment in the United States: An Update and Recommendation Overview. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2016 Jan:12(1):113-25. doi: 10.5664/jcsm.5408. Epub [PubMed PMID: 26094916]

Level 3 (low-level) evidence

[39]

Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004 Apr 28:291(16):2013-6 [PubMed PMID: 15113821]

[40]

Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, Marcus CL, Mehra R, Parthasarathy S, Quan SF, Redline S, Strohl KP, Davidson Ward SL, Tangredi MM, American Academy of Sleep Medicine. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2012 Oct 15:8(5):597-619. doi: 10.5664/jcsm.2172. Epub 2012 Oct 15 [PubMed PMID: 23066376]

[41]

Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, Troester MT, Vaughn BV. AASM Scoring Manual Updates for 2017 (Version 2.4). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2017 May 15:13(5):665-666. doi: 10.5664/jcsm.6576. Epub 2017 May 15 [PubMed PMID: 28416048]

[42]

Collop NA, Anderson WM, Boehlecke B, Claman D, Goldberg R, Gottlieb DJ, Hudgel D, Sateia M, Schwab R, Portable Monitoring Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2007 Dec 15:3(7):737-47 [PubMed PMID: 18198809]

[43]

Light MP, Casimire TN, Chua C, Koushyk V, Burschtin OE, Ayappa I, Rapoport DM. Addition of frontal EEG to adult home sleep apnea testing: does a more accurate determination of sleep time make a difference? Sleep & breathing = Schlaf & Atmung. 2018 Dec:22(4):1179-1188. doi: 10.1007/s11325-018-1735-2. Epub 2018 Oct 11 [PubMed PMID: 30311183]

[44]

Hedner J, White DP, Malhotra A, Herscovici S, Pittman SD, Zou D, Grote L, Pillar G. Sleep staging based on autonomic signals: a multi-center validation study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2011 Jun 15:7(3):301-6. doi: 10.5664/JCSM.1078. Epub [PubMed PMID: 21677901]

Level 1 (high-level) evidence

[45]

Chowdhuri S, Quan SF, Almeida F, Ayappa I, Batool-Anwar S, Budhiraja R, Cruse PE, Drager LF, Griss B, Marshall N, Patel SR, Patil S, Knight SL, Rowley JA, Slyman A, ATS Ad Hoc Committee on Mild Obstructive Sleep Apnea. An Official American Thoracic Society Research Statement: Impact of Mild Obstructive Sleep Apnea in Adults. American journal of respiratory and critical care medicine. 2016 May 1:193(9):e37-54. doi: 10.1164/rccm.201602-0361ST. Epub [PubMed PMID: 27128710]

[46]

Yasir M, Pervaiz A, Sankari A. Cardiovascular Outcomes in Sleep-Disordered Breathing: Are We Under-estimating? Frontiers in neurology. 2022:13():801167. doi: 10.3389/fneur.2022.801167. Epub 2022 Mar 15 [PubMed PMID: 35370882]

[47]

Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. European heart journal. 2019 Apr 7:40(14):1149-1157. doi: 10.1093/eurheartj/ehy624. Epub [PubMed PMID: 30376054]

[48]

Sankari A, Ravelo LA, Maresh S, Aljundi N, Alsabri B, Fawaz S, Hamdon M, Al-Kubaisi G, Hagen E, Badr MS, Peppard P. Longitudinal effect of nocturnal R-R intervals changes on cardiovascular outcome in a community-based cohort. BMJ open. 2019 Jul 17:9(7):e030559. doi: 10.1136/bmjopen-2019-030559. Epub 2019 Jul 17 [PubMed PMID: 31315880]

[49]

Oldenburg O, Wellmann B, Buchholz A, Bitter T, Fox H, Thiem U, Horstkotte D, Wegscheider K. Nocturnal hypoxaemia is associated with increased mortality in stable heart failure patients. European heart journal. 2016 Jun 1:37(21):1695-703. doi: 10.1093/eurheartj/ehv624. Epub 2015 Nov 26 [PubMed PMID: 26612581]

[50]

Butler MP, Emch JT, Rueschman M, Sands SA, Shea SA, Wellman A, Redline S. Apnea-Hypopnea Event Duration Predicts Mortality in Men and Women in the Sleep Heart Health Study. American journal of respiratory and critical care medicine. 2019 Apr 1:199(7):903-912. doi: 10.1164/rccm.201804-0758OC. Epub [PubMed PMID: 30336691]

[51]

Shahrbabaki SS, Linz D, Hartmann S, Redline S, Baumert M. Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women. European heart journal. 2021 Jun 1:42(21):2088-2099. doi: 10.1093/eurheartj/ehab151. Epub [PubMed PMID: 33876221]

[52]

Khalyfa A, Zhang C, Khalyfa AA, Foster GE, Beaudin AE, Andrade J, Hanly PJ, Poulin MJ, Gozal D. Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults. Sleep. 2016 Dec 1:39(12):2077-2090. doi: 10.5665/sleep.6302. Epub 2016 Dec 1 [PubMed PMID: 27634792]

[53]

Li K, Wei P, Qin Y, Wei Y. MicroRNA expression profiling and bioinformatics analysis of dysregulated microRNAs in obstructive sleep apnea patients. Medicine. 2017 Aug:96(34):e7917. doi: 10.1097/MD.0000000000007917. Epub [PubMed PMID: 28834917]

Level 2 (mid-level) evidence

[54]

da Silva Paulitsch F, Zhang L. Continuous positive airway pressure for adults with obstructive sleep apnea and cardiovascular disease: a meta-analysis of randomized trials. Sleep medicine. 2019 Feb:54():28-34. doi: 10.1016/j.sleep.2018.09.030. Epub 2018 Oct 30 [PubMed PMID: 30529774]

Level 1 (high-level) evidence

[55]

Ng SSS, Tam WWS, Lee RWW, Chan TO, Yiu K, Yuen BTY, Wong KT, Woo J, Ma RCW, Chan KKP, Ko FWS, Cistulli PA, Hui DS. Effect of Weight Loss and Continuous Positive Airway Pressure on Obstructive Sleep Apnea and Metabolic Profile Stratified by Craniofacial Phenotype: A Randomized Clinical Trial. American journal of respiratory and critical care medicine. 2022 Mar 15:205(6):711-720. doi: 10.1164/rccm.202106-1401OC. Epub [PubMed PMID: 34936531]

Level 1 (high-level) evidence

[56]

Wong AM, Barnes HN, Joosten SA, Landry SA, Dabscheck E, Mansfield DR, Dharmage SC, Senaratna CV, Edwards BA, Hamilton GS. The effect of surgical weight loss on obstructive sleep apnoea: A systematic review and meta-analysis. Sleep medicine reviews. 2018 Dec:42():85-99. doi: 10.1016/j.smrv.2018.06.001. Epub 2018 Jun 19 [PubMed PMID: 30001806]

Level 1 (high-level) evidence

[57]

Al Lawati NM, Patel SR, Ayas NT. Epidemiology, risk factors, and consequences of obstructive sleep apnea and short sleep duration. Progress in cardiovascular diseases. 2009 Jan-Feb:51(4):285-93. doi: 10.1016/j.pcad.2008.08.001. Epub [PubMed PMID: 19110130]

[58]

Cerritelli L, Caranti A, Migliorelli A, Bianchi G, Stringa LM, Bonsembiante A, Cammaroto G, Pelucchi S, Vicini C. Sleep position and obstructive sleep apnea (OSA): Do we know how we sleep? A new explorative sleeping questionnaire. Sleep & breathing = Schlaf & Atmung. 2022 Dec:26(4):1973-1981. doi: 10.1007/s11325-022-02576-4. Epub 2022 Feb 7 [PubMed PMID: 35129756]

[59]

Jo JH, Kim SH, Jang JH, Park JW, Chung JW. Comparison of polysomnographic and cephalometric parameters based on positional and rapid eye movement sleep dependency in obstructive sleep apnea. Scientific reports. 2022 Jun 14:12(1):9828. doi: 10.1038/s41598-022-13850-6. Epub 2022 Jun 14 [PubMed PMID: 35701572]

[60]

Ravesloot MJ, de Vries N. Reliable calculation of the efficacy of non-surgical and surgical treatment of obstructive sleep apnea revisited. Sleep. 2011 Jan 1:34(1):105-10 [PubMed PMID: 21203364]

[61]

Xanthopoulos MS, Kim JY, Blechner M, Chang MY, Menello MK, Brown C, Matthews E, Weaver TE, Shults J, Marcus CL. Self-Efficacy and Short-Term Adherence to Continuous Positive Airway Pressure Treatment in Children. Sleep. 2017 Jul 1:40(7):. doi: 10.1093/sleep/zsx096. Epub [PubMed PMID: 28541508]

[62]

Schwab RJ, Badr SM, Epstein LJ, Gay PC, Gozal D, Kohler M, Lévy P, Malhotra A, Phillips BA, Rosen IM, Strohl KP, Strollo PJ, Weaver EM, Weaver TE, ATS Subcommittee on CPAP Adherence Tracking Systems. An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults. American journal of respiratory and critical care medicine. 2013 Sep 1:188(5):613-20. doi: 10.1164/rccm.201307-1282ST. Epub [PubMed PMID: 23992588]

[63]

Fox N, Hirsch-Allen AJ, Goodfellow E, Wenner J, Fleetham J, Ryan CF, Kwiatkowska M, Ayas NT. The impact of a telemedicine monitoring system on positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial. Sleep. 2012 Apr 1:35(4):477-81. doi: 10.5665/sleep.1728. Epub 2012 Apr 1 [PubMed PMID: 22467985]

Level 1 (high-level) evidence

[64]

Bakker JP, Weaver TE, Parthasarathy S, Aloia MS. Adherence to CPAP: What Should We Be Aiming For, and How Can We Get There? Chest. 2019 Jun:155(6):1272-1287. doi: 10.1016/j.chest.2019.01.012. Epub 2019 Jan 23 [PubMed PMID: 30684472]

[65]

Khan NNS, Todem D, Bottu S, Badr MS, Olomu A. Impact of patient and family engagement in improving continuous positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022 Jan 1:18(1):181-191. doi: 10.5664/jcsm.9534. Epub [PubMed PMID: 34270409]

Level 1 (high-level) evidence

[66]

Thong BKS, Loh GXY, Lim JJ, Lee CJL, Ting SN, Li HP, Li QY. Telehealth Technology Application in Enhancing Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea Patients: A Review of Current Evidence. Frontiers in medicine. 2022:9():877765. doi: 10.3389/fmed.2022.877765. Epub 2022 May 3 [PubMed PMID: 35592853]

[67]

Sánchez-de-la-Torre M, Sánchez-de-la-Torre A, Bertran S, Abad J, Duran-Cantolla J, Cabriada V, Mediano O, Masdeu MJ, Alonso ML, Masa JF, Barceló A, de la Peña M, Mayos M, Coloma R, Montserrat JM, Chiner E, Perelló S, Rubinós G, Mínguez O, Pascual L, Cortijo A, Martínez D, Aldomà A, Dalmases M, McEvoy RD, Barbé F, Spanish Sleep Network. Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial. The Lancet. Respiratory medicine. 2020 Apr:8(4):359-367. doi: 10.1016/S2213-2600(19)30271-1. Epub 2019 Dec 12 [PubMed PMID: 31839558]

Level 1 (high-level) evidence

[68]

Lisan Q, Van Sloten T, Marques Vidal P, Haba Rubio J, Heinzer R, Empana JP. Association of Positive Airway Pressure Prescription With Mortality in Patients With Obesity and Severe Obstructive Sleep Apnea: The Sleep Heart Health Study. JAMA otolaryngology-- head & neck surgery. 2019 Jun 1:145(6):509-515. doi: 10.1001/jamaoto.2019.0281. Epub [PubMed PMID: 30973594]

[69]

Azarbarzin A, Zinchuk A, Wellman A, Labarca G, Vena D, Gell L, Messineo L, White DP, Gottlieb DJ, Redline S, Peker Y, Sands SA. Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness. American journal of respiratory and critical care medicine. 2022 Sep 15:206(6):767-774. doi: 10.1164/rccm.202111-2608OC. Epub [PubMed PMID: 35579605]

[70]

Phillips CL, Grunstein RR, Darendeliler MA, Mihailidou AS, Srinivasan VK, Yee BJ, Marks GB, Cistulli PA. Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. American journal of respiratory and critical care medicine. 2013 Apr 15:187(8):879-87. doi: 10.1164/rccm.201212-2223OC. Epub [PubMed PMID: 23413266]

Level 1 (high-level) evidence

[71]

Uniken Venema JAM, Doff MHJ, Joffe-Sokolova D, Wijkstra PJ, van der Hoeven JH, Stegenga B, Hoekema A. Long-term obstructive sleep apnea therapy: a 10-year follow-up of mandibular advancement device and continuous positive airway pressure. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2020 Mar 15:16(3):353-359. doi: 10.5664/jcsm.8204. Epub 2020 Jan 14 [PubMed PMID: 31992403]

[72]

Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, Chervin RD. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2015 Jul 15:11(7):773-827. doi: 10.5664/jcsm.4858. Epub 2015 Jul 15 [PubMed PMID: 26094920]

Level 1 (high-level) evidence

[73]

Maniaci A, Di Luca M, Lechien JR, Iannella G, Grillo C, Grillo CM, Merlino F, Calvo-Henriquez C, De Vito A, Magliulo G, Pace A, Vicini C, Cocuzza S, Bannò V, Pollicina I, Stilo G, Bianchi A, La Mantia I. Lateral pharyngoplasty vs. traditional uvulopalatopharyngoplasty for patients with OSA: systematic review and meta-analysis. Sleep & breathing = Schlaf & Atmung. 2022 Dec:26(4):1539-1550. doi: 10.1007/s11325-021-02520-y. Epub 2022 Jan 3 [PubMed PMID: 34978022]

Level 1 (high-level) evidence

[74]

He M, Yin G, Zhan S, Xu J, Cao X, Li J, Ye J. Long-term Efficacy of Uvulopalatopharyngoplasty among Adult Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2019 Sep:161(3):401-411. doi: 10.1177/0194599819840356. Epub 2019 Jun 11 [PubMed PMID: 31184261]

Level 1 (high-level) evidence

[75]

Martin MJ, Khanna A, Srinivasan D, Sovani MP. Patient-reported outcome measures following maxillomandibular advancement surgery in patients with obstructive sleep apnoea syndrome. The British journal of oral & maxillofacial surgery. 2022 Sep:60(7):963-968. doi: 10.1016/j.bjoms.2022.03.006. Epub 2022 Mar 22 [PubMed PMID: 35667944]

[76]

Zhou N, Ho JTF, de Vries N, Bosschieter PFN, Ravesloot MJL, de Lange J. Evaluation of drug-induced sleep endoscopy as a tool for selecting patients with obstructive sleep apnea for maxillomandibular advancement. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022 Apr 1:18(4):1073-1081. doi: 10.5664/jcsm.9802. Epub [PubMed PMID: 34877928]

[77]

Huang Z, Bosschieter PFN, Aarab G, van Selms MKA, Vanhommerig JW, Hilgevoord AAJ, Lobbezoo F, de Vries N. Predicting upper airway collapse sites found in drug-induced sleep endoscopy from clinical data and snoring sounds in patients with obstructive sleep apnea: a prospective clinical study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022 Sep 1:18(9):2119-2131. doi: 10.5664/jcsm.9998. Epub [PubMed PMID: 35459443]

[78]

Lewis R, Pételle B, Campbell MC, MacKay S, Palme C, Raux G, Sommer JU, Maurer JT. Implantation of the nyxoah bilateral hypoglossal nerve stimulator for obstructive sleep apnea. Laryngoscope investigative otolaryngology. 2019 Dec:4(6):703-707. doi: 10.1002/lio2.312. Epub 2019 Nov 22 [PubMed PMID: 31890891]

[79]

Kompelli AR, Ni JS, Nguyen SA, Lentsch EJ, Neskey DM, Meyer TA. The outcomes of hypoglossal nerve stimulation in the management of OSA: A systematic review and meta-analysis. World journal of otorhinolaryngology - head and neck surgery. 2019 Mar:5(1):41-48. doi: 10.1016/j.wjorl.2018.04.006. Epub 2018 Sep 25 [PubMed PMID: 30775701]

Level 1 (high-level) evidence

[80]

Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, Woodson BT, Van de Heyning PH, Goetting MG, Vanderveken OM, Feldman N, Knaack L, Strohl KP, STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. The New England journal of medicine. 2014 Jan 9:370(2):139-49. doi: 10.1056/NEJMoa1308659. Epub [PubMed PMID: 24401051]

[81]

Bellamkonda N, Shiba T, Mendelsohn AH. Adverse Events in Hypoglossal Nerve Stimulator Implantation: 5-Year Analysis of the FDA MAUDE Database. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2021 Feb:164(2):443-447. doi: 10.1177/0194599820960069. Epub 2020 Sep 22 [PubMed PMID: 32957866]

[82]

Guralnick AS, Balachandran JS, Szutenbach S, Adley K, Emami L, Mohammadi M, Farnan JM, Arora VM, Mokhlesi B. Educational video to improve CPAP use in patients with obstructive sleep apnoea at risk for poor adherence: a randomised controlled trial. Thorax. 2017 Dec:72(12):1132-1139. doi: 10.1136/thoraxjnl-2017-210106. Epub 2017 Jun 30 [PubMed PMID: 28667231]

Level 1 (high-level) evidence

[83]

Marshall NS, Wong KK, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2014 Apr 15:10(4):355-62. doi: 10.5664/jcsm.3600. Epub 2014 Apr 15 [PubMed PMID: 24733978]

[84]

Bock JM, Needham KA, Gregory DA, Ekono MM, Wickwire EM, Somers VK, Lerman A. Continuous Positive Airway Pressure Adherence and Treatment Cost in Patients With Obstructive Sleep Apnea and Cardiovascular Disease. Mayo Clinic proceedings. Innovations, quality & outcomes. 2022 Apr:6(2):166-175. doi: 10.1016/j.mayocpiqo.2022.01.002. Epub 2022 Apr 4 [PubMed PMID: 35399584]

Level 2 (mid-level) evidence

[85]

Alkatib S, Sankri-Tarbichi AG, Badr MS. The impact of obesity on cardiac dysfunction in patients with sleep-disordered breathing. Sleep & breathing = Schlaf & Atmung. 2014 Mar:18(1):137-42. doi: 10.1007/s11325-013-0861-0. Epub 2013 May 15 [PubMed PMID: 23673872]

[86]

Saeed S, Romarheim A, Solheim E, Bjorvatn B, Lehmann S. Cardiovascular remodeling in obstructive sleep apnea: focus on arterial stiffness, left ventricular geometry and atrial fibrillation. Expert review of cardiovascular therapy. 2022 Jun:20(6):455-464. doi: 10.1080/14779072.2022.2081547. Epub 2022 Jun 8 [PubMed PMID: 35673889]

[87]

Tadic M, Gherbesi E, Faggiano A, Sala C, Carugo S, Cuspidi C. The impact of continuous positive airway pressure on cardiac mechanics: Findings from a meta-analysis of echocardiographic studies. Journal of clinical hypertension (Greenwich, Conn.). 2022 Jul:24(7):795-803. doi: 10.1111/jch.14488. Epub 2022 Jun 13 [PubMed PMID: 35695237]

Level 1 (high-level) evidence

[88]

Rana AM, Sankari A. Central Sleep Apnea. StatPearls. 2023 Jan:(): [PubMed PMID: 35201727]

[89]

Maggard MD, Sankari A, Cascella M. Upper Airway Resistance Syndrome. StatPearls. 2023 Jan:(): [PubMed PMID: 33232072]