Evidence map›Paper›PMID 25323235›Full record

ArticleThe European respiratory journal2015

Quantifying the ventilatory control contribution to sleep apnoea using polysomnography.

Philip I Terrill, Bradley A Edwards, Shamim Nemati, James P Butler, Robert L Owens, Danny J Eckert, David P White, Atul Malhotra, Andrew Wellman, Scott A Sands

2 registry-linked trialsOpen access · bronzeAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The European respiratory journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 164 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed, 3 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02696629 unknown statusnot on this mapstarted 2016, after this paper: background citation

The Impact of Sleep Apnea Treatment on Physiology Traits in Chinese Patients With Obstructive Sleep Apnea

TypeobservationalSponsorBeijing Tongren HospitalRan2016 to 2018Enrolled60ConditionsObstructive Sleep ApneaArmsupper airway surgery, Continues positive airway pressure, education and follow up
NCT07577661 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea: A Randomized-Controlled Trial.

TypeinterventionalSponsorBrigham and Women's HospitalRan2026 to 2027Enrolled24ConditionsObstructive Sleep Apnea, Sleep-disordered BreathingArmsCombination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Placebo, placebo comparator condition
3 · Its place in the literature

Who cites it

164 citing papers in PubMed, 3 syntheses or guidelines pooled it, 269 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2017
    Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Cognitive behavioral therapy for insomnia is associated with reduced sleep apnea severity but not its endotype traits in those with comorbid insomnia and sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025
    Trial
  9. Trial
  10. Trial
  11. Trial
  12. The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023
    Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. A randomized controlled trial of oxygen therapy for patients who do not respond to upper airway surgery for obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2021
    Trial
  18. Trial
  19. Trial
  20. Trial

104 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Philip I TerrillDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.
Bradley A EdwardsDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Shamim NematiDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
James P ButlerDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Robert L OwensDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Danny J EckertDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Neuroscience Research Australia and the School of Medical Sciences, University of New South Wales, Sydney, Australia.
David P WhiteDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Atul MalhotraDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care, University of Southern California San Diego, La Jolla, CA, USA.
Andrew WellmanDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Scott A SandsDivision of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Central Clinical School, The Alfred and Monash University, Melbourne, Australia sasands@partners.org.
Brigham and Women's Hospital · USHarvard University · USUniversity of California, San Diego · USUNSW Sydney · AU

Funding

Wakefulness and Forebrain Activation by Orexin NeuronsP01HL095491 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCAMMELL, THOMAS E · 2010 to 2019
$25.1M
SLEEP, AIRWAY PATENCY, AND THE PHARYNGEAL MUSCULATURER01HL048531 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI WHITE, DAVID P. · 1992 to 2009
$3.8M
Single Motor Unit Genioglossus Recordings to Understand Sleep Apnea PathogenesisR01HL085188 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALHOTRA, ATUL · 2008 to 2018
$3.5M
Mechanisms Underlying the Aging Predisposition to Obstructive Sleep ApneaR01HL090897 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MALHOTRA, ATUL · 2009 to 2012
$1.8M
Assessment of Upper Airway Mechanics Using Newer EMG TechniquesK24HL093218 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALHOTRA, ATUL · 2009 to 2013
$857k
NHLBI NIH HHS 1K24HL093218-01A1NHLBI NIH HHS 1P01HL095491NHLBI NIH HHS 1R01HL090897-01A2NHLBI NIH HHS 5R01HL048531-16NHLBI NIH HHS K24 HL093218NHLBI NIH HHS P01 HL095491NHLBI NIH HHS R01 HL048531NHLBI NIH HHS R01 HL085188NHLBI NIH HHS R01 HL090897
6 · The paper itself

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.

Indexed as

PolysomnographyRespirationAcetazolamideAdultComputer SimulationContinuous Positive Airway PressureFemaleHumansMaleMiddle AgedModels, TheoreticalOscillometryOxygenPatient CompliancePhenotypeRetrospective StudiesAcetazolamideOxygen

Identifiers

PMID25323235
PMCPMC4348093
OpenAlexW2147045852

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.