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Quantifying the ventilatory control contribution to sleep apnoea using polysomnography
Open accessAbstract
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.
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“It may be possible to quantify loop gain directly from inlab or home sleep studies.369–371”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [371]
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Metadata
- Authors
- Terrill, P. I., Edwards, B. A., Nemati, S., Butler, J. P., Owens, R. L., Eckert, D. J., White, D. P., Malhotra, A., Wellman, A., & Sands, S. A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Southern California (US)
- ORCID
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2014-10-16
- Volume
- 45
- Issue
- 2
- Pages
- 408-418
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- PMC
- PMC4348093
- OpenAlex
- W2147045852
- Cited by
- 289
- References
- 41
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 29 · 2023: 42 · 2022: 23 · 2021: 20 · 2020: 22 · 2019: 21 · 2018: 23 · 2017: 18 · 2016: 22 · 2015: 8
- FWCI
- 10.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- American Heart Association
- Brigham and Women's Hospital
- National Institutes of Health (1r01hl090897-01a2, 1k24hl093218-01a1)
- Medical Research Council
- National Health and Medical Research Council (1064163, 1035115, 1053201, 1049814)
- National Heart, Lung, and Blood Institute (R01-HL090897, P01HL095491, K24 HL-093218, R01HL085188, 1R01HL090897-01A2, 1K24HL093218-01A1, R01HL048531)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Keywords
- obstructive sleep apnea, ventilation control, loop gain, respiratory drive, polysomnography, arousal, oxygen therapy, acetazolamide, treatment response prediction
- MeSH terms
- Acetazolamide, Adult, Computer Simulation, Female, Humans, Male, Middle Aged, Models, Theoretical, Oscillometry, Oxygen, Patient Compliance, Phenotype, Respiration, Retrospective Studies, Sleep, Polysomnography, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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