Intermittent hypoxia and sleep-disordered breathing: current concepts and perspectives

There are three major types of sleep-disordered breathing (SDB) with respect to prevalence and health consequences, i.e. obstructive sleep apnoea syndrome (OSAS), Cheyne-Stokes respiration and central sleep apnoea (CSR-CSA) in chronic heart failure, and obesity hypoventilation syndrome (OHS). In all three conditions, hypoxia appears to affect body functioning in different ways. Most of the molecular and cellular mechanisms that occur in response to SDB-related hypoxia remain unknown. In OSAS, an inflammatory cascade mainly dependent upon intermittent hypoxia has been described. There is a strong interaction between haemodynamic and inflammatory changes in promoting vascular remodelling. Moreover, during OSAS, most organ, tissue or functional impairment is related to the severity of nocturnal hypoxia. CSR-CSA occurring during heart failure is primarily a consequence of cardiac impairment. CSR-CSA has deleterious consequences for cardiac prognosis and mortality since it favours sympathetic activation, ventricular ectopy and atrial fibrillation. Although correction of CSR-CSA seems to be critical, there is a need to establish therapy guidelines in large randomised controlled trials. Finally, OHS is a growing health concern, owing to the worldwide obesity epidemic and OHS morbidities. The pathophysiology of OHS remains largely unknown. However, resistance to leptin, obesity and severe nocturnal hypoxia lead to insulin resistance and endothelial dysfunction. In addition, several adipokines may be triggered by hypoxia and explain, at least in part, OHS morbidity and mortality. Overall, chronic intermittent hypoxia appears to have specific genomic effects that differ notably from continuous hypoxia. Further research is required to fully elucidate the molecular and cellular mechanisms.