Open questions which can be addressed with human hypoxia models
The animal and human models used to study OSA through intermittent
hypoxia induction are inadequate as they do not fully represent all
aspects of the disease [77]. Researchers are therefore seeking
better models to gain a deeper understanding of the underlying
mechanisms. The healthy human model of OSA is continually evolving, with
some limitations that can be resolved through technological adjustments.
To maximize construct validity, experiments should be conducted
overnight on sleeping participants rather than during the waking hours
[78]. Secondly, the intermittent hypoxia model must include
hypercapnia, which is present during obstruction in OSA. Thirdly, the
dose and duration of intermittent hypoxia used in healthy human models
should be equivalent to moderate to severe OSA, with mild to moderate
OSA and equivalent intermittent hypoxia providing beneficial
physiological stimuli [79]. Fourthly, the experimental model’s
intermittent hypoxia should mimic the disease’s characteristic slow
desaturation and rapid re-saturation of oxygen during obstructive
events, as opposed to the current model with a square-wave design of
rapid desaturation and re-saturation. Lastly, full polysomnography is
necessary to characterize sleep architecture, including frequent brain
arousals. The use of dial-down CPAP during sleep can induce upper airway
obstruction and negative intrathoracic pressure swings, thus creating an
experimental model that closely simulates OSA [80]. However, this
technique is labor-intensive, invasive, and risky. The experimental
model for OSA should be tailored to the research question at hand and
may or may not require the complete simulation of OSA.