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

Area of Science:

• Sleep Medicine
• Cardiology
• Pulmonology
• Endocrinology

Background:

• Sleep-disordered breathing (SDB) encompasses obstructive sleep apnoea syndrome (OSAS), Cheyne-Stokes respiration/central sleep apnoea (CSR-CSA) in heart failure, and obesity hypoventilation syndrome (OHS).
• Hypoxia in SDB affects body function through distinct molecular and cellular pathways.
• The precise mechanisms linking SDB-related hypoxia to organ impairment remain largely unknown.

Purpose of the Study:

• To review the current understanding of the molecular and cellular mechanisms of hypoxia in major SDB types.
• To highlight the health consequences and pathophysiological aspects of OSAS, CSR-CSA, and OHS.
• To identify knowledge gaps and areas for future research in SDB and hypoxia.

Main Methods:

• Literature review and synthesis of existing research on SDB, hypoxia, and related molecular/cellular mechanisms.
• Analysis of the interplay between hypoxia, inflammation, haemodynamics, and organ dysfunction in OSAS.
• Examination of the pathophysiology of CSR-CSA in heart failure and OHS in obesity.

Main Results:

• OSAS involves an inflammatory cascade driven by intermittent hypoxia, interacting with haemodynamic changes to promote vascular remodelling.
• CSR-CSA in heart failure exacerbates cardiac prognosis via sympathetic activation and arrhythmias.
• OHS pathophysiology involves leptin resistance, obesity, and hypoxia leading to insulin resistance and endothelial dysfunction.

Conclusions:

• Chronic intermittent hypoxia has distinct genomic effects compared to continuous hypoxia.
• Further research is crucial to fully elucidate the molecular and cellular mechanisms underlying SDB-related hypoxia.
• Understanding these mechanisms is vital for developing targeted therapies for SDB and its associated morbidities.