American Journal of Respiratory and Critical Care Medicine

Is obstructive sleep apnea an anatomic disorder? Of course it is; there is no real debate. Just examine the patient population. Patients with sleep apnea almost invariably are either obese or have abnormal upper airway anatomy (retrognathia, tonsillar hypertrophy, macroglossia, enlargement of the lateral peritonsillar folds, enlargement/elongation of the soft palate). Obesity increases the size of the upper airway soft tissue structures (including the parapharygneal fat pads) (14), which decreases the size of the upper airway, which in turn predisposes to sleep apnea. How many patients with sleep apnea are not obese or do not have abnormal upper airway anatomy? Very, very few. Patients with normal upper airway anatomy do not have sleep apnea (5). The primary risk factors for sleep apnea include obesity, increased neck size, changes in craniofacial structures (particularly retrognathia), and enlargement of the upper airway soft tissue structures; all these risk factors alter upper airway anatomy. Obviously obstructive sleep apnea is a state-dependent condition occurring only during sleep and not during wakefulness. But it is the anatomic compromise that allows the reduction in motor activity of airway dilator muscles that occurs in all of us during sleep to have such profound effects. There are no data that enhanced reduction of upper airway muscle tone (which occurs during sleep) on its own is a risk factor for sleep apnea. Nonetheless, upper airway muscle tone is a component of the pathogenesis of sleep apnea, but it is only important in patients who have underlying abnormal upper airway anatomy. Individuals with normal upper airway anatomy do not develop obstructive apneas or hypopneas during sleep even though they have a reduction in muscle tone and a reduction in the caliber of their upper airway (6, 7). In addition, all the therapeutic options for obstructive sleep apnea (continuous positive airway pressure , weight loss, oral appliances, and upper airway surgery) increase upper airway caliber by altering upper airway anatomy. Because the risk factors are structural and the treatment options for sleep-disordered breathing are all based on enlarging the upper airway, it is clear that sleep apnea must be an anatomic disorder. Now let me review, in more detail, the evidence for this statement.

What are the most important risk factors for obstructive sleep apnea? The best studied are obesity and increased neck size, both of which directly affect upper airway caliber. In the Wisconsin Sleep Cohort Study (8) an increase in body mass index by 1 SD tripled the prevalence of sleep apnea. Neck size was the strongest predictor of sleep-disordered breathing among all anthropomorphic variables studied (8). Increased neck size has been demonstrated in other population studies to be an important predictor of sleep apnea (9, 10). That neck circumference is a strong predictor of sleep-disordered breathing indicates that upper body obesity (fat deposition around the upper airway or fat deposited in the parapharyngeal fat pads), rather than a more generalized distribution of body fat, is important for the development of sleep apnea. In fact, studies have shown that parapharyngeal fat pad volume is greater in obese subjects developing apnea than in nonobese subjects developing apnea (14). Moreover, nonobese subjects developing apnea have larger parapharyngeal fat pads than normal subjects (1). However, it is not just the parapharyngeal fat pads that are enlarged in patients with obstructive sleep apnea.

Recent studies using three-dimensional magnetic resonance imaging analysis techniques have confirmed that the volume of the upper airway soft tissue structures are enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea (3). In this investigation, a case–control design was used to examine upper airway soft tissue structures in 48 control subjects and 48 patients with sleep apnea. After covariate adjustments (gender, ethnicity, age, craniofacial size, and visceral neck fat) the volume of the lateral pharyngeal walls, tongue, and total soft tissue were significantly larger in patients with sleep apnea than in normal subjects. Not only were these structures enlarged in patients with sleep apnea compared with normal subjects, there was a significantly increased risk of developing sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue. These data provide very strong support for the importance of upper airway anatomy in predisposing patients to sleep-disordered breathing.

In addition to changes in upper airway soft tissue structures, alterations in craniofacial structures have also been shown to predispose patients to obstructive sleep apnea. Numerous studies using cephalometrics have demonstrated craniofacial abnormalities in patients with obstructive sleep apnea compared with age- and gender-matched control subjects (1113). These studies, in general, have demonstrated that patients with sleep apnea have a small, retroposed mandible, narrow posterior airway space, enlarged tongue, and soft palate, inferiorly positioned hyoid bone, and retroposition of the maxilla. These craniofacial risk factors have been reported to have their strongest association with sleep apnea in nonobese patients (14). Several studies have also demonstrated family aggregation of craniofacial morphology (reduction in posterior airway space, increase in mandibular to hyoid distance, inferior hyoid placement) in patients with sleep apnea (15, 16). The data from these studies indicate that elements of craniofacial structure in patients with sleep apnea are inherited. Demonstrating heritability of upper airway structures provides further support for the importance of upper airway anatomy in the pathogenesis of obstructive sleep apnea.

Evidence for the importance of upper airway anatomy in obstructive sleep apnea is also found by examining the treatment options for this condition. Why do continuous positive airway pressure, weight loss, oral appliances, and upper airway surgery correct sleep apnea? Because each of these therapeutic options increases upper airway caliber. CPAP increases upper airway caliber threefold (17). Weight loss increases upper airway caliber by decreasing the size of the parapharyngeal fat pads and lateral pharyngeal walls (4). Oral appliances are believed to pull the jaw forward (18), and upper airway surgery clearly alters pharyngeal anatomy. The effectiveness of uvulopalatopharyngoplasty is debatable, but that is likely because it does not alter enough upper airway soft tissue anatomy (19). Maxillomandibular surgery that affects a greater proportion of the upper airway has been shown to have a high success rate in patients with sleep apnea (20).

Even Charles Dickens in 1836 in The Pickwick Papers recognized that sleep apnea was an anatomic disorder in his detailed description of the “fat boy Joe”:

and on the box sat a fat and red faced boy, in a state of somnolency … “Joe!—damn that boy, he's gone to sleep again.” … The fat boy rolled slowly off the box … “Joe, Joe!” said the stout gentleman. “Damn that boy, he's gone to sleep again. Be good enough to pinch him, sir–in the leg, nothing else wakes him … Joe! Joe!” … [He] taps on the head with a stick, and the fat boy, with some difficulty, roused from his lethargy. “Come hand in the eatables.” There was something in the sound of the last word which roused the unctuous boy. He jumped up and the leaden eyes, which twinkled behind his mountainous cheeks, leered horribly upon the food…

Even Dickens was able to connect obesity and symptoms of sleep apnea well before the modern medical era.

Is obstructive sleep apnea an anatomic disorder? Of course it is; enough said.

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