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

Obstructive sleep apnoea (OSA) is a common disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favours upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of the 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's 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 Apnoea 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 (the Apnoea Hypopnoea Index). The results of the clinical studies indicate that intermittent hypoxia variables are associated with several comorbidities, although evidence of a cause-effect relationship 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.