Question 1
How do different available tests compare to diagnose sleep apnea in adults with symptoms suggestive of disordered sleep?

a. How do the different tests compare in different subgroups of patients, based on: race, gender, body mass index (BMI), existing non-insulin dependent diabetes mellitus (NIDDM), existing cardiovascular disease (CVD), existing hypertension (HTN), clinical symptoms, previous stroke, airway characteristics

b. What is the agreement between various combinations of clinical signs, symptoms, and history and formal testing?

Question 2
How does phased testing (screening tests or battery followed by full test) compare to full testing alone?

Question 3
What is the effect of pre-operative screening for sleep apnea on surgical outcomes?

Question 4
What is the comparative effect of different treatments for obstructive sleep apnea (OSA) in adults?

a. Does the comparative effect of treatments vary based on presenting patient characteristics, severity of OSA, or other pre-treatment factors? Are any of these characteristics or factors predictive of treatment success?

1. Characteristics: Age, sex, race, weight, bed partner, airway and other physical characteristics, specific comorbidities
2. OSA severity or characteristics: Baseline questionnaire (etc.) results, formal testing results (including hypoxemia levels), Baseline QoL; positional dependency, REM dependency
3. Other: specific symptoms

b. Does the comparative effect of treatments vary based on the definitions of OSA used by study investigators?

Question 5
What are the pre-treatment patient-level characteristics associated with failure to adequately treat OSA?

Question 6
What is the effect of interventions to improve compliance with device (CPAP, oral appliances, positional therapy) use on clinical and intermediate outcomes?

Background

Sleep apnea is a relatively common disorder that affects all ages. The American College of Chest Physicians (ACCP) (2006) estimates the prevalence of obstructive sleep apnea in the US to be between 5-10% and asserts that as many as one in four American adults could benefit from evaluation for obstructive sleep apnea.¹ The condition is characterized by periods of disturbed airflow patterns during sleep time, namely reduced airflow (hypopnea) or airflow cessation (apnea). It is postulated that both types of airflow disturbance have similar pathophysiology and bear the same clinical significance.² Obstructive sleep apnea is by far the most common type of the condition; apneas and hypopneas of central and mixed central and obstructive etiology comprise the other forms.² Obstructive sleep apnea has been associated with a variety of adverse clinical outcomes such as mortality secondary to cardiovascular disease,^3-5 decreased quality of life,⁶ cardiac disease and stroke,^3,7 hypertension,^8-10 non-insulin dependent diabetes and other metabolic abnormalities,^5,11-14 as well as increased likelihood for motor vehicle and other accidents.^15,16

Diagnosis

The severity of sleep apnea is typically quantified by the number of apneas and hypopneas per hour of sleep, a quantity that has been termed apnea-hypopnea index (AHI). The symptom of excessive daytime sleepiness is quite variable and not always present in patients with obstructive sleep apnea; thus, most patients remain undiagnosed and untreated.⁶

There is a large amount of clinical uncertainty surrounding this condition, including inconsistencies in the definition of the disease. While in-laboratory polysomnography is considered the gold standard in clinical practice to diagnose obstructive sleep apnea, it is not without constraints such as cost, interlaboratory variation in hardware and assessment methods. The standard measurement of AHI (and by extension, the diagnosis of sleep apnea) requires a comprehensive, technologist-attended sleep study with multichannel polysomnography, which is performed in specialized sleep laboratories.^2,17 Laboratory-based polysomnography records a variety of neurophysiologic and cardiorespiratory signals and is interpreted by trained technologists and sleep physicians after the sleep study has been completed.

However, it is acknowledged that it is not a definitive test to either diagnose or rule out obstructive sleep apnea. In part, this is due to a lack of robust standardized criteria as to the test parameters measured and the thresholds of the parameters used to make the diagnosis.

Since in-laboratory polysomnography is costly, resource intensive, and burdensome to the patient, other diagnostic tools have been developed, including portable tests¹⁷ and questionnaires for pre-screening patients. There are different types of portable monitors, which gather different neurophysiologic and respiratory information and may synthesize the accumulated data differently.¹⁸ Different screening questionnaires exist to pre-screen patients for further testing or treatment. The value of the different tests and of the questionnaires and other screening tools remains unclear. There is also lack of clarity as to whether the tests can be accurately used to predict the clinical severity of patients’ sleep apnea and their likelihood of clinically important sequelae.

Pre-operative testing

People with sleep apnea are at increased risk of surgical and anesthesia-related adverse outcomes.¹⁹ Finding patients undergoing surgery with undiagnosed sleep apnea could, in theory, allow optimization of peri-opeative care to minimize problems with intubation, extubation, and other respiratory events. At present, though, the need to screen all or selected surgical patients and what method of screening is effective and efficient is unclear.

Treatment

Continuous positive airway pressure (CPAP) is the standard first-line therapy for most patients diagnosed with obstructive sleep apnea. Obstructive sleep apnea occurs when the upper airway closes or becomes overly narrow as the muscles in the oropharynx ( mouth and throat) relax during sleep. This results in inadequate or stopped breathing, which reduces oxygen in the blood and causes arousal from sleep. The CPAP machine counteracts this sequence of events by delivering compressed air to the oropharynx, splinting the airway (keeping it open with increased air pressure) so that unobstructed breathing becomes possible, reducing and/or preventing apneas and hypopneas.

For many patients, using CPAP results in immediate improvement in sleep and improvement in quality of life largely related to decreased daytime somnolence. However, it has been suggested that approximately one-quarter to one-half of patients with obstructive sleep apnea will either refuse the offer of CPAP therapy, will not tolerate it, fail to use the machine properly, or for other reasons do not comply with CPAP use.²⁰ These patients are essentially untreated and receive little or no benefit from the device.

When CPAP is refused or not tolerated, a number of second-line treatments are available including, uvulopalatopharyngoplasty (UPPP), radiofrequency ablation, jaw surgery, and bariatric surgery, for eligible candidates. UPPP, radiofrequency ablation, and jaw surgery are surgical techniques to remove or shrink and scar redundant tissue that is causing the obstruction or to otherwise minimize the obstruction. The goal of bariatric surgery is to reduce body weight and fat, which may shrink the oropharyngeal tissue causing the obstruction. However, life-threatening complications have been associated with sleep apnea surgery. Fatalities have been related to upper airway collapse or obstruction secondary to pharmacological sedation and surgical edema.21
Other less invasive techniques include oral appliances, which are worn overnight and aim to mechanically splint the oropharynx open; positional therapy, devices to prevent lying supine during sleep, a position that for many patients exacerbates the obstruction; pharyngeal or laryngeal exercises to improve muscle tone; non-surgical weight loss programs; and physical exercise programs.

Another management approach is to provide interventions that will increase compliance with CPAP use. These include structured education about the value of CPAP and how to use and adjust the CPAP; structured individual follow-up to correct any problems; group support; and relieving nasal congestion or dryness caused by the CPAP machine.

Population(s)

KQ 1-2

• Adults (>16 yo) with symptoms, findings, history, comorbidities that clinically indicate that they are at increased risk of having sleep apnea
• Exclude:
  • Neuromuscular disease, Down syndrome, Prader-Willi syndrome, major congenital skeletal abnormalities, narcolepsy, narcotic addiction
  • Children (≤16 yo)
  • (Studies of) only asymptomatic / healthy / general population / control people
  • (Studies of) only patients who carry a known diagnosis of / with known sleep apnea

KQ 3

• Pre-operative patients, all surgeries

KQ 4-6

• Diagnosed with obstructive sleep apnea (OSA)
  • Formal testing performed
  • Apnea-hypopnea index ≥5
  • With or without symptoms
  • Allow individual study investigator definitions of OSA within these parameters
• Adults (>16 yo)
• Exclude:
  • Central sleep apnea
  • Children (≤16 yo)
  • Neuromuscular disease, Down syndrome, Prader-Willi syndrome, major congenital skeletal abnormalities, narcolepsy, narcotic addiction

Interventions

KQ 1-3

• Polysomnography (Facility-based, with monitoring)
• Home monitoring devices
  • For polysomnography and home monitoring devices
    • Any combination of 2 or more “channels” (measured factors)
    • Pulse transit time (alone)
    • Peripheral arterial tone (alone)
    • Pulse oximetry (alone)
    • Exclude:
      • Heart rate (alone)
      • Heart rate variability (alone)
      • Actigraphy (alone)
      • Other single channel tests
• Standardized screening and other questionnaires, scales, etc. that include clinical criteria (eg, signs, symptoms, history, comorbidities)
  • Clinical decision-making tools
  • Exclude:
    • Single or multiple patient characteristic predictors or risk factors (eg, BMI alone) that are not part of a standardized diagnostic tool
• Include information on the FDA status, indications, and warnings for use of devices covered in the systematic review (in background material / introduction of report)

KQ 4-6

• Positive airway pressure masks (Continuous positive airway pressure [CPAP], Bilevel positive airway pressure machines [BiPAP], Auto-titrating continuous positive airway pressure [APAP], and similar devices)
• Surgery
  • Jaw or mouth
  • Airway
  • Bariatric (for weight loss)
• Oral appliances / Dental devices (mandibular advancement devices, tongue retaining devices, and similar devices)
• Positional therapy (devices to alter sleep positions)
• Physical therapy (Not KQ 6)
  • Pharyngeal or laryngeal exercises, or similar approaches
  • Only formal therapy protocols, not just advice
• Lifestyle modification (Not KQ 6)
  • Non-surgical weight loss programs
    • Only formal protocols, not just single-time advice
    • Medication (for weight loss)
  • Exercise
    • Only formal protocols, not just advice
• Include information on the FDA status, indications, and warnings for use of devices covered in the systematic review (in background material / introduction of report)

Outcomes

KQ 1-3

• Correlation, concordance, or agreement among tests
• Predictive value (sensitivity, specificity) for clinical outcomes listed under treatment KQs.
• Change in clinical management
• Clinical outcomes (listed under treatment KQs), if reported in a randomized controlled trial of diagnostic tests

KQ 3:

• Intra-operative events
• Surgical recovery events
• Surgical recovery time
• Post-surgical events
• Length of intensive care or hospital stay
• Intubation failures
• Extubation failures

Harms, Adverse events

• Any adverse events

KQ 4-5

• Sleep / wakefulness clinical outcomes
  • Quality of life
    • Disease specific (eg, Functional Outcomes of Sleep Questionnaire [FOSQ], Calgary questionnaire)
    • General (eg, Short Form survey instrument-36 [SF-36], EuroQoL EQ-5D, others but with priority given to preference-based utility scores)
  • Sleepiness / somnolence measures
    • Subjective (eg, Epworth sleepiness scales); only validated measures
    • Objective (eg, Multiple Sleep Latency Test, Maintenance of Wakefulness Test); only validated measures
  • General symptom scales (eg, diagnostic screening questionnaires); only validated measures
  • Cognitive or Executive function scales; only validated measures
  • Physical function scales; only validated measures
  • Accidents ascribed to somnolence (eg, motor vehicle, home accidents)
  • Sleep quality; only formal scales or questionnaires
  • Work days lost (and equivalent)
• Comorbidities clinical outcomes
  • Mortality
  • Cardiovascular events (Congestive heart failure symptoms, stroke, arrhythmia events, coronary artery disease events, hypertension (diagnosis, resolution, or reduction in medications)
  • Non-insulin dependent diabetes (diagnosis, resolution, start or end treatment)
• Intermediate or Surrogate outcomes
  • Sleep study measures
    • Apnea hypopnea index
    • Number of arousals
    • Time in deeper sleep stages
  • Hemoglobin A1c
  • Blood pressure
• Adherence / Compliance
  • Categorical (adhering or not adhering)
  • Time (hours) using device per time period
• Harms, Adverse events
  • Any adverse events

KQ 6

• Adherence / Compliance
  • Categorical (adhering or not adhering)
  • Time (hours) using device per time period

Timing

KQ 1-3

• Cross-sectional or longitudinal of any duration

KQ 4-6
Minimum duration:

• Sleep clinical outcomes: 4 weeks
  • Accidents, work days lost: 1 year
• Comorbidities clinical outcomes: 1 year
• Intermediate outcomes
  • Sleep study measures: No minimum duration except that not within the original sleep study; must be from a subsequent evaluation
  • Hemoglobin A1c and blood pressure: 4 weeks
• Adherence: 4 weeks (KQ 6: no minimum duration)
• Adverse events: No minimum duration

Setting

KQ 1-2

• Any setting (primary or specialty care, in-facility or home; inpatient or outpatient)

KQ 3

• Any pre-operative setting (hospital or ambulatory, any surgery)

KQ 4-6

• Any setting

Definition of Terms

See background

References

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