I. Definition:

  1. Periodic apneic or hypopneic episodes during sleep associated with
  2. Upper airway obstruction due to pharyngeal collapse, leading to
  3. Awakening and resulting restoration of airway patency
  4. Sleep recurs almost immediately and the cycle repeats itself, often hundreds of times each night

II. Epidemiology

  1. Prevalence estimated at 4% male; 2% female (NEJM 328:1230, 1993)
  1. May be as much as 40-50% of hypertensives and
  2. 90% of pts with nocturnal angina (Lancet 4/29/95)
  1. Incidence greatest age 40-60
  2. Highly underdiagnosed, perhaps b/c of the gradual onset of sx
  1. More underdiagnosed in women than men. Mean duration of sx before dx in one series of women was 10y

III. Pathogenesis

  1. There is normally a moderate degree of hypoventilation during sleep resulting from partial pharyngeal collapse and resulting increase in upper airway resistance. This is due to decreased activity of the "upper airway dilator musculature" during sleep. Even occasional apneic or hypopneic episodes are normal, esp. in elderly. However, prolonged and repetitive apneic/hypopneic episodes are not normal.
  2. Structural factors
  1. In most OSA patients, there are no evident structural abnormalities. Most experts, however, believe that subtle underlying structural factors are involved:
  1. Narrower upper airway (OSA patients have narrower upper airways on average, but there' much overlap)
  2. More "collapsible" airways (+/- evidence for this)
  1. In rare instances, clear structural abnormalities are found, inc. nasal obstructing lesions, deviated nasal septum, chronic rhinitis, micrognathia, masses of the soft palate, large T & A's
  2. Structural abnormalities may play a larger role in women
  1. 48% of women with OSA in one series had abnormalities of the hard palate; >70% with mild OSA
  2. In one series of women with OSA, most weren't overweight, but BMI was correlated with severity (freq. of apneic/hypopneic episodes)
  1. Functional factors
  1. OSA pts may have altered sleep influences on palatal muscle control, e.g. the reflexes which normally keep palate open during inspiration
  2. May have impaired ventilatory drive or arousal mechanisms
  1. Obesity
  1. A major risk factor; 2/3 OSA pts in early series were overweight. Reason for association is unknown, but distribution of fat may be important: OSA pts, c/w weight-matched controls, have more fat deposition in tongue, palate, and pharynx
  2. Menopausal status not an independent factor for presence or severity of OSA when BMI is controlled for
  1. Secondary causes of OSA
  1. Hypothyroidism (unclear why, several unfounded theories exist)
  2. Neuromyopathies of any cause
  3. Acromegaly
  4. Certain congenital disorders (Prader-Willi, Down's)-unknown mechanism
  5. Respiratory depressants, e.g. EtOH, sedative-hypnotics, and maybe benzos

IV. Clinical variants

  1. Obesity hypoventilation sd. ("Pickwickian Sd.")
  1. 5% of pts with OSA
  2. Chronic wakeful hypoventilation with hypercapnia and hypoxia, due to reduced tidal volume
  3. Us. have prolonged apneas with severe desats while asleep
  4. Us. have sustained pulm. HTN and cor pulmonale
  5. Unclear pathogenesis; us. resolves with standard OSA tx.
  1. Central sleep apnea; a totally distinct entity in which reduced ventilatory effort initiates the apneic/hypopneic episode
  1. Can be due to brainstem dysfunction or to CHF
  2. Same sequelae as OSA
  3. Tx = CPAP (unclear why it works); Diamox; occasionally, noct. mechanical ventilation is used
  1. "Upper airway resistance sd"-sort of a mini-OSA
  1. Too few apneas/hypopneas during sleep to qualify as OSA, but do have frequent arousals
  2. Unclear clinical significance, but ass'd with daytime sleepiness
  3. Improves with CPAP just like OSA
  1. Plain old garden-variety snoring
  1. Prevalence 20% adults, 60% males over 40yo
  2. Risk factors are the same as for OSA
  3. May be a "pre-OSA state"-may be ass'd (though unclear if independently so) with HTN, CAD, ischemic stroke

V. Clinical sequelae of OSA are serious and account for inc. mortality in these pts.; mostly related to disrupted sleep & periodic hypoxemia

  1. Disrupted sleep
  1. Daytime sleepiness which accumulates with time; may interfere with activities requiring concentration, e.g. driving
  2. If severe or long in duration, further complications include personality changes, cognitive impairment, decreased libido, impotence, etc.
  3. 41% of women with OSA attributed breakups with a sig. other to chronic fatigue, compared with 6% of men
  1. Periodic hypoxemia
  1. Cardiovascular effects are the most troublesome; note that, at least initially in the disease process, a) and b) only occur during periods of apnea, but their hemodynamic consequences are nonetheless profound.
  1. Pulmonary hypertension results from reflex pulmonary arterial constriction
  1. Cor pulmonale can result
  1. Systemic hypertension occurs in 50% of pts from inc. sympathetic outflow during periods of awakening
  1. LV dysfunction can result
  2. In pts with CHF and LV dysfn, degree of LV dysfn correlates independently with presence of sleep apnea (n = 42) (Ann. Int. Med. 122:487, 1995)
  3. Cardiac arrhythmias, MI and sudden death follow
  4. CVA's are more common in OSA pts, poss. due to:
  1. Polycythemia
  1. Menstrual irregularities (amenorrhea, long or irreg. cycles)
  1. Occur in 43% of women with OSA; reasons unclear
  2. Decrease with treatment with CPAP
  3. Not correlated with severity of OSA or with BMI
  1. Morning headache occurs in 48%; CPAP helps; unclear cause
  2. Ass'd with increased risk for Hypertension (BMJ 320:479, 2000--JW)
  3. NOTE that some of the alleged pathophysiological sequelae of OSA have been challenged; one review of the literature on the relation between OSA and various outcomes stated that most studies were porrly designed and weak or contradictory evidence was found for link between OSA and arrhythmia, CAD, CHF, and HTN; also claimed little evidence for mortality reduction with CPAP (BMJ 314:851, 1997-JW)

VI. Diagnosis

  1. Hx
  1. Daytime sleepiness
  2. If suspicious, ask sleep partner re: snoring, apnea, awakening with a snort
  3. Morning headaches
  4. Hypothyroidism symptoms
  5. Menstrual irregularities
  6. The "Berlin Questionnaire," intended for screening for OSA, predicts likelihood of sig. OSA better than any single symptom (Ann. Int. Med. 131:535, 1999--AFP)
    1. Has your weight increased?
    2. Do you snore? (if so, queries re: loudness, frequency, whether bothers others)
    3. How often have your breathing pauses been noticed?
    4. Are you tired after sleeping?
    5. Are you tired during waketime?
    6. Have you ever fallen asleep while driving?
    7. Do you have high blood pressure?
  1. Px
  1. Upper airway exam looking for items listed above
  2. External neck circumference (Am. Rev. Resp. Dis. 141:1228, 1990: 123 pts referred for suspected OSA; external neck circumference (enc) measured at sup. border of cricothyroid with pt in upright position; avg. enc. in OSA pts = 43.7 cm vs. 39.6 cm, p < 0.0001; incidentally, enc correlated with BMI but not height)
  3. Hypothyroidism signs
  4. Remember, obesity is not a prerequisite for OSA!
  1. Labs
  1. Thyroid screen
  2. HCT
  3. ABG if suspect Pickwickian Sd.
  1. Polysomnography = gold standard but expensive; more limited (cheaper) somnography may be ok if suspicion of OSA is high

VII. Treatment-exactly who benefits from tx and how much are unanswered question. Individual results vary, and subjective improvement may not correlate with reduction in apneic episodes, so must do followup polysomnography to assess response to tx.

  1. Control risk factors
  1. Weight loss decreases sx and frequency of apneic episodes
  2. Stop EtOH and sedative drugs
  3. Changing sleep position from supine to L. lat. decub. may reduce frequency of desturations
  4. Treat hypothyroidism, acromegaly, chronic rhinitis if present
  1. Nasal continuous positive airway pressure ("CPAP")
  1. Improves sx in men and women (inc. HA's, menstrual irregularities), improves HTN, LV fn; may reduce mortality
  2. Sx return to baseline when CPAP d/c'd
  3. Long-term compiance < 66% because of discomfort, etc.
    1. Short-term use of hypnotics to improve compliance
      1. Eszopiclone (Lunesta) x 14d vs. placebo was associated with sig. increased compliance with CPAP at 6mos in one randomized trial (Ann. Int. Med. 151:696, 2009-JW)
  4. Must do polysomnography initially to determine level of pressure needed
  5. Effect of CPAP on clinical outcomes in patients with OSA
    1. In a study in 723 pts withOSA (but not daytime sleepiness) and no prior h/o cardiovascular events randomized to CPAP or no active intervention, over median 4y f/u, there was no sig. diff in incidence of (systemic hypertension or cardiovascular event) (JAMA 307:2161, 2012-abst)
  1. "Oral appliances"
  1. Many different ones on the market, few with proven benefit
  1. An oral appliance that attaches to upper teeth, pushes the mandible forward, and enlarges the upper airway in comparison to nasal CPAP was tried in 25 pts with OSA. Not as frequently successful as n-CPAP at reducing sx and apneas (12/19 as opposed to 13/13 for n-CPAP in pts who would try it; pts much more satisfied with the oral appliance, though) (Chest 109:1269, 1996)
  1. Certain dental orthoses may resuce sx and be tol'd well
  2. "Mandibular advancement device" promising in one uncontrolled trial (Chest 113:707, 1998--JW)
  3. What sounds like the same device resulted in sig. reduction in apnea/hypopnea indices in comparison with a sham control appliance ; "complete responses" were seen in 38% of pts randomized to use the device (Am. J. Resp. Crit. Care Med. 163:1457, 2001--JW)
  4. In a randomized trial in 95 pts with mild-mod OSA, a mandibular advancement device was ass'd with sig. higher "success rate" (reduction of at least 50% in apnea index) c/w UPPP (see above) at 4y f/u (63% vs. 33%) (Chest 121:739, 2002--AFP)
  1. Upper airway surgery
  1. For specific structural abnormalities (see above III.B.2); may not obviate need for other tx
  2. Uvulopalatopharyngoplasty (UPPP); not as popular as when introduced in 1981; results in temporary reduction in sx without sig. reduction in apneic episodes; probably doesn't affect mortality
  3. Tracheostomy as a last resort; does decrease mortality
  4. In children
    1. In a nonrandomized prospective study of children 1-18yo (220 with OSA, 130 of whom underwent adenotonsillectomy), the incidence of URIs for 1y post-op was sig. lower in the surgery group than the non-surgery group (Peds 113:351, 2004-AFP)
    2. In a retrospective study in 578 generally healthy children with OSA (8mos-18yo) who underwent adenotonsillectomy, 90% of children had reduction in the apnea-hypopnea index post-op but 22% still met criteria for OSA.  (Am. J. Resp. Crit. Care Med. 182:676, 2010-JW)
  1. Drugs
  1. Protryptiline; may help in mild OSA but side f/x are significant; 2nd-line to CPAP
  2. Ventilatory stimulants, e.g. Provera; only useful if Pickwickian, i.e. with wakeful hypoventilation; usually not needed if OSA adequately treated with above modalities
  3. Wakefulness-promoting drugs
    1. Modafinil (Provigil)--In a randomized trial of 157 pts with OSA and daytime somnolence despite CPAP use, modafinil 200mg/d increasing to 400mg/d after 1wk was, at 4wk f/u, ass'd with sig. less sleepiness than placebo; side f/x noted to be greater than with placebo were HA and nervousness (Am. J. Resp. Crit. Care Med. 164:1675, 2001--JW)
  1. Supplemental O2
  1. May help in mild cases; may also prolong apneic periods
  1. Nasal BiPap
  1. Expensive! But may be better tolerated than CPAP because mean resp. pressure support is less
  1. On the horizon...
  1. "Intelligent CPAP": since need for CPAP fluctuates with each breath, and the lower the pressure given the better pt. tolerance, these new machines self-adjust the CPAP pressure based on measured O2 sat, snoring, apnea, etc.
  2. Electrical stim. of tongue mm. may reduce freq. of apneic episodes and desats; still experimental

(Sources: Disease-a-month, 4/94; Lancet 344:653, 1994; 344: 656, 1994; Ann. Int. Med. 122: 493, 1995)