​With almost a third of Singaporeans affected by obstructive sleep apnoea (OSA), general practitioners are bound to encounter patients with this sleep disorder in their practice. The SingHealth Duke-NUS Sleep Centre shares an overview of the condition’s essential facts, from presentation and diagnosis to the various treatment modalities available.

WHAT IS OBSTRUCTIVE SLEEP APNOEA?

Obstructive sleep apnoea (OSA) is a condition associated with repetitive episodes of upper airway obstruction during sleep. These episodes are associated with hypoxia and arousal leading to sleep disruption.

Impact

OSA affects daytime functioning, causes poor mood, affects memory, reduces concentration and increases the risk of driving accidents.1,2

Large swings in intrathoracic pressure which occur during upper airway obstruction and hypoxia activate the sympathetic system, and lead to a range of cardiovascular and metabolic conditions.3 In elderly patients, OSA is also linked to an increased risk of cognitive impairment.4

Prevalence

OSA is highly prevalent with an estimated 30.5% of people in Singapore having moderate-severe OSA, of which up to 91% are undiagnosed.5 

RISK FACTORS

Risk factors of OSA include:

  • Obesity - Obesity is a major risk factor for OSA. Obesity-induced upper airway changes lead to airway narrowing and collapsibility during sleep.6

  • Ageing - Ageing is another important risk factor. Ageing results in greater upper airway collapsibility and reduced upper airway muscle reflex response.7

  • Certain craniofacial abnormalities - Certain craniofacial abnormalities such as tonsillar hypertrophy8 and small mandible also result in an anatomically narrow upper airway and higher rates of OSA.9

  • Gender - Men are twice as likely to have OSA than women.10

However, OSA is not just an anatomical disease. Non-anatomical factors also contribute in various degrees to the development of OSA in individual patients, including:11

  • The responsiveness of the upper airway muscles (how well the upper airway muscle tone is maintained during sleep)

  • The sensitivity of the ventilatory control system (how well breathing is regulated – an oversensitive system leads to periods of overbreathing and consequent periods of apnoea)

  • A low respiratory arousal threshold (being easily awakened in response to a mild reduction in airflow)

OSA is a heterogeneous disease with variability in pathophysiology, clinical presentation and treatment response. More work is required to understand the disease better, to aid development of individualised therapy.12

CLINICAL PRESENTATION

The most common symptom of OSA is excessive daytime sleepiness. 

Other common symptoms include:

  • Snoring

  • Witnessed apnoeic episodes

  • Waking up choking or gasping

  • Frequent nocturia due to sleep arousal

While the typical profile of an OSA patient is male, middle-aged, overweight and snores loudly, it is important to be aware that OSA can present in a variety of ways.

  • Women with OSA are more likely to complain of symptoms of frequent awakening (sleep maintenance insomnia), restless legs, depression and nightmares rather than snoring and apnoeic episodes.13

  • Elderly patients have a normal advancement in circadian rhythm in which they tend to sleep earlier, wake up earlier and sleep shorter hours. Elderly patients also have higher rates of symptoms such as nocturia and reduced energy levels.

    Thus, symptoms such as insomnia, frequent daytime naps and nocturia can easily be mistaken as part of the functional impairments of ageing, or the effects of disease or medications. Elderly patients may also present with predominantly neurocognitive effects such as poor memory.4,7

Although excessive daytime sleepiness is the most common symptom, cohort studies have shown that there are subsets of patients who are asymptomatic despite sleep disruption from OSA.14


Diagnostic Sleep Studies

If a patient has symptoms suggestive of OSA, they should be referred for a sleep study.

1. IN-LABORATORY POLYSOMNOGRAPHY

How it is performed

An in-laboratory polysomnography (PSG) is the standard diagnostic test.

Patients are admitted overnight for the study. A PSG is performed with continuous measures of airflow, respiratory effort, pulse oximetry, electroencephalogram, chin electromyogram, electrooculogram, body position and leg movement during sleep. It can diagnose OSA and other respiratory or non-respiratory sleep disorders.

2. HOME SLEEP STUDY

How it is performed

Home sleep studies are increasingly being used for the diagnosis of OSA as well. These tests can be conducted in the convenience of the patient’s own home. It utilises fewer signals than a PSG, typically including measures of airflow, respiratory effort and pulse oximetry or peripheral arterial tonometry (PAT) with oximetry and actigraphy.

Accuracy and limitations

Home sleep studies have good sensitivity (79% [95% CI, 71-86%]) and specificity (79% [95% CI, 63-89%]) for moderate-severe OSA15 and can be used accurately in patients with a high pre-test probability of OSA.

However, its accuracy goes down in patients who have a low pre-test probability of OSA. 

Without the range of signals available in a PSG, home sleep studies are also not able to diagnose other sleep disorders aside from OSA (e.g., hypoventilation, periodic limb movement disorder).16

When it should be used

Therefore, home sleep studies should primarily be used to diagnose OSA in patients with a high clinical suspicion of OSA and no other suspected sleep disorders.

Practice guidelines from the American Academy of Sleep Medicine define a high clinical suspicion of OSA as patients who have excessive daytime sleepiness and two of the three criteria below:

  • Snoring
  • Witnessed apnoea or choking or gasping
  • Hypertension

As false negative home sleep studies can occur, a negative home sleep study in patients with a high clinical suspicion of OSA should be followed by an in-laboratory PSG.15


Treatment Options

The treatment decision depends on the patient’s symptom severity, severity of OSA, BMI, phenotypic traits, comorbidities and personal wishes.

1. CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) THERAPY

What it is

CPAP is the primary treatment for symptomatic OSA. It is delivered via a nasal or oronasal mask, and the pressure acts to splint the airway open during sleep.

Efficacy

CPAP is effective in reducing the apnoea-hypopnoea index (AHI), improving daytime sleepiness and improving neurocognitive outcomes.17,18 The treatment effect of CPAP is the greatest in patients who have higher levels of daytime sleepiness and thus should be offered to all patients who are symptomatic.

CPAP has also been shown in studies to reduce blood pressure. The treatment effect is modest but higher in the subset of patients with resistant hypertension (mean reduction in systolic blood pressure 5.06 mmHg, diastolic blood pressure 4.21 mmHg).19

CPAP and cardiovascular disease

Despite the association of OSA with cardiovascular disease, a recent large randomised controlled trial (RCT) (the Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome [ISAACC] trial) has failed to show that the use of CPAP in patients with acute coronary syndrome reduces future cardiovascular events.20

A major limitation of the study is that patients with excessive daytime sleepiness were excluded and there was a low adherence to CPAP therapy (2.78 hours/night).

As the degree of excessive daytime sleepiness is correlated with an increased risk of cardiovascular disease21, the exclusion of sleepy patients may underestimate the treatment effect of CPAP.

However, from this RCT as well as earlier trials22,23, the current evidence suggests that CPAP therapy does not reduce cardiovascular risk in asymptomatic or minimally symptomatic patients. 

Nevertheless, screening may still be appropriate in a subset of patients with resistant hypertension, pulmonary hypertension and recurrent atrial fibrillation after cardioversion or ablation.24

Importance of CPAP adherance

As previously alluded to, the benefits of CPAP are highly dependent on adherence; more hours used per night is associated with greater improvement in symptoms and function.25

Unfortunately, acceptance of and compliance to CPAP therapy is challenging. 

In a study performed at Changi General Hospital, only 34.8% of patients with newly diagnosed OSA opted to try CPAP and only 50.7% continued therapy after the initial trial period. However, in those who continued CPAP, 78.5% were adherent after one year.26

Predictors of compliance to CPAP include severity of OSA, severity of excessive daytime sleepiness, psychosocial factors and side effects.27

CPAP adherence can be improved through patient (and bed partner) education, patient engagement, troubleshooting side effects and cognitive behavioural therapy.27 Thus, these are essential components of CPAP therapy and follow-up service.

2. SURGERY

Who can benefit from surgery

Surgery is suitable for selected patients. It can be used as:

  • An adjunct to facilitate CPAP therapy in patients with inadequate CPAP adherence due to pressure-related side effects

    Surgery to facilitate CPAP therapy involves nasal, tonsillar or palatal surgery to increase the patency of the upper airway in patients who have significant CPAP pressure-related side effects. By widening the airway, CPAP pressure requirements are reduced, resulting in improved patient adherence to therapy.30

  • Sole treatment for OSA in patients who are intolerant of CPAP or have surgically amenable upper airway abnormalities (such as tonsillar hypertrophy or maxillomandibular abnormalities)28

    For patients with surgically amenable upper airway abnormalities, surgery can be effective. For example, in patients with tonsillar hypertrophy, tonsillectomy normalises AHI for 57.4% of patients, reduces AHI by more than half in 85.2% of patients and improves daytime sleepiness.31

In most cases, even in patients with significant craniofacial abnormalities, a trial of CPAP therapy prior to surgery is usually performed as it carries minimal risk relative to surgery.28

Pre-surgery assessment

Surgery for OSA is individualised. Various manoeuvres are performed during nasoendoscopy to assess the collapsibility of the airway, identify the area of obstruction and test the effect of surgery. 

If the site of obstruction is not identified during awake endoscopy, evaluation may be performed with drug-induced sleep endoscopy (DISE), which has been shown to alter surgical decisions in a significant proportion of patients.29

Hypoglossal nerve stimulation

Hypoglossal nerve stimulation is a relatively newer form of surgical treatment for moderate-severe OSA. An electrode is placed near the hypoglossal nerve and controlled by a stimulator implanted on the chest. In response to respiratory effort detected via a pressure sensor, the stimulator activates the hypoglossal nerve causing tongue protrusion and maintaining upper airway patency.

Upper airway stimulation reduces the median AHI from 29.3 to 9 events per hour and improves daytime sleepiness.32 Sustained benefit is seen at five years follow-up.33

3. ORAL APPLIANCE

What it is

Mandibular advancement devices (MAD) are the most common oral appliances used for OSA and should be custom-fitted by a dentist trained in dental sleep medicine.34 They consist of braces that cover the upper and lower teeth. 

The lower teeth (and mandible) are then advanced forward resulting in increased upper airway volume. The degree of advancement is titrated to patient tolerance and a follow-up sleep study is usually performed to confirm treatment efficacy.

Efficacy

MADs are an effective form of treatment for patients with mild-moderate OSA and are well tolerated by patients.

While MADs reduce AHI less than CPAP therapy (mean reduction in AHI of 13.6 events per hour), they are associated with greater compliance and thus improve daytime sleepiness to a similar degree.34 MADs are therefore a useful alternative in patients who are intolerant of CPAP.

4. POSITIONAL THERAPY AND MYOFUNCTIONAL THERAPY

Positional therapy

In patients whose OSA is predominantly in a supine position and less in the lateral position (positional OSA), sleeping on one’s side is an effective treatment with good compliance.35

Various devices such as specifically designed pillows or supine vibration alarm devices are available to help restrict sleep to the side.36

Myofunctional therapy

Myofunctional therapy consists of combinations of oropharyngeal exercises involving the palate, tongue and facial muscles. It improves snoring and daytime sleepiness.37

It is inferior to CPAP therapy but may have a role to play in patients who are CPAP-intolerant.37 Used as an adjunct in combination with CPAP, myofunctional therapy also results in improved CPAP compliance.38

5. LIFESTYLE MODIFICATION

Lifestyle modification such as exercise and weight management are important interventions not to be forgotten.

Weight loss

In OSA patients who are overweight or obese, weight loss decreases OSA severity and improves daytime sleepiness, snoring and general health. 

There is no threshold amount of weight loss needed; greater weight loss is associated with greater benefit.39

Exercise

Exercise by itself can also improve OSA. In a small trial, subjects who performed 30 minutes of moderate-intensity walking a day, five days a week, have a mean reduction in AHI of 10.6 events per hour.40

Importantly, this benefit occurs independently from a change in weight and thus can be prescribed even to non-obese individuals with OSA. 

Minimising alcohol and medications

Alcohol and medications such as benzodiazepines and opioids may worsen OSA and should be minimised or avoided.


GP REFERRALS TO THE SINGHEALTH DUKE-NUS SLEEP CENTRE

If OSA is suspected, GPs may refer patients to a specialist centre such as the SingHealth Duke-NUS Sleep Centre for an assessment. 

The SingHealth Duke-NUS Sleep Centre, which sees patients at six clinical sites across SingHealth institutions, is the largest multidisciplinary sleep service in Singapore and is staffed by specialists from ENT surgery, respiratory medicine, neurology, psychiatry, psychology and dentistry – all of whom have undergone further specialised training in the field of sleep medicine locally and abroad.


​TAKE-HOME MESSAGES

  • OSA is a common condition and many patients are undiagnosed. 

  • Women and elderly patients with OSA may present without typical symptoms. 

  • Home sleep studies can be used to accurately diagnose, but not rule out, OSA in patients with a high clinical suspicion of OSA and no other suspected sleep disorder.

  • Symptomatic patients appear to benefit the most from OSA treatment.

  • Lifestyle modification such as exercise and weight management should not be forgotten as a form of treatment for OSA.

  • CPAP is the primary therapy for OSA, but adherence is often suboptimal. Alternative treatments such as surgery, oral appliances, positional therapy and myofunctional therapy are available.


REFERENCES

  1. Seda G, Han TS. Effect of Obstructive Sleep Apnea on Neurocognitive Performance. Sleep Med Clin. 2020 Mar;15(1):77-85.

  2. Tregear S, Reston J, Schoelles K, et al. Obstructive sleep apnea and risk of motor vehicle crash: systematic review and meta-analysis. J Clin Sleep Med. 2009 Dec 15;5(6):573-81.

  3. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93.

  4. Leng Y, McEvoy CT, Allen IE, et al. Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive Impairment: A Systematic Review and Meta-analysis . JAMA Neurol. 2017;74(10):1237–1245.

  5. Tan A, Cheung YY, Yin J, et al. Prevalence of sleep-disordered breathing in a multiethnic Asian population in Singapore: A community-based study. Respirology. 2016 Jul;21(5):943-50.

  6. Schwartz AR, Patil SP, Laffan AM, et al. Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches. Proc Am Thorac Soc. 2008 Feb 15;5(2):185-92.

  7. Glasser M, Bailey N, McMillan A, et al. Sleep apnoea in older people. Breathe. Mar 2011, 7 (3) 248-256.

  8. Wang, J, Zhao, Y, Yang W, et al. Correlations between obstructive sleep apnea and adenotonsillar hypertrophy in children of different weight status. Sci Rep 9, 11455 (2019).

  9. Chi L, Comyn FL, Mitra N, et al. Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MR. Eur Respir J. Aug 2011, 38 (2) 348-358.

  10. Huang T, Lin BM, Markt SC, et al. Sex differences in the associations of obstructive sleep apnoea with epidemiological factors. Eur Respir J. 2018 Mar 15;51(3):1702421.

  11. Eckert DJ, White DP, Jordan AS, et al. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013 Oct 15;188(8):996-1004.

  12. McNicholas WT, Pevernagie D. Obstructive sleep apnea: transition from pathophysiology to an integrative disease model. J Sleep Res. 2022 Aug;31(4):e13616. doi: 10.1111/jsr.13616.

  13. Valipour A, Lothaller H, Rauscher H, et al. Gender-related differences in symptoms of patients with suspected breathing disorders in sleep: a clinical population study using the sleep disorders questionnaire. Sleep. 2007 Mar;30(3):312-9.

  14. Ye L, Pien G.W, Ratcliffe S.J, et al. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J. Dec 2014, 44 (6) 1600-1607.

  15. El Shayeb M, Topfer LA, Stafinski T, et al. Diagnostic accuracy of level 3 portable sleep tests versus level 1 polysomnography for sleep-disordered breathing: a systematic review and meta-analysis. CMAJ. 2014 Jan 7;186(1):E25-51.

  16. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(3):479–504.

  17. Patil SP, Ayappa IA, Caples SM, et al. Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2019;15(2):301–334.

  18. Pollicina I, Maniaci A, Lechien JR, et al. Neurocognitive Performance Improvement after Obstructive Sleep Apnea Treatment: State of the Art. Behav Sci (Basel). 2021 Dec 16;11(12):180.

  19. Labarca G, Schmidt A, Dreyse J, et al. Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): Systematic review and meta-analysis. Sleep Med Rev. 2021 Aug;58:101446.

  20. Sánchez-de-la-Torre M, Sánchez-de-la-Torre A, Bertran S, et al. 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. Lancet Respir Med. 2020 Apr;8(4):359-367.

  21. Mazzotti DR, Keenan BT, Lim DC, et al. Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes. Am J Respir Crit Care Med. 2019 Aug 15;200(4):493-506.

  22. McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016;375:919- 31.

  23. Peker Y, Glantz H, Eulenburg C, et al. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial. Am J Respir Crit Care Med 2016;194:613-20.

  24. Yeghiazarians Y, Jneid H, Tietjens JR, et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021 Jul 20;144(3):e56-e67.

  25. Weaver TE, Maislin G, Dinges DF, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007 Jun;30(6):711-9.

  26. Tan B, Tan A, Chan YH, et al. Adherence to Continuous Positive Airway Pressure therapy in Singaporean patients with Obstructive Sleep Apnea. Am J Otolaryngol. 2018 Sep-Oct;39(5):501-506.

  27. Mehrtash M, Bakker J.P, Ayas N. Predictors of Continuous Positive Airway Pressure Adherence in Patients with Obstructive Sleep Apnea. Lung 197, 115–121 (2019).

  28. Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(12):2499–2505.

  29. Albdah A A, Alkusayer M M, Al-Kadi M, et al. (October 30, 2019) The Impact of Drug-induced Sleep Endoscopy on Therapeutic Decisions in Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Cureus 11(10): e6041.

  30. Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507–2531.

  31. Camacho M, Li D, Kawai M, Zaghi S, Teixeira J, Senchak AJ, Brietzke SE, Frasier S, Certal V. Tonsillectomy for adult obstructive sleep apnea: A systematic review and meta-analysis. Laryngoscope. 2016 Sep;126(9):2176-86. doi: 10.1002/lary.25931. Epub 2016 Mar 22. PMID: 27005314.

  32. Strollo PJ Jr, Soose RJ, Maurer JT, et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014 Jan 9;370(2):139-49.

  33. Woodson BT, Strohl KP, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes. Otolaryngol Head Neck Surg. 2018 Jul;159(1):194-202.

  34. 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 2015;11(7):773–827.

  35. Srijithesh PR, Aghoram R, Goel A, et al. Positional therapy for obstructive sleep apnoea. Cochrane Database Syst Rev. 2019 May 1;5(5):CD010990.

  36. Ravesloot MJ, White D, Heinzer R, Oksenberg A, Pépin JL. Efficacy of the new generation of devices for positional therapy for patients with positional obstructive sleep apnea: a systematic review of the literature and meta-analysis. J Clin Sleep Med. 2017;13(6):813–824.

  37. Rueda J-R, Mugueta-Aguinaga I, Vilaró J, et al. Myofunctional therapy (oropharyngeal exercises) for obstructive sleep apnoea. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD013449.

  38. Diaféria G, Santos-Silva R, Truksinas E, et al. Myofunctional therapy improves adherence to continuous positive airway pressure treatment. Sleep Breath. 2017 May;21(2):387-395.

  39. Hudgel DW, Patel SR, Ahasic AM, et al. American Thoracic Society Assembly on Sleep and Respiratory Neurobiology. The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 15;198(6):e70-e87.

  40. Mendelson M, Lyons OD, Yadollahi A, et al. Effects of exercise training on sleep apnoea in patients with coronary artery disease: a randomised trial. Eur Respir J. 2016 Jul;48(1):142-50.


Dr Marcus Sim is an Associate Consultant Respiratory Physician at Changi General Hospital. His areas of clinical interest are obstructive sleep apnoea, obesity hypoventilation syndrome and chronic non-invasive ventilation use in chronic respiratory failure patients.


GPs can call the SingHealth Duke-NUS Sleep Centre for appointments at the following hotlines or click here to visit the website:

Singapore General Hospital: 6326 6060
Changi General Hospital: 6788 3003
Sengkang General Hospital: 6930 6000
KK Women's and Children's Hospital: 6692 2984
National Dental Centre Singapore: 6324 8798
National Neuroscience Institute: 6330 6363