Adaptive responses to chronic intermittent hypoxia: contributions from the European Sleep Apnea Cohort (ESADA).

Obstructive sleep apnea (OSA) is a frequent disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favors upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of respiratory drive, and the arousal threshold. OSA causes chronic intermittent hypoxia, inflammatory activation, and autonomic imbalance with diurnal and nocturnal sympathetic hyperactivity. Disentangling so many components to investigate the pathogenesis of OSA consequences is very hard clinically. However, albeit imperfect, clinical medicine constitutes a major source of inspiration for basic research, and a mutual exchange of information is essential between clinicians and physiologists to improve our understanding of disease states. OSA is no exception, and this narrative review will summarize the results of clinical studies performed over the years by the European Sleep Apnea Database (ESADA) Study Group, to explore the variables linked to markers of intermittent hypoxia as opposed to the traditional assessment of OSA severity based on the frequency of respiratory events during sleep (Apnea Hypopnea Index, or AHI). The results of the clinical studies indicate that intermittent hypoxia variables are strongly associated with several comorbidities, although evidence of a cause-effect relationships is still missing in many cases. It is also possible that adaptive rather than maladaptive responses could be evoked by intermittent hypoxia. The intensity, duration and frequency of intermittent hypoxia episodes causing adaptive rather than maladaptive responses, and their clinical implications, deserve further investigation. Abstract figure legend Summary of the current state of knowledge regarding the effects of OSA severity on cardiovascular risk. Mild OSA does not appear to date to affect survival, and some data suggest that mild intermittent hypoxia may exert beneficial effects. On the pther hand, there is plenty of evidence for detrimental effects of severe OSA, possibly mediated by severe intermittent hypoxia. This article is protected by copyright. All rights reserved.