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https://www.readbyqxmd.com/read/27799387/desipramine-improves-upper-airway-collapsibility-and-reduces-osa-severity-in-patients-with-minimal-muscle-compensation
#1
Luigi Taranto-Montemurro, Scott A Sands, Bradley A Edwards, Ali Azarbarzin, Melania Marques, Camila de Melo, Danny J Eckert, David P White, Andrew Wellman
We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea-hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep...
November 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27634790/the-combination-of-supplemental-oxygen-and-a-hypnotic-markedly-improves-obstructive-sleep-apnea-in-patients-with-a-mild-to-moderate-upper-airway-collapsibility
#2
Bradley A Edwards, Scott A Sands, Robert L Owens, Danny J Eckert, Shane Landry, David P White, Atul Malhotra, Andrew Wellman
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA...
November 1, 2016: Sleep
https://www.readbyqxmd.com/read/27634788/estimation-of-pharyngeal-collapsibility-during-sleep-by-peak-inspiratory-airflow
#3
Ali Azarbarzin, Scott A Sands, Luigi Taranto-Montemurro, Melania D Oliveira Marques, Pedro R Genta, Bradley A Edwards, James Butler, David P White, Andrew Wellman
OBJECTIVES: Pharyngeal critical closing pressure (Pcrit) or collapsibility is a major determinant of obstructive sleep apnea (OSA) and may be used to predict the success/failure of non-continuous positive airway pressure (CPAP) therapies. Since its assessment involves overnight manipulation of CPAP, we sought to validate the peak inspiratory flow during natural sleep (without CPAP) as a simple surrogate measurement of collapsibility. METHODS: Fourteen patients with OSA attended overnight polysomnography with pneumotachograph airflow...
September 9, 2016: Sleep
https://www.readbyqxmd.com/read/27181367/upper-airway-collapsibility-and-loop-gain-predict-the-response-to-oral-appliance-therapy-in-patients-with-obstructive-sleep-apnea
#4
Bradley A Edwards, Christopher Andara, Shane Landry, Scott A Sands, Simon A Joosten, Robert L Owens, David P White, Garun S Hamilton, Andrew Wellman
RATIONALE: Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea-hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. OBJECTIVES: The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy...
December 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26967681/desipramine-increases-genioglossus-activity-and-reduces-upper-airway-collapsibility-during-non-rem-sleep-in-healthy-subjects
#5
Luigi Taranto-Montemurro, Bradley A Edwards, Scott A Sands, Melania Marques, Danny J Eckert, David P White, Andrew Wellman
RATIONALE: Obstructive sleep apnea is a state-dependent disease. One of the key factors that triggers upper airway collapse is decreased pharyngeal dilator muscle activity during sleep. To date, there have not been effective methods to reverse pharyngeal hypotonia pharmacologically in sleeping humans. OBJECTIVES: We tested the hypothesis that administration of desipramine 200 mg prevents the state-related reduction in genioglossus activity that occurs during sleep and thereby decreases pharyngeal collapsibility...
October 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26446124/tube-law-of-the-pharyngeal-airway-in-sleeping-patients-with-obstructive-sleep-apnea
#6
Pedro R Genta, Bradley A Edwards, Scott A Sands, Robert L Owens, James P Butler, Stephen H Loring, David P White, Andrew Wellman
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. However, the dynamics of pharyngeal narrowing and re-expansion during flow-limited breathing are not well described. The static pharyngeal tube law (end-expiratory area versus luminal pressure) has demonstrated increasing pharyngeal compliance as luminal pressure decreases, indicating that the airway would be sucked closed with sufficient inspiratory effort. On the contrary, the airway is rarely sucked closed during inspiratory flow limitation, suggesting that the airway is getting stiffer...
February 1, 2016: Sleep
https://www.readbyqxmd.com/read/25515107/an-integrative-model-of-physiological-traits-can-be-used-to-predict-obstructive-sleep-apnea-and-response-to-non-positive-airway-pressure-therapy
#7
Robert L Owens, Bradley A Edwards, Danny J Eckert, Amy S Jordan, Scott A Sands, Atul Malhotra, David P White, Stephen H Loring, James P Butler, Andrew Wellman
STUDY OBJECTIVES: Both anatomical and nonanatomical traits are important in obstructive sleep apnea (OSA) pathogenesis. We have previously described a model combining these traits, but have not determined its diagnostic accuracy to predict OSA. A valid model, and knowledge of the published effect sizes of trait manipulation, would also allow us to predict the number of patients with OSA who might be effectively treated without using positive airway pressure (PAP). DESIGN, PARTICIPANTS AND INTERVENTION: Fifty-seven subjects with and without OSA underwent standard clinical and research sleep studies to measure OSA severity and the physiological traits important for OSA pathogenesis, respectively...
2015: Sleep
https://www.readbyqxmd.com/read/25324514/test-of-the-starling-resistor-model-in-the-human-upper-airway-during-sleep
#8
Andrew Wellman, Pedro R Genta, Robert L Owens, Bradley A Edwards, Scott A Sands, Stephen H Loring, David P White, Andrew C Jackson, Ole F Pedersen, James P Butler
The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model--that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors...
December 15, 2014: Journal of Applied Physiology
https://www.readbyqxmd.com/read/25323235/quantifying-the-ventilatory-control-contribution-to-sleep-apnoea-using-polysomnography
#9
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
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)...
February 2015: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/25321848/clinical-predictors-of-the-respiratory-arousal-threshold-in-patients-with-obstructive-sleep-apnea
#10
Bradley A Edwards, Danny J Eckert, David G McSharry, Scott A Sands, Amar Desai, Geoffrey Kehlmann, Jessie P Bakker, Pedro R Genta, Robert L Owens, David P White, Andrew Wellman, Atul Malhotra
RATIONALE: A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. OBJECTIVES: To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH. METHODS: Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH (nadir epiglottic pressure before arousal)...
December 1, 2014: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/25191791/enhanced-upper-airway-muscle-responsiveness-is-a-distinct-feature-of-overweight-obese-individuals-without-sleep-apnea
#11
Scott A Sands, Danny J Eckert, Amy S Jordan, Bradley A Edwards, Robert L Owens, James P Butler, Richard J Schwab, Stephen H Loring, Atul Malhotra, David P White, Andrew Wellman
RATIONALE: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m(2)) for reasons that are not fully elucidated. OBJECTIVES: To determine the key physiologic traits (upper-airway anatomy/collapsibility, upper-airway muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals...
October 15, 2014: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/25085887/effects-of-hyperoxia-and-hypoxia-on-the-physiological-traits-responsible-for-obstructive-sleep-apnoea
#12
Bradley A Edwards, Scott A Sands, Robert L Owens, David P White, Pedro R Genta, James P Butler, Atul Malhotra, Andrew Wellman
Oxygen therapy is known to reduce loop gain (LG) in patients with obstructive sleep apnoea (OSA), yet its effects on the other traits responsible for OSA remain unknown. Therefore, we assessed how hyperoxia and hypoxia alter four physiological traits in OSA patients. Eleven OSA subjects underwent a night of polysomnography during which the physiological traits were measured using multiple 3-min 'drops' from therapeutic continuous positive airway pressure (CPAP) levels. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation...
October 15, 2014: Journal of Physiology
https://www.readbyqxmd.com/read/25061251/obstructive-sleep-apnea-in-older-adults-is-a-distinctly-different-physiological-phenotype
#13
Bradley A Edwards, Andrew Wellman, Scott A Sands, Robert L Owens, Danny J Eckert, David P White, Atul Malhotra
STUDY OBJECTIVES: Current evidence suggests that the pathological mechanisms underlying obstructive sleep apnea (OSA) are altered with age. However, previous studies examining individual physiological traits known to contribute to OSA pathogenesis have been assessed in isolation, primarily in healthy individuals. DESIGN: We assessed the four physiological traits responsible for OSA in a group of young and old patients with OSA. SETTING: Sleep research laboratory...
July 2014: Sleep
https://www.readbyqxmd.com/read/25020212/influence-of-pharyngeal-muscle-activity-on-inspiratory-negative-effort-dependence-in-the-human-upper-airway
#14
Pedro R Genta, Robert L Owens, Bradley A Edwards, Scott A Sands, Danny J Eckert, James P Butler, Stephen H Loring, Atul Malhotra, Andrew C Jackson, David P White, Andrew Wellman
The upper airway is often modeled as a Starling resistor, which predicts that flow is independent of inspiratory effort during flow limitation. However, while some obstructive sleep apnea (OSA) patients exhibit flat, Starling resistor-like flow limitation, others demonstrate considerable negative effort dependence (NED), defined as the percent reduction in flow from peak to mid-inspiration. We hypothesized that the variability in NED could be due to differences in phasic pharyngeal muscle activation between individuals...
September 15, 2014: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/24458746/the-classical-starling-resistor-model-often-does-not-predict-inspiratory-airflow-patterns-in-the-human-upper-airway
#15
Robert L Owens, Bradley A Edwards, Scott A Sands, James P Butler, Danny J Eckert, David P White, Atul Malhotra, Andrew Wellman
The upper airway is often modeled as a classical Starling resistor, featuring a constant inspiratory airflow, or plateau, over a range of downstream pressures. However, airflow tracings from clinical sleep studies often show an initial peak before the plateau. To conform to the Starling model, the initial peak must be of small magnitude or dismissed as a transient. We developed a method to simulate fast or slow inspirations through the human upper airway, to test the hypothesis that this initial peak is a transient...
April 15, 2014: Journal of Applied Physiology
https://www.readbyqxmd.com/read/23889723/the-association-between-obstructive-sleep-apnea-and-hypertension-by-race-ethnicity-in-a-nationally-representative-sample
#16
Megan Sands-Lincoln, Michael Grandner, Julia Whinnery, Brendan T Keenan, Nick Jackson, Indira Gurubhagavatula
The association between obstructive sleep apnea (OSA) and hypertension by race/ethnicity has not been well characterized in a national sample. Adult participants in the 2007-2008 National Health and Nutrition Examination Survey were reviewed by self-report of sleep apnea diagnosis, snorting, gasping or stopping breathing during sleep, and snoring to derive whether OSA was probable (pOSA). Multivariable logistic regression determined whether pOSA predicted hypertension in the overall cohort, and by body mass index (BMI) group and ethno-racial strata...
August 2013: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/23633760/extreme-sleep-durations-and-increased-c-reactive-protein-effects-of-sex-and-ethnoracial-group
#17
Michael A Grandner, Orfeu M Buxton, Nicholas Jackson, Megan Sands-Lincoln, Abhishek Pandey, Girardin Jean-Louis
STUDY OBJECTIVES: We hypothesize that extremes of sleep duration are associated with elevated C-reactive protein (CRP), a pro-inflammatory marker for cardiovascular disease risk. DESIGN: Cross-sectional. SETTING: Population-based research. PARTICIPANTS: Nationally representative sample of 2007-2008 National Health and Nutrition Examination Survey participants (n = 5,587 adults). INTERVENTIONS: None...
May 2013: Sleep
https://www.readbyqxmd.com/read/23372276/acetazolamide-attenuates-the-ventilatory-response-to-arousal-in-patients-with-obstructive-sleep-apnea
#18
RANDOMIZED CONTROLLED TRIAL
Bradley A Edwards, James G Connolly, Lisa M Campana, Scott A Sands, John A Trinder, David P White, Andrew Wellman, Atul Malhotra
STUDY OBJECTIVES: The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorder's severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients. DESIGN: We assessed the ventilatory response to arousal in OSA patients on therapeutic CPAP before and after administration of acetazolamide for 7 days...
February 2013: Sleep
https://www.readbyqxmd.com/read/23349453/a-simplified-method-for-determining-phenotypic-traits-in-patients-with-obstructive-sleep-apnea
#19
Andrew Wellman, Bradley A Edwards, Scott A Sands, Robert L Owens, Shamim Nemati, James Butler, Chris L Passaglia, Andrew C Jackson, Atul Malhotra, David P White
We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH(2)O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive...
April 2013: Journal of Applied Physiology
https://www.readbyqxmd.com/read/22935396/short-sleep-duration-is-associated-with-carotid-intima-media-thickness-among-men-in-the-coronary-artery-risk-development-in-young-adults-cardia-study
#20
Megan R Sands, Diane S Lauderdale, Kiang Liu, Kristen L Knutson, Karen A Matthews, Charles B Eaton, Crystal D Linkletter, Eric B Loucks
BACKGROUND AND PURPOSE: Carotid intima-media thickness (CIMT) is a subclinical marker of cardiovascular disease. Recent studies suggest that shorter sleep duration is a risk factor for cardiovascular disease, but there is limited evidence regarding this association using high-quality, objective assessments of sleep. The aim of this study is to determine whether sleep duration is associated with CIMT. METHODS: The study used an observational cohort consisting of 617 black and white middle-aged healthy participants (37-52 years; 58% female) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study...
November 2012: Stroke; a Journal of Cerebral Circulation
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