Abstract
Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain.
Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide.
Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28; r=0.63, p<0.001), detected the known reduction in loop gain with oxygen (n=11; mean±sem change in loop gain (ΔLG) −0.23±0.08, p=0.02) and acetazolamide (n=11; ΔLG −0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy.
We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control.
Abstract
Ventilatory instability can be measured by clinical polysomnography to guide nonanatomical sleep apnoea therapy http://ow.ly/AyXT3
Footnotes
This article has supplementary material available from erj.ersjournals.com
Support statement: This work was supported by the US National Institutes of Health (grants 5R01HL048531-16, 1R01HL090897-01A2, 1K24HL093218-01A1 and 1P01HL095491) and a National Health and Medical Research Council of Australia (NHMRC) project grant (1064163). S.A. Sands was supported by an American Heart Association Postdoctoral Fellowship 11POST7360012 and is currently supported by a NHMRC C.J. Martin Fellowship (1053201) and R.G. Menzies award. B.A. Edwards is supported by the NHMRC C.J. Martin Fellowship (1035115). D.J. Eckert is supported by a NHMRC R.D. Wright Fellowship (1049814).
Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com
- Received April 2, 2014.
- Accepted August 14, 2014.
- Copyright ©ERS 2015