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 in-lab or home sleep studies.
“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]
The Discussion (page unavailable) says loop gain can be quantified from routine clinical polysomnography, and Methodological considerations specifies that the study used data from an in-laboratory clinical environment. Our copy does not establish that the method works with home sleep studies, so the home-study part of the claim is unsupported by this source. (LLM, conf=0.86)
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From CPAP to tailored therapy for obstructive sleep Apnoea
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Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep stage dependent
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Self-citationSleep disturbance as a therapeutic target to improve opioid use disorder treatment.
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Non-REM Apnea and Hypopnea Duration Varies across Population Groups and Physiologic Traits
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Self-citationNeural ventilatory drive decline as a predominant mechanism of obstructive sleep apnoea events
Gell, L. K., Vena, D., Alex, R. M., Azarbarzin, A., Calianese, N. A., Hess, L. B., Taranto‐Montemurro, L., White, D. P., Wellman, A., & Sands, S. A. (2022) · Thorax · doi:10.1136/thoraxjnl-2021-217756 · Cited by 53 · see citing works
Self-citationO’Driscoll, D. M., Landry, S. A., Pham, J., Young, A. C., Sands, S. A., Hamilton, G. S., & Edwards, B. A. (2019) · SLEEP · doi:10.1093/sleep/zsz186 · Cited by 51 · see citing works
Self-citationPrecision Medicine for Obstructive Sleep Apnea
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Self-citationThe role of artificial intelligence in the treatment of obstructive sleep apnea
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea
Li, Y., Ye, J., Han, D., Zhao, D., Cao, X., Orr, J., Jen, R., Deacon-Diaz, N., Sands, S. A., Owens, R., et al. (2019) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7848 · Cited by 38 · see citing works
Self-citationMandibular Advancement Devices for OSA: An Alternative to CPAP?
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Self-citationDaytime loop gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment
Deacon-Diaz, N. L., Sands, S. A., McEvoy, R. D., & Catcheside, P. G. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00175.2018 · Cited by 37 · see citing works
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Self-citationAwake Multimodal Phenotyping for Prediction of Oral Appliance Treatment Outcome
Sutherland, K., Chan, A. S. L., Ngiam, J., Dalci, O., Darendeliler, M. A., & Cistulli, P. A. (2018) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7484 · Cited by 35 · see citing works
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Vulnerability to Postoperative Complications in Obstructive Sleep Apnea: Importance of Phenotypes
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Self-citationThe importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy
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Prediction in obstructive sleep apnoea: diagnosis, comorbidity risk, and treatment outcomes
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Modification of Endotypic Traits in OSA by the Carbonic Anhydrase Inhibitor Sulthiame
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Self-citationObstructive sleep apnea diagnosis and beyond using portable monitors
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OSA Endotypes: What Are They and What Are Their Potential Clinical Implications?
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Measuring Loop Gain via Home Sleep Testing in Patients with Obstructive Sleep Apnea
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Role of precision medicine in obstructive sleep apnoea
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Advanced polysomnographic analysis for OSA: A pathway to personalized management?
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Self-citationReview and perspective on sleep-disordered breathing research and translation to clinics
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Self-citationIncreased ventilatory variability and complexity in patients with hyperventilation disorder
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Self-citationResonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure
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Self-citationNew Approaches to Diagnosing Sleep-Disordered Breathing
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Self-citation
- 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 › 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
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