An obstructive sleep apnea (OSA) episode occurs when the soft tissues of the upper airway and tongue relax during sleep and block the flow of air into the lungs. These disruptions to breathing lead to intermittent blood gas disturbances (hypercapnia and hypoxemia) and are associated with increasing respiratory efforts and a brief awakening from sleep (arousal). Finally, pharyngeal activity is restored, the airway opens and hyperventilation occur in an attempt to recover oxygen and carbon dioxide levels and the patient fall back to sleep (figure 4). This does not happen during wakefulness as there is a protective mechanism which maintain the airway patency (Jyothi et al., 2019).
In severe cases disruptions to breathing can occur more than 100 times per hour, with each typically lasting 20–40 seconds, and these episodes reduce both deep NREM (non-rapid eye movement) and REM (rapid eye movement) sleep (Eckert & Malhotra, 2008).
Sleep apnea is a multifactorial disorder but typically involves some degree of upper airway anatomical impairment. In addition, upper airway muscle function, respiratory arousal threshold and ventilatory stability are also factors in the development of OSA (figures 4–8).
The pharynx is unique in that it lacks rigid or bony support and when collapse does occur it usually happens behind the soft palate or the oropharynx (from the tip of the soft pate to the epiglottis), or both. X-ray and CT imaging also show that patients with OSA may also have a reduced mandibular length, an inferiorly positioned hyoid bone, and may have mandibular repositioning all of which can compromise the upper airway (Fogel et al., 2004). There is a definite association between changes in lung volume and the size of the upper airway (Fogel et al., 2004) and it is thought that this effect is due to tracheal tug. As the lungs expand, the trachea is pulled downward which stiffens the upper airway making it less collapsible. The importance of this effect has not been fully established but it is suspected that sleep-induced reductions in lung volume can cause increased upper airway collapsibility in non-rapid eye movement (NREM) sleep in patients with OSA (Fogel et al., 2004).
Muscle tone decreases during sleep and is at its lowest during rapid eye movement (REM) sleep. As there are over 20 muscles in the upper airway, pharyngeal collapse is possible at one or multiple sites (figure 6).
The upper airways have complex neuronal patterns that differ between muscles and play a role in the maintenance of airway patency (figure 7).
These groups of neurones within the brainstem are known to have different firing patterns according to the respiratory cycle (Fogel et al., 2004; Osman et al., 2018). For example, the genioglossus (the largest pharyngeal dilator muscle located at the base of the tongue), has six different patterns of input from the brain and ~30% of patients with OSA have poor genioglossus muscle responsiveness to airway narrowing during sleep. The control of the different upper airway muscles is therefore believed to contribute to OSA pathogenesis and can drive airway narrowing during sleep (Osman et al., 2018).
Studies have also shown that instability in respiratory control can lead to periodic breathing that can contribute to the development of OSA. Loop gain is a measurement of the tendency of the ventilatory control system to amplify respiration in response to ventilatory disturbance (figure 8). People with high loop gain have exaggerated ventilatory responses to minimal changes in CO2. This is a marker of an unstable control system (Osman et al., 2018). It is thought that ventilatory instability (or a high loop gain) can cause a cycle of hyperpnea followed by a subsequent loss of pharyngeal muscle activation and airway collapse (Fogel et al., 2004).
In most people, arousal from sleep will occur when the respiratory system is adequately driven (White, 2017). Seventy-five per cent of patients with OSA, however, have respiratory events that either terminate without an arousal or with arousal following airway reopening later during the night (Osman et al., 2018). There is wide variability in respiratory arousal threshold in both normal controls and patients with OSA and the extent to which arousal threshold can influence OSA pathophysiology depends on airway anatomy and responsiveness of upper airway muscles (figure 9).
For example, in a patient with poor anatomy and good upper airway responsiveness, a high respiratory arousal threshold is preferable to achieve stable sleep and breathing. In a patient with a poor upper airway response, a high respiratory arousal threshold will lead to longer apneas and hypopneas (White, 2017). It is also possible that a sleep disordered breathing event may propagate the next through arousal-induced hyperventilation, but this has not been well-established (White, 2017).
Visit the Sleep and Breathing conference 2019 section to learn more about phenotyping patients with OSA. Professor David White describes the importance of phenotyping in terms of the four traits of OSA to guide treatment choice.