Daytime loop gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment
Open accessAbstract
Reduced ventilatory control stability (elevated loop gain) is a key nonanatomical, pathological trait contributing to obstructive sleep apnea (OSA), yet the mechanisms responsible remain unclear. We sought to identify the key factors contributing to elevated loop gain in OSA (controller vs. plant contributions) and to examine whether abnormalities in these factors persist after OSA treatment. In 15 males (8 OSA, 7 height, weight- and age -matched controls), we measured loop gain, controller gain, and plant gain using a pseudorandom binary CO 2 stimulation method during wakefulness. Factors potentially influencing plant gain were also assessed (supine lung volume via helium dilution and spirometry). Measures were repeated 2 and 6 wk after initiating continuous positive airway pressure treatment. Loop gain (LG) was higher in OSA versus controls (LG at 1 cycle/min 0.28 ± 0.04 vs. 0.16 ± 0.04, P = 0.046, respectively), and the controller exhibited a greater peak response to CO 2 and faster roll-off in OSA. OSA patients also exhibited reduced forced expiratory volume in the first second and forced vital capacity compared with controls (92.2 ± 1.7 vs. 102.9 ± 3.5% predicted, P = 0.021; 93.4 ± 3.1 vs. 106.6 ± 3.6% predicted, P = 0.015, respectively). There was no effect of treatment on any variable. These findings confirm loop gain is higher in untreated OSA patients than in matched controls; however, this was not affected by treatment. NEW & NOTEWORTHY Elevated loop gain contributes to obstructive sleep apnea (OSA) pathophysiology. However, whether loop gain is inherently elevated in OSA or induced by OSA itself, whether it is elevated due to increased chemoreflex sensitivity or obesity-dependent reduced lung volume, and whether it is treatment reversible, are all currently uncertain. This study found loop gain was elevated in OSA versus age-, sex-, height-, and weight-matched controls. However, this was not altered by 6-wk continuous positive airway pressure treatment.
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Breathing dysfunction has been correlated with OSA pathophysiology, specifically with reduced ventilatory control stability and an elevated loop gain, a non-anatomical contributor trait to OSA.
“It has been correlated with OSA pathophysiology, specifically with reduced ventilatory control stability, and an elevated loop gain, 105 a non-anatomical contributor trait to OSA. 106”
From Role of Nasal Surgery in Adult Obstructive Sleep Apnea: A Systematic Review (2024) · cites this paper as [106]
Cites
Determinants of ventilatory instability and variability
Khoo, M. C. K. (2000) · Respiration Physiology · doi:10.1016/s0034-5687(00)00157-2 · Cited by 304 · see citing works
Quantifying the ventilatory control contribution to sleep apnoea using polysomnography
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. (2015) · European Respiratory Journal · doi:10.1183/09031936.00062914 · Cited by 289 · see citing works
Self-citationA method for measuring and modeling the physiological traits causing obstructive sleep apnea
Wellman, A., Eckert, D. J., Jordan, A. S., Edwards, B. A., Passaglia, C. L., Jackson, A. C., Gautam, S., Owens, R. L., Malhotra, A., & White, D. P. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00972.2010 · Cited by 283 · see citing works
A simplified method for determining phenotypic traits in patients with obstructive sleep apnea
Wellman, A., Edwards, B. A., Sands, S. A., Owens, R. L., Nemati, S., Butler, J., Passaglia, C. L., Jackson, A. C., Malhotra, A., & White, D. P. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00747.2012 · Cited by 222 · see citing works
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Inherent vs. Induced Loop Gain Abnormalities in Obstructive Sleep Apnea
Deacon-Diaz, N., & Malhotra, A. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00896 · Cited by 69 · see citing works
Self-citationRole of Nasal Surgery in Adult Obstructive Sleep Apnea: A Systematic Review
Correa, E. J., Conti, D. M., Moreno-Luna, R., Sánchez-Gómez, S., & O'Connor Reina, C. (2024) · Sleep Science · doi:10.1055/s-0044-1782527 · Cited by 15 · see citing works
“106 Although the literature regarding functional breathing evaluation in OSA patients is still scarce, Messineo et al. 107 have published a simpli fi ed breath-holding maneuver to be performed in the of fi ce, demonstrating a strong correlation between ventilatory response during wakefulness and the…”
Background
- Authors
- Deacon-Diaz, N. L., Sands, S. A., McEvoy, R. D., & Catcheside, P. G.
- Affiliations
- Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- Brigham and Women's Hospital (US)
- Flinders University (AU)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2018-11-01
- Volume
- 125
- Issue
- 5
- Pages
- 1490-1497
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- PMC
- PMC6295487
- OpenAlex
- W2889262372
- Cited by
- 37
- References
- 4
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 1
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- American Heart Association (AHA) (15SDG25890059)
- Department of Health, Australian Government | National Health and Medical Research Council (NHMRC) (1053201)
- R.G.Menzies Foundation (R01HL128658)
- American Thoracic Society (ATS) (2R01HL102321)
- National Institute of Health (P01HL10050580)
- Australian Research Council Future Fellowship (FT120100510)
- 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, loop gain, control gain, continuous positive airway pressure, CO2 stimulation, chemoreflex sensitivity, lung volume, lung function
- MeSH terms
- Adult, Humans, Lung, Male, Middle Aged, Respiration, Respiratory Function Tests, Case-Control Studies, Sleep Apnea, Obstructive, Feedback, Physiological, Continuous Positive Airway Pressure
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