A randomized controlled trial assessing the combined effect of acetazolamide and oxygen therapy as a novel treatment for sleep apnoea.

None listed

Recent evidence suggests that obstructive sleep apnoea (OSA) is a multifactorial disorder and is not only the result of a small, collapsible upper airway anatomy. Several non-anatomical physiological traits have been identified that can also play an important role in causing OSA. These include: (1) an oversensitive ventilatory control system (i.e. ventilatory control instability or high loop gain), (2) poor pharyngeal muscle responsiveness, and (3) a low respiratory arousal threshold. Importantly, the relative contribution of each of these traits varies between patients. Thus patients often have OSA for different reasons. An oversensitive ventilatory control system also referred to as having “high loop gain” has been shown to contribute to OSA severity in at least one third of patients. Loop gain characterises the sensitivity of the control of breathing during sleep. Patients with high loop gain have an overly large compensatory respiratory response to any given disturbance in breathing. In such patients, even a mild disturbance to breathing (i.e. hypopnoea) during sleep can produce a self-sustaining unstable breathing pattern, leading to repetitive airway collapse. While singular therapies targeted towards lowering loop gain have shown promise—including oxygen therapy and respiratory stimulants such as the drug acetazolamide (ACZ),— their effect size on reducing loop gain has not been large enough to resolve OSA in the majority of patients studied. Importantly, physiological studies have shown that oxygen and ACZ manipulate different sub-components of the respiratory control system; oxygen reduces ‘controller gain’ whereas ACZ reduces ‘plant gain’. That is, according to respiratory control theory, both of these treatments should have an independent and additive effect on lowering loop gain. As yet no study has assessed the therapeutic effect of manipulating loop gain with a combination of both agents. Importantly, in a sub-group of OSA patients where loop gain is abnormally high (36%), a large reduction in loop gain, is likely to be sufficient to resolve their OSA. The primary purpose of this clinical trial is to assess, for the first time, the ability of the combination of oxygen therapy and ACZ to reduce loop gain and thereby reduce OSA severity. We expect that this combination of therapeutic agents to have a greater effect on lowering loop gain than either alone. As a secondary objective of this trial, we intend to measure, at baseline, each of the four known traits known to cause OSA (upper airway collapsibility, loop gain, pharyngeal muscle responsiveness and respiratory arousal threshold) so that we can determine the characteristics of individuals that demonstrate that greatest therapeutic benefit from this combination therapy.

No related papers found yet.