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Loop gain predicts residual sleep apnoea among people using positive airway pressure

Eschbach, Erin ; Kushida, Clete ; Peker, Yuksel LU ; Chu, Jen Hwa ; Xu, Zhichao ; Lin, Hung Mo ; Xu, Yunshan ; Azarbarzin, Ali ; Wellman, Andrew and Yaggi, H. Klar , et al. (2026) In Thorax 81(7). p.694-701
Abstract

Rationale: Residual sleep apnoea—defined by an Apnoea-Hypopnoea Index ≥10 events/hour—affects~20% of obstructive sleep apnoea patients treated with positive airway pressure therapy and poses a major clinical challenge. Ventilatory control instability is a plausible cause of residual sleep apnoea. Elevated loop gain (LG), a measure of ventilatory instability, may be a risk factor, but this has not been rigorously tested. Objective: To assess whether high LG at baseline is associated with residual sleep apnoea on positive airway pressure therapy in two large, randomised control trials: Apnoea Positive Pressure Long-Term Efficacy Study (APPLES) and Randomised Intervention with CPAP in Coronary Artery Disease and OSA (RICCADSA). Methods: LG... (More)

Rationale: Residual sleep apnoea—defined by an Apnoea-Hypopnoea Index ≥10 events/hour—affects~20% of obstructive sleep apnoea patients treated with positive airway pressure therapy and poses a major clinical challenge. Ventilatory control instability is a plausible cause of residual sleep apnoea. Elevated loop gain (LG), a measure of ventilatory instability, may be a risk factor, but this has not been rigorously tested. Objective: To assess whether high LG at baseline is associated with residual sleep apnoea on positive airway pressure therapy in two large, randomised control trials: Apnoea Positive Pressure Long-Term Efficacy Study (APPLES) and Randomised Intervention with CPAP in Coronary Artery Disease and OSA (RICCADSA). Methods: LG was estimated from baseline polysomnography using a validated method. Residual sleep apnoea was defined using polysomnography on positive airway pressure at 2 months (APPLES) or device downloads at 3 months (RICCADSA). Logistic regression estimated the odds of residual sleep apnoea with high LG (highest quartile), adjusting for confounders. A sensitivity analysis was performed using linear regression, where both the exposure and outcome were defined continuously. Measurements and main results: In the unadjusted analysis, high LG was associated with threefold odds of residual sleep apnoea in both samples. After adjustment, elevated odds persisted in both APPLES (2.17 (1.24–3.78)) and RICCADSA (3.31 (1.33–8.24)). Associations remained after accounting for measures of central sleep apnoea. Linear regression confirmed the association of LG and residual Apnoea-Hypopnoea Index. Conclusions: High LG is a significant risk factor for residual sleep apnoea on positive airway pressure therapy. Ventilatory control instability identified at baseline may warrant closer monitoring or the initiation of adjunctive therapies aimed at reducing LG and improving the therapeutic response.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lung Physiology, Polysomnography, Respiratory Measurement, Sleep, Sleep apnoea
in
Thorax
volume
81
issue
7
pages
8 pages
publisher
BMJ Publishing Group
external identifiers
  • pmid:41741209
  • scopus:105041788870
ISSN
0040-6376
DOI
10.1136/thorax-2025-223878
language
English
LU publication?
yes
id
3c312e9a-1de3-4ec4-b8f7-e7a9c3a8b928
date added to LUP
2026-09-02 12:11:41
date last changed
2026-09-03 03:00:07
@article{3c312e9a-1de3-4ec4-b8f7-e7a9c3a8b928,
  abstract     = {{<p>Rationale: Residual sleep apnoea—defined by an Apnoea-Hypopnoea Index ≥10 events/hour—affects~20% of obstructive sleep apnoea patients treated with positive airway pressure therapy and poses a major clinical challenge. Ventilatory control instability is a plausible cause of residual sleep apnoea. Elevated loop gain (LG), a measure of ventilatory instability, may be a risk factor, but this has not been rigorously tested. Objective: To assess whether high LG at baseline is associated with residual sleep apnoea on positive airway pressure therapy in two large, randomised control trials: Apnoea Positive Pressure Long-Term Efficacy Study (APPLES) and Randomised Intervention with CPAP in Coronary Artery Disease and OSA (RICCADSA). Methods: LG was estimated from baseline polysomnography using a validated method. Residual sleep apnoea was defined using polysomnography on positive airway pressure at 2 months (APPLES) or device downloads at 3 months (RICCADSA). Logistic regression estimated the odds of residual sleep apnoea with high LG (highest quartile), adjusting for confounders. A sensitivity analysis was performed using linear regression, where both the exposure and outcome were defined continuously. Measurements and main results: In the unadjusted analysis, high LG was associated with threefold odds of residual sleep apnoea in both samples. After adjustment, elevated odds persisted in both APPLES (2.17 (1.24–3.78)) and RICCADSA (3.31 (1.33–8.24)). Associations remained after accounting for measures of central sleep apnoea. Linear regression confirmed the association of LG and residual Apnoea-Hypopnoea Index. Conclusions: High LG is a significant risk factor for residual sleep apnoea on positive airway pressure therapy. Ventilatory control instability identified at baseline may warrant closer monitoring or the initiation of adjunctive therapies aimed at reducing LG and improving the therapeutic response.</p>}},
  author       = {{Eschbach, Erin and Kushida, Clete and Peker, Yuksel and Chu, Jen Hwa and Xu, Zhichao and Lin, Hung Mo and Xu, Yunshan and Azarbarzin, Ali and Wellman, Andrew and Yaggi, H. Klar and Sands, Scott and Zinchuk, Andrey}},
  issn         = {{0040-6376}},
  keywords     = {{Lung Physiology; Polysomnography; Respiratory Measurement; Sleep; Sleep apnoea}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{694--701}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Thorax}},
  title        = {{Loop gain predicts residual sleep apnoea among people using positive airway pressure}},
  url          = {{http://dx.doi.org/10.1136/thorax-2025-223878}},
  doi          = {{10.1136/thorax-2025-223878}},
  volume       = {{81}},
  year         = {{2026}},
}