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Scott A Sands - One of the best experts on this subject based on the ideXlab platform.
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Effect of hypopnea scoring criteria on non-invasive assessment of Loop Gain and surgical outcome prediction
Annals of the American Thoracic Society, 2020Co-Authors: Shane A. Landry, Scott A Sands, Simon A. Joosten, L. Thomson, Anthony Turton, Ai-ming Wong, Paul Leong, Philip I. Terrill, D. Mann, Garun S. HamiltonAbstract:Rationale: Unstable ventilatory control (high Loop Gain) is a causal factor in the development of obstructive sleep apnea. Methods for quantifying Loop Gain using polysomnography have been develope...
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Jeremy Orr, Rachel Jen, Scott A Sands, Robert OwensAbstract:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OSA who have failed positive airway pressure therapy and who are thought to have anatomical predisposition to OSA. We hypothesized that high Loop Gain would decrease following surgical treatment of OSA due to reduced sleep apnea severity. Polysomnography was performed preoperatively and postoperatively to assess OSA severity in 30 Chinese participants who underwent upper airway surgery. Loop Gain was calculated using a validated clinically-applicable method by fitting a feedback control model to airflow. Patients were followed up for a median (interquartile range) of 130 (62, 224) days after surgery. Apnea-hypopnea index (AHI) changed from 60.8 (33.7, 71.7) to 18.4 (9.9, 42.5) events/h (P < .001). Preoperative and postoperative Loop Gain was 0.70 (0.58, 0.80) and 0.53 (0.46, 0.63) respectively (P < .001). There was a positive association between the decrease in Loop Gain and the improvement of AHI (P = .025). High Loop Gain was reduced by surgical treatment of OSA in our cohort. These data suggest that elevated Loop Gain may be acquired in OSA and may provide mechanistic insight into improvement in OSA with upper airway surgery. Registry: ClinicalTrials.gov, Title: The Impact of Sleep Apnea Treatment on Physiology Traits in Chinese Patients With Obstructive Sleep Apnea, Identifier: NCT02696629, URL: https://clinicaltrials.gov/show/NCT02696629. © 2019 American Academy of Sleep Medicine.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of Clinical Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Rachel Jen, Scott A Sands, Jeremy E. Orr, Robert L. OwensAbstract:Study Objectives:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OS...
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breath holding as a means to estimate the Loop Gain contribution to obstructive sleep apnoea
The Journal of Physiology, 2018Co-Authors: Andrew Wellman, Ludovico Messineo, Ali Azarbarzin, Melania Marques, N. Calianese, David P. White, Luigi Tarantomontemurro, Scott A SandsAbstract:KEY POINTS A hypersensitive ventilatory control system or elevated "Loop Gain" during sleep is a primary phenotypic trait causing obstructive sleep apnoea (OSA). Despite the multitude of methods available to assess the anatomical contributions to OSA during wakefulness in the clinical setting (e.g. neck circumference, pharyngometry, Mallampati score), it is currently not possible to recognize elevated Loop Gain in patients in this context. Loop Gain during sleep can now be recognized using simplified testing during wakefulness, specifically in the form of a reduced maximal breath-hold duration, or a larger ventilatory response to voluntary 20-second breath-holds. We consider that easy breath-holding manoeuvres will enable daytime recognition of a high Loop Gain in OSA for more personalized intervention. ABSTRACT Increased "Loop Gain" of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring Loop Gain in the clinical setting are lacking. Here we test the hypothesis that elevated Loop Gain during sleep can be recognized using voluntary breath-hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath-holding manoeuvres performed during wakefulness. We assessed (1) maximal breath-hold duration, and (2) the ventilatory response to 20 s breath-holds. For comparison, gold standard Loop Gain values were obtained during non-rapid eye movement (non-REM) sleep using the ventilatory response to 20 s pulses of hypoxic-hypercapnic gas (6% CO2 -14% O2 , mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard Loop Gain measurement during wakefulness and steady-state Loop Gain measurement during sleep using CPAP dial-ups. Higher Loop Gain during sleep was associated with (1) a shorter maximal breath-hold duration (r2 = 0.49, P < 0.001), and (2) a larger ventilatory response to 20 s breath-holds during wakefulness (second breath; r2 = 0.50, P < 0.001); together these factors combine to predict high Loop Gain (receiver operating characteristic area-under-curve: 92%). Gold standard Loop Gain values were remarkably similar during wake and non-REM sleep. The results show that elevated Loop Gain during sleep can be identified using simple breath-holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment.
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Daytime Loop Gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment.
Journal of applied physiology (Bethesda Md. : 1985), 2018Co-Authors: Naomi Deacon-diaz, Scott A Sands, R. Doug Mcevoy, Peter CatchesideAbstract: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 inc...
Naomi Deacon-diaz - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Jeremy Orr, Rachel Jen, Scott A Sands, Robert OwensAbstract:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OSA who have failed positive airway pressure therapy and who are thought to have anatomical predisposition to OSA. We hypothesized that high Loop Gain would decrease following surgical treatment of OSA due to reduced sleep apnea severity. Polysomnography was performed preoperatively and postoperatively to assess OSA severity in 30 Chinese participants who underwent upper airway surgery. Loop Gain was calculated using a validated clinically-applicable method by fitting a feedback control model to airflow. Patients were followed up for a median (interquartile range) of 130 (62, 224) days after surgery. Apnea-hypopnea index (AHI) changed from 60.8 (33.7, 71.7) to 18.4 (9.9, 42.5) events/h (P < .001). Preoperative and postoperative Loop Gain was 0.70 (0.58, 0.80) and 0.53 (0.46, 0.63) respectively (P < .001). There was a positive association between the decrease in Loop Gain and the improvement of AHI (P = .025). High Loop Gain was reduced by surgical treatment of OSA in our cohort. These data suggest that elevated Loop Gain may be acquired in OSA and may provide mechanistic insight into improvement in OSA with upper airway surgery. Registry: ClinicalTrials.gov, Title: The Impact of Sleep Apnea Treatment on Physiology Traits in Chinese Patients With Obstructive Sleep Apnea, Identifier: NCT02696629, URL: https://clinicaltrials.gov/show/NCT02696629. © 2019 American Academy of Sleep Medicine.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of Clinical Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Rachel Jen, Scott A Sands, Jeremy E. Orr, Robert L. OwensAbstract:Study Objectives:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OS...
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Inherent vs. Induced Loop Gain Abnormalities in Obstructive Sleep Apnea.
Frontiers in neurology, 2018Co-Authors: Naomi Deacon-diaz, Atul MalhotraAbstract:Unstable ventilatory chemoreflex control, quantified as Loop Gain, is recognized as one of four key pathophysiological traits that contribute to cause obstructive sleep apnea (OSA). Novel treatments aimed at reducing Loop Gain are being investigated, with the intention that future OSA treatment may be tailored to the individual's specific cause of apnea. However, few studies have evaluated Loop Gain in OSA and non-OSA controls and those that have provide little evidence to support an inherent abnormality in either overall chemical Loop Gain in OSA patients vs. non-OSA controls, or its components (controller and plant Gain). However, intermittent hypoxia may induce high controller Gain through neuroplastic changes to chemoreflex control, and may also decrease plant Gain via oxidative stress induced inflammation and reduced lung function. The inherent difficulties and limitations with Loop Gain measurements are discussed and areas where further research are required are highlighted, as only by understanding the mechanisms underlying OSA are new therapeutic approaches likely to emerge in OSA.
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Daytime Loop Gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment.
Journal of applied physiology (Bethesda Md. : 1985), 2018Co-Authors: Naomi Deacon-diaz, Scott A Sands, R. Doug Mcevoy, Peter CatchesideAbstract: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 inc...
Robert L. Owens - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of Clinical Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Rachel Jen, Scott A Sands, Jeremy E. Orr, Robert L. OwensAbstract:Study Objectives:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OS...
Atul Malhotra - One of the best experts on this subject based on the ideXlab platform.
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Inherent vs. Induced Loop Gain Abnormalities in Obstructive Sleep Apnea.
Frontiers in neurology, 2018Co-Authors: Naomi Deacon-diaz, Atul MalhotraAbstract:Unstable ventilatory chemoreflex control, quantified as Loop Gain, is recognized as one of four key pathophysiological traits that contribute to cause obstructive sleep apnea (OSA). Novel treatments aimed at reducing Loop Gain are being investigated, with the intention that future OSA treatment may be tailored to the individual's specific cause of apnea. However, few studies have evaluated Loop Gain in OSA and non-OSA controls and those that have provide little evidence to support an inherent abnormality in either overall chemical Loop Gain in OSA patients vs. non-OSA controls, or its components (controller and plant Gain). However, intermittent hypoxia may induce high controller Gain through neuroplastic changes to chemoreflex control, and may also decrease plant Gain via oxidative stress induced inflammation and reduced lung function. The inherent difficulties and limitations with Loop Gain measurements are discussed and areas where further research are required are highlighted, as only by understanding the mechanisms underlying OSA are new therapeutic approaches likely to emerge in OSA.
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Model-based estimation of Loop Gain using spontaneous breathing: A validation study
Respiratory physiology & neurobiology, 2014Co-Authors: Elnaz Gederi, Atul Malhotra, Shamim Nemati, Bradley A. Edwards, Gari D. Clifford, Andrew WellmanAbstract:a b s t r a c t Non-invasive assessment of ventilatory control stability or Loop Gain (which is a key contributor in a num- ber of sleep-related breathing disorders) has proven to be cumbersome. We present a novel multivariate autoregressive model that we hypothesize will enable us to make time-varying measurements of Loop Gain using nothing more than spontaneous fluctuations in ventilation and CO2. The model is adaptive to changes in the feedback control Loop and therefore can account for system non-stationarities (e.g. changes in sleep state) and it is resistant to artifacts by using a signal quality measure. We tested this method by assessing its ability to detect a known increase in Loop Gain induced by proportional assist ventilation (PAV). Subjects were studied during sleep while breathing on continuous positive airway pressure (CPAP) alone (to stabilize the airway) or on CPAP + PAV. We show that the method tracked the PAV-induced increase in Loop Gain, demonstrating its time-varying capabilities, and it remained accu- rate in the face of measurement related artifacts. The model was able to detect a statistically significant increase in Loop Gain from 0.14 ± 10 on CPAP alone to 0.21 ± 0.13 on CPAP + PAV (p < 0.05). Furthermore, our method correctly detected that the PAV-induced increase in Loop Gain was predominantly driven by an increase in controller Gain. Taken together, these data provide compelling evidence for the validity of this technique.
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CrossTalk opposing view: Loop Gain is not a consequence of obstructive sleep apnoea
The Journal of physiology, 2014Co-Authors: Jeremy E. Orr, Bradley A. Edwards, Atul MalhotraAbstract:J Physiol 592.14 (2014) pp 2903–2905 C R O S S TA L K CrossTalk opposing view: Loop Gain is not a consequence of obstructive sleep apnoea J. E. Orr 1 , B. A. Edwards 2 and A. Malhotra 1,2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA, USA Division of Sleep Medicine, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA, USA The Journal of Physiology Email: j1orr@ucsd.edu Obstructive sleep apnoea (OSA) is a common disease affecting at least 13% of adult men and 6% of adult women in the United States (Peppard et al. 2013) and is characterized by repetitive collapse (apnoea) or partial collapse (hypopnoea) of the pharyngeal airway during sleep (Sullivan & Issa, 1985; Guilleminault et al. 1986; Young et al. 1993; Hamilton et al. 2004). Recent studies suggest that OSA is a multifactorial condition, and not just an anatomical problem (Wellman et al. 2011; Eckert et al. 2013). Alongside anatomical vulnerability, at least three additional physiological traits interact to contribute to the development of OSA including (1) ineffective upper airway dilator muscles, (2) a low threshold for arousal from sleep, and (3) a hypersensitive ventilatory control system (i.e. high Loop Gain) (Dempsey et al. 2010). In individual patients, the manifestation of OSA may be the result of one or more combinations of abnormalities, and thus multiple underlying causes may need to be addressed for sleep apnoea to be resolved. Interestingly, recent evidence has questioned whether some of these traits such as a high Loop Gain are truly pathogenic (i.e. an intrinsic cause of OSA) or merely reflect a consequence of the disorder. Loop Gain characterizes the sensitivity of the negative feedback system controlling ventilation and is defined as the size of a ‘corrective’ ventilatory response divided by the size of the ventilatory disturbance that elicits the correction (see Fig. 1); a large response to a small disturbance represents a system with a high Loop Gain. In favour of an elevated Loop Gain being an acquired condition (i.e. a consequence of disease) are two investigations whose findings demonstrate that treatment of OSA leads to major reductions in Loop Gain. Salloum et al. examined the effect of one month of nasal continuous positive airway pressure (CPAP) therapy on the components of the ventilatory control system – plant and controller Gain – in a group of recently diagnosed and untreated severe OSA patients (Salloum et al. 2010). They reported that one month of treatment led to reductions in the ventilatory sensitivity to CO 2 (i.e. controller Gain), and thus Loop Gain (as plant Gain remained unchanged), back to levels similar to healthy controls. In another study, Loewen et al. measured the dynamic ventilatory response to CO 2 in a group of severe OSA patients before and after one month of CPAP therapy (Loewen et al. 2009). Similar to the study by Salloum et al., Loewen et al. observed that ventilatory sensitivity to CO 2 was markedly diminished following CPAP therapy; taken together, such findings seem to suggest that a high Loop Gain is a consequence of OSA. However, we would argue that the findings of these two investigations do not provide conclusive evidence that an elevated Loop Gain is solely a consequence of OSA. An important implication of the aforementioned studies is that one month of effective treatment was sufficient to reverse the consequences of disease and allowed an individual’s ‘intrinsic’ physiology to be assessed. However, studies that have manipulated Loop Gain in CPAP-treated OSA patients have consistently shown that lowering the ‘intrinsic’ Loop Gain is associated with an improvement in OSA severity, highlighting the importance of Loop Gain as a cause of OSA. For instance, administration of oxygen, which is known to lower Loop Gain via reductions in controller Gain, led to marked improvement in OSA among those patients with elevated Loop Gain at baseline (Wellman et al. 2008; Chowdhuri et al. 2010). No such improvement was observed in patients with low Loop Gain, highlighting that the intrinsic elevation in Loop Gain (at baseline) was pathophysiologically important in some OSA patients. In addition to oxygen therapy, the administration of acetazolamide has also been shown to lower Loop Gain and OSA severity (Edwards et al. 2012, 2013). Furthermore, the use of cardiac resynchronization therapy as a treatment for congestive heart failure additionally improves OSA (Stanchina et al. 2007). In this study, the observed improvement in OSA was strongly correlated with the improvement in circulatory delay, the effect of which is expected to decrease Loop Gain. Elevated Loop Gain may be critical to OSA pathogenesis in some patients, and will likely be dependent on the inter- action with other pathophysiological traits that predispose towards apnoea. Depending on the underlying anatomy, Loop Gain can explain a large proportion of the variance in OSA severity (Wellman et al. 2004; Eckert et al. 2013). Patients with extreme pharyngeal closing pressures (P crit ) were either protected (negative P crit ) or pre- disposed (positive P crit ) to apnoea based on intrinsic anatomy, whereas those with intermediate values were most susceptible to OSA if their Loop Gain was elevated. Jeremy E. Orr (left) is a Fellow in Pulmonary and Critical Care Medicine at the University of California, San Diego. His current research is focused on the interaction between abnormal ventilatory control and circulatory disorders. Bradley A. Edwards (right) is an Instructor in Medicine in Sleep Medicine at the Brigham and Women’s Hospital and Harvard Medical School. His research focuses on understanding the pathogenesis of the common sleep disorder, obstructive sleep apnoea, as well as developing and assessing novel ways to treat the disorder. Atul Malhotra is a Professor of Medicine in Pulmonary and Critical Care Medicine, as well as the director of Sleep Medicine at the University of California, San Diego. C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society DOI: 10.1113/jphysiol.2014.271841
Demin Han - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Jeremy Orr, Rachel Jen, Scott A Sands, Robert OwensAbstract:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OSA who have failed positive airway pressure therapy and who are thought to have anatomical predisposition to OSA. We hypothesized that high Loop Gain would decrease following surgical treatment of OSA due to reduced sleep apnea severity. Polysomnography was performed preoperatively and postoperatively to assess OSA severity in 30 Chinese participants who underwent upper airway surgery. Loop Gain was calculated using a validated clinically-applicable method by fitting a feedback control model to airflow. Patients were followed up for a median (interquartile range) of 130 (62, 224) days after surgery. Apnea-hypopnea index (AHI) changed from 60.8 (33.7, 71.7) to 18.4 (9.9, 42.5) events/h (P < .001). Preoperative and postoperative Loop Gain was 0.70 (0.58, 0.80) and 0.53 (0.46, 0.63) respectively (P < .001). There was a positive association between the decrease in Loop Gain and the improvement of AHI (P = .025). High Loop Gain was reduced by surgical treatment of OSA in our cohort. These data suggest that elevated Loop Gain may be acquired in OSA and may provide mechanistic insight into improvement in OSA with upper airway surgery. Registry: ClinicalTrials.gov, Title: The Impact of Sleep Apnea Treatment on Physiology Traits in Chinese Patients With Obstructive Sleep Apnea, Identifier: NCT02696629, URL: https://clinicaltrials.gov/show/NCT02696629. © 2019 American Academy of Sleep Medicine.
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The Effect of Upper Airway Surgery on Loop Gain in Obstructive Sleep Apnea.
Journal of Clinical Sleep Medicine, 2019Co-Authors: Demin Han, Naomi Deacon-diaz, Di Zhao, Xin Cao, Rachel Jen, Scott A Sands, Jeremy E. Orr, Robert L. OwensAbstract:Study Objectives:Controversy exists as to whether elevated Loop Gain is a cause or consequence of obstructive sleep apnea (OSA). Upper airway surgery is commonly performed in Asian patients with OS...
