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

Abstract

There are three major types of sleep-disordered breathing (SDB) with respect to prevalence and health consequences, i.e. obstructive sleep apnoea syndrome (OSAS), CheyneStokes 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.

Sleep Oxygen Desaturation Predicts Survival in Idiopathic Pulmonary Fibrosis

“…27 Furthermore, the desaturation-reoxygenation sequence characterizing intermittent hypoxia constitutes a major stimulus, even more potent than continuous hypoxia, which leads to oxidative stress, systemic inflammation, and generalized vascular endothelial damage adversely affecting myocardial function. 25,28 The present study also shows that SBDs and especially OSA is common in IPF extending previous observations. 2,3 This rate of occurrence is even higher from the 10% of OSA encountered in chronic obstructive pulmonary disease (COPD), rendering the term "overlap" syndrome even more appropriate for the coexistence of OSA and IPF.…”

“…23,24 In this study, both oxygen desaturation indices investigated were correlated with the RVSP measured with Doppler echocardiography, thus providing the link between intermittent oxygen desaturation and pulmonary hypertension as well as its associated mortality. The potential mechanisms linking sleep and exercise oxygen desaturation with the development of PH may relate to different mechanisms, such as the hypoxia-mediated endothelial dysfunction 25 and the rise in arterial endothelin-1 levels-a potent mediator of pulmonary vascular remodelling 26 -as well as to the resetting of peripheral chemoreceptors due to hypoxia and the resulting lowering of the hypoxic drive, which might aggravate sleep oxygen desaturation by delaying arousal. 27 Furthermore, the desaturation-reoxygenation sequence characterizing intermittent hypoxia constitutes a major stimulus, even more potent than continuous hypoxia, which leads to oxidative stress, systemic inflammation, and generalized vascular endothelial damage adversely affecting myocardial function.…”

Association of Cellular Adhesion Molecules and Oxidative Stress with Endothelial Function in Obstructive Sleep Apnea

“…Therefore it is important to study the pathological mechanisms involved in endothelial dysfunction. In this respect, the hallmark of OSA is intermittent hypoxia (20)(21)(22)(23). Our group has described the impact of intermittent hypoxia on the development of endothelial dysfunction (16).…”

“…It is possible that increased oxidative stress worsens endothelial function and increases the release of cellular adhesion molecules. This suggests that both oxidative stress and inflammatory pathways can interact and that endothelial dysfunction is the sum of various causes (5,9,22,23,37,38).…”

Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial

“…Iron has important roles in oxygen metabolism and energy capacity,18 and RLS is often associated with conditions involving hypoxia 19, 20, 21. Notably, baseline TSAT levels correlated significantly with improvement in IRLS scores at week 4 and EOS.…”