Oxygen, carbon dioxide, and nitric oxide: role in the pathophysiology of obstructive sleep apnea

Obstructive sleep apnea is a prevalent sleep-related breathing disorder with recurrent episodes of upper airway collapse during sleep, leading to cyclic blood gas fluctuations. Oxygen, carbon dioxide, and nitric oxide play a crucial role in the pathophysiology. This narrative review aims to explore the role of gases in obstructive sleep apnea pathophysiology, focusing on the molecular pathways and effects of chronic intermittent hypoxia, intermittent hypercapnia, and nitric oxide dysregulation. Chronic intermittent hypoxia stimulates molecular pathways such as hypoxia-inducible factor-1α and inflammatory cascades such as nuclear factor kappa B, leading to oxidative stress, endothelial dysfunction, and sympathetic overactivation. Intermittent hypercapnia impacts on chemoreflex sensitivity, ventilatory instability, and autonomic function, with emerging evidence of both pathogenic and potentially beneficial effects. Nitric oxide, which modulates airway tone, vascular reactivity, and immune control, presents a reduced bioavailability in patients with obstructive sleep apnea. These three gas mediators contribute to the complex pathophysiology of obstructive sleep apnea and underlie the long-term cardiovascular, metabolic, and neurocognitive risks of obstructive sleep apnea. Appropriately prioritizing the relationship between these gases and the pathophysiology of obstructive sleep apnea contributes to a new understanding of the disease and new treatment approaches in the future.