Pathophysiology of adult obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive narrowing or collapse of the pharyngeal airway during sleep. The disorder is associated with major comorbidities including excessive daytime sleepiness and increased risk of cardiovascular disease. The underlying pathophysiology is multifactorial and may vary considerably between individuals. Important risk factors include obesity, male sex, and aging. However, the physiological mechanisms underlying these risk factors are not clearly understood. This brief review summarizes the current understanding of OSA pathophysiology in adults and highlights the potential mechanisms underlying the principal risk factors. In addition, some of the pathophysiological characteristics associated with OSA that may modulate disease severity are illustrated. Finally, the potential for novel treatment strategies, based on an improved understanding of the underlying pathophysiology, is also discussed with the ultimate aim of stimulating research ideas in areas where knowledge is lacking.

Figure 1.

Polysomnographic tracings of obstructive sleep apnea from a detailed experimental study of a patient with severe disease (apnea–hypopnea index = 56 events/h). EMGgg = Electromyogram of the genioglossus muscle (intramuscular); EMGsub = EMG of the submental muscle (surface); EEG = electroencephalogram (C3–A2); Pepi = pressure at the level of the epiglottis; Flow = airflow measured via nasal mask and pneumotachograph; Sa_O2 = arterial blood oxygen saturation measured via pulse oximetry at the finger. (A) An 8-minute segment during stage 2 sleep, during which the patient is experiencing sleep-disordered breathing. Note the repeated oxygen desaturations as a result of severely impaired (hypopnea) or absent (apnea) airflow despite continual breathing efforts (Pepi) and the cyclical breathing pattern that ensues as the patient oscillates between sleep and arousal (downward pointing arrows). (B) An expanded segment during an obstructive event. Note: Evidence of snoring on the flow tracing, quantification of the arousal threshold, and progressive increases in EMGgg activity throughout the obstructive event, although occurring, were not sufficient to restore flow without arousal in this instance.

Figure 1.

Polysomnographic tracings of obstructive sleep apnea from a detailed experimental study of a patient with severe disease (apnea–hypopnea index = 56 events/h). EMGgg = Electromyogram of the genioglossus muscle (intramuscular); EMGsub = EMG of the submental muscle (surface); EEG = electroencephalogram (C3–A2); Pepi = pressure at the level of the epiglottis; Flow = airflow measured via nasal mask and pneumotachograph; Sa_O2 = arterial blood oxygen saturation measured via pulse oximetry at the finger. (A) An 8-minute segment during stage 2 sleep, during which the patient is experiencing sleep-disordered breathing. Note the repeated oxygen desaturations as a result of severely impaired (hypopnea) or absent (apnea) airflow despite continual breathing efforts (Pepi) and the cyclical breathing pattern that ensues as the patient oscillates between sleep and arousal (downward pointing arrows). (B) An expanded segment during an obstructive event. Note: Evidence of snoring on the flow tracing, quantification of the arousal threshold, and progressive increases in EMGgg activity throughout the obstructive event, although occurring, were not sufficient to restore flow without arousal in this instance.

Figure 2.

(A) Schematic representation of the typical pathophysiological sequence that occurs in obstructive sleep apnea (OSA) (shown in gray) and the associated physiological processes that occur throughout the cycle that are either protective/restorative (outside the circle) or perpetuating (inside the circle). UA = upper airway. (B) Schematic representation of the possible sites where each of the various pathophysiological traits would either predispose or tend to worsen OSA (inside the main circle). Note that some of the effects of these traits may be interrelated (i.e., a high loop gain may increase the ventilatory response to arousal and the propensity for cyclical breathing, and also lead to periods of decreased upper airway dilator muscle activity). Refer to the text for further detail. Some of the potential factors that may alleviate OSA at various points throughout the typical physiological cycle (dashed arrows and ovals) are located outside the main circle. Note that some factors are theoretical and largely untested whereas others are more proven therapies (i.e., continuous positive airway pressure [CPAP]).

Figure 2.

(A) Schematic representation of the typical pathophysiological sequence that occurs in obstructive sleep apnea (OSA) (shown in gray) and the associated physiological processes that occur throughout the cycle that are either protective/restorative (outside the circle) or perpetuating (inside the circle). UA = upper airway. (B) Schematic representation of the possible sites where each of the various pathophysiological traits would either predispose or tend to worsen OSA (inside the main circle). Note that some of the effects of these traits may be interrelated (i.e., a high loop gain may increase the ventilatory response to arousal and the propensity for cyclical breathing, and also lead to periods of decreased upper airway dilator muscle activity). Refer to the text for further detail. Some of the potential factors that may alleviate OSA at various points throughout the typical physiological cycle (dashed arrows and ovals) are located outside the main circle. Note that some factors are theoretical and largely untested whereas others are more proven therapies (i.e., continuous positive airway pressure [CPAP]).