Pathophysiology & genetics of obstructive sleep apnoea

Abstract

Obstructive sleep apnoea (OSA) is a highly prevalent condition with proven neurocognitive and cardiovascular consequences. OSA patients experience repetitive narrowing or collapse of the pharyngeal airway during sleep. Multiple factors likely underlie the pathophysiology of this condition with considerable inter-individual variation. Important risk factors for OSA include obesity, male gender, and ageing. However, the mechanisms underlying these major risk factors are not well understood. We briefly review the state-of-the-art knowledge regarding OSA pathogenesis in adults and highlight the potential role of genetics in influencing key OSA pathophysiological traits.

Fig. 1

The role of UADM (upper airway dilator muscles) in stabilizing breathing. Negative intrathoracic pressure plus CO₂ can activate UADM, but negative pressure can also trigger arousal. A hypnotic could potentially change the arousal threshold to stabilize breathing and potentially prevent the consequences of repetitive arousal.

Fig. 2

The double edged sword of arousal leading to both airway opening and possible cardiovascular consequences. Airway opening can be achieved without arousal by activating genioglossus (EMG_GG) through negative pressure plus CO₂.

Fig. 3

Example polysomnographic tracings of an obstructive sleep apnoea event induced by reducing continuous positive airway pressure (from therapeutic to 2cmH₂O) in a 52 yr old male patient with severe OSA (apnoea/hypopnea index= 34.5 events per hour). EMGgg= Electromyogram of the genioglossus muscle (intramuscular), EEG= electroencephalogram (C3-A2), Pepi= pressure at the level of the epiglottis, Pmask= pressure measured via nasal mask, Vt = tidal volume and flow measured via nasal mask and pneumotachograph. There was increased EMGgg activity during the apnoeic event, though it was not significant enough to restore flow without arousal. The arousal threshold is characterized using Pepi, and after arousal there is a large ventilatory response.