Breathing and sleep at high altitude

• Ventilatory acclimatization to altitude involves cellular and neurochemical re-organization in the peripheral chemoreceptors and CNS.
• Sleep at high altitude is disturbed by various factors, but principally by periodic breathing (PB).
• The extent of PB during sleep at altitude intensifies with duration and severity of exposure and is explained in part by elevations in loop gain.
• Because PB may elevate rather than reduce mean SaO2 during sleep this may represent an adaptive rather than maladaptive response.
• Although new mechanical and pharmacological means are emerging, oral acetazolamide remains the most effective and practical means to reduce PB.

We provide an updated review on the current understanding of breathing and sleep at high altitude in humans. We conclude that: (1) progressive changes in pH initiated by the respiratory alkalosis do not underlie early (<48 h) ventilatory acclimatization to hypoxia (VAH) because this still proceeds in the absence of such alkalosis; (2) for VAH of longer duration (>48 h), complex cellular and neurochemical re-organization occurs both in the peripheral chemoreceptors as well as within the central nervous system. The latter is likely influenced by central acid-base changes secondary to the extent of the initial respiratory responses to initial exposure to high altitude; (3) sleep at high altitude is disturbed by various factors, but principally by periodic breathing; (4) the extent of periodic breathing during sleep at altitude intensifies with duration and severity of exposure; (5) complex interactions between hypoxic-induced enhancement in peripheral and central chemoreflexes and cerebral blood flow – leading to higher loop gain and breathing instability – underpin this development of periodic breathing during sleep; (6) because periodic breathing may elevate rather than reduce mean SaO2 during sleep, this may represent an adaptive rather than maladaptive response; (7) although oral acetazolamide is an effective means to reduce periodic breathing by 50–80%, recent studies using positive airway pressure devices to increase dead space, hyponotics and theophylline are emerging but appear less practical and effective compared to acetazolamide. Finally, we suggest avenues for future research, and discuss implications for understanding sleep pathology.