ORCID Profile
0000-0003-3503-2363
Current Organisations
University of New South Wales
,
Neuroscience Research Australia
,
Flinders University
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2023
DOI: 10.1161/HYPERTENSIONAHA.122.20513
Abstract: Irregularities in sleep duration and sleep timing have emerged as potential risk factors for hypertension. This study examined associations between irregularity in sleep duration and timing with hypertension in a large, global s le over multiple months. Data from 12 287 adults, who used an under-mattress device to monitor sleep duration and timing and also provided blood pressure recordings on ≥5 separate occasions, were analyzed. Sleep duration irregularity was assessed as the SD in total sleep time across the ≈9-month recording period. Sleep timing irregularity was assessed as SDs in sleep onset time, sleep midpoint, and sleep offset time. Logistic regressions were conducted to investigate associations between sleep irregularity and hypertension, defined as median systolic blood pressure ≥140 mm Hg or median diastolic blood pressure ≥90 mm Hg. Participants were middle-aged (mean±SD, 50±12 years), mostly men (88%) and overweight (body mass index, 28±6 kg/m −2 ). Sleep duration irregularity was consistently associated with an ≈9% to 17% increase in hypertension independently of the total sleep time. A ≈34-minute increase in sleep onset time irregularity was associated with a 32% increase in hypertension (1.32 [1.20–1.45]). A 32-minute increase in sleep midpoint irregularity was associated with an 18% increase in hypertension (1.18 [1.09–1.29]), while a 43-minute increase in sleep offset time irregularity was associated with an 8.9% increase in hypertension (1.09 [1.001–1.18]). These findings support that sleep irregularity, both in duration and timing, is a risk marker for poor cardiovascular health. Further mechanistic investigations of temporal relationships between day-to-day fluctuations in sleep duration and timing, next-day blood pressure, and other cardiovascular outcomes are warranted.
Publisher: American Thoracic Society
Date: 03-2006
Publisher: Oxford University Press (OUP)
Date: 04-03-2022
Abstract: To determine if a novel EEG-derived continuous index of sleep depth/alertness, the odds ratio product (ORP), predicts self-reported daytime sleepiness and poor sleep quality in two large population-based cohorts. ORP values which range from 0 (deep sleep) to 2.5 (fully alert) were calculated in 3s intervals during awake periods (ORPwake) and NREM sleep (ORPNREM) determined from home sleep studies in the HypnoLaus (N = 2162: 1106 females, 1056 males) and men androgen inflammation lifestyle environment and stress (MAILES) cohorts (N = 754 males). Logistic regression was used to examine associations between ORPwake, ORPNREM, and traditional polysomnography measures (as comparators) with excessive sleepiness (Epworth sleepiness scale & ) and poor sleep quality (Pittsburgh sleep quality index & ) and insomnia symptoms. High ORPwake was associated with a ~30% increase in poor sleep quality in both HypnoLaus (odds ratio, OR, and 95% CI) 1.28 (1.09, 1.51), and MAILES 1.36 (1.10, 1.68). High ORPwake was also associated with a ~28% decrease in excessive daytime sleepiness in the MAILES dataset. ORPNREM was associated with a ~30% increase in poor sleep quality in HypnoLaus but not in MAILES. No consistent associations across cohorts were detected using traditional polysomnography markers. ORP, a novel EEG-derived metric, measured during wake periods predicts poor sleep quality in two independent cohorts. Consistent with insomnia symptomatology of poor perceived sleep in the absence of excessive daytime sleepiness, ORPwake may provide valuable objective mechanistic insight into physiological hyperarousal.
Publisher: Public Library of Science (PLoS)
Date: 13-06-2017
Publisher: American Physiological Society
Date: 05-2021
DOI: 10.1152/JAPPLPHYSIOL.01074.2020
Abstract: In contrast to recent findings of major reductions in OSA severity when atomoxetine is combined with a nonspecific antimuscarinic, oxybutynin (broad M-subtype receptor selectivity), addition of solifenacin succinate (M2 and M3 muscarinic receptor selectivity) or biperiden (M1 muscarinic receptor selectivity) with atomoxetine had modest effects on upper airway function during sleep, which provide mechanistic insight into the role of noradrenergic and antimuscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.
Publisher: MDPI AG
Date: 03-07-2023
DOI: 10.3390/BIOS13070703
Abstract: Effective monitoring of respiratory disturbances during sleep requires a sensor capable of accurately capturing chest movements or airflow displacement. Gold-standard monitoring of sleep and breathing through polysomnography achieves this task through dedicated chest/abdomen bands, thermistors, and nasal flow sensors, and more detailed physiology, evaluations via a nasal mask, pneumotachograph, and airway pressure sensors. However, these measurement approaches can be invasive and time-consuming to perform and analyze. This work compares the performance of a non-invasive wearable stretchable morphic sensor, which does not require direct skin contact, embedded in a t-shirt worn by 32 volunteer participants (26 males, 6 females) with sleep-disordered breathing who performed a detailed, overnight in-laboratory sleep study. Direct comparison of computed respiratory parameters from morphic sensors versus traditional polysomnography had approximately 95% (95 ± 0.7) accuracy. These findings confirm that novel wearable morphic sensors provide a viable alternative to non-invasively and simultaneously capture respiratory rate and chest and abdominal motions.
Publisher: Wiley
Date: 12-11-2015
DOI: 10.1111/RESP.12681
Abstract: The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality.
Publisher: American Thoracic Society
Date: 02-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-07-2022
Abstract: Poor sleep quality is associated with increased incident hypertension. However, few studies have investigated the impact of objective sleep structure parameters on hypertension. This study investigated the association between sleep macrostructural and microstructural parameters and incident hypertension in a middle‐ to older‐aged s le. Participants from the HypnoLaus population‐based cohort without hypertension at baseline were included. Participants had at‐home polysomnography at baseline, allowing assessment of sleep macrostructure (nonrapid eye movement sleep stages 1, 2, and 3 rapid eye movement sleep stages and total sleep time) and microstructure including power spectral density of electroencephalogram in nonrapid eye movement sleep and spindles characteristics (density, duration, frequency, litude) in nonrapid eye movement sleep stage 2. Associations between sleep macrostructure and microstructure parameters at baseline and incident clinical hypertension over a mean follow‐up of 5.2 years were assessed with multiple‐adjusted logistic regression. A total of 1172 participants (42% men age 55±10 years) were included. Of these, 198 (17%) developed hypertension. After adjustment for confounders, no sleep macrostructure features were associated with incident hypertension. However, low absolute delta and sigma power were significantly associated with incident hypertension where participants in the lowest quartile of delta and sigma had a 1.69‐fold (95% CI, 1.00–2.89) and 1.72‐fold (95% CI, 1.05–2.82) increased risk of incident hypertension, respectively, versus those in the highest quartile. Lower spindle density (odds ratio, 0.87 95% CI, 0.76–0.99) and litude (odds ratio, 0.98 95% CI, 0.95–1.00) were also associated with higher incident hypertension. Sleep microstructure is associated with incident hypertension. Slow‐wave activity and sleep spindles, 2 hallmarks of objective sleep continuity and quality, were inversely and consistently associated with incident hypertension. This supports the protective role of sleep continuity in the development of hypertension.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.SMRV.2022.101589
Abstract: Impaired upper airway sensation may contribute to obstructive sleep apnea (OSA) pathophysiology and could represent a therapeutic target. However, the extent of impaired sensation and its functional role in OSA pathogenesis remains unclear. This study aimed to: 1) evaluate methods of upper airway sensory testing in people with OSA, 2) compare upper airway sensation in people with and without OSA and 3) investigate the potential relationship between upper airway sensation and OSA severity. Major electronic databases were searched for studies that reported methods of upper airway sensory testing in people with OSA (n = 3819). From the selected studies (n = 38), information on the type of sensation, testing methods, validity and test-retest reliability were extracted. Meta-analyses were performed on case-controlled studies and studies that investigated potential relationships between upper airway sensation and OSA severity. Seven categories of sensory tests were reported: olfactory, gustatory, chemical, tactile, vibratory, thermal and perioral neuro-sensation. Testing methods varied widely across studies. No tests were validated in OSA. People with OSA had impaired upper airway sensation to airflow (p = 0.0002), chemical (p = 0.0001), gustatory (p = 0.009), olfactory (p = 0.04), tactile (p = 0.0001) and vibratory (p = 0.005) stimuli. Upper airway sensory impairment increased with OSA severity (p < 0.001). These findings suggest that, while variable across testing methods, people with OSA have impaired upper airway sensation, which is related to increased OSA severity. Development of valid and reliable upper airway sensory testing methods that relate to upper airway function in people with OSA are required to inform future clinical and research practices and identify potential therapeutic targets.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.RESP.2013.05.007
Abstract: Understanding the inter-relationship between pharmacological agents, ventilatory control, upper airway physiology and their consequent effects on sleep-disordered breathing may provide new directions for targeted drug therapy. Where available, this review focuses on human studies that contain both drug effects on sleep-disordered breathing and measures of ventilatory control or upper airway physiology. Many of the existing studies are limited in s le size or comprehensive methodology. At times, the presence of paradoxical findings highlights the complexity of drug therapy for OSA. The existing studies also highlight the importance of considering inter-in idual pharmacokinetics and underlying causes of sleep apnea in interpreting drug effects on sleep-disordered breathing. Practical ways to assess an in idual's ventilatory control and how it interacts with upper airway physiology is required for future targeted pharmacotherapy in sleep apnea.
Publisher: Wiley
Date: 15-02-2022
DOI: 10.1111/JSR.13563
Abstract: Insomnia and obstructive sleep apnea commonly co‐occur (co‐morbid insomnia and sleep apnea), and their co‐occurrence has been associated with worse cardiometabolic and mental health. However, it remains unknown if people with co‐morbid insomnia and sleep apnea are at a heightened risk of incident cardiovascular events. This study used longitudinal data from the Sleep Heart Health Study ( N = 5803) to investigate potential associations between co‐morbid insomnia and sleep apnea and cardiovascular disease prevalence at baseline and cardiovascular event incidence over ~11 years follow‐up. Insomnia was defined as self‐reported difficulties initiating and/or maintaining sleep AND daytime impairment. Obstructive sleep apnea was defined as an apnea–hypopnea index ≥ 15 events per hr sleep. Co‐morbid insomnia and sleep apnea was defined if both conditions were present. Data from 4160 participants were used for this analysis. The prevalence of no insomnia/obstructive sleep apnea, insomnia only, obstructive sleep apnea only and co‐morbid insomnia and sleep apnea was 53.2%, 3.1%, 39.9% and 1.9%, respectively. Co‐morbid insomnia and sleep apnea was associated with a 75% (odd ratios [95% confidence interval] 1.75 [1.14, 2.67]) increase in likelihood of having cardiovascular disease at baseline after adjusting for pre‐specified confounders. In the unadjusted model, co‐morbid insomnia and sleep apnea was associated with a twofold increase (hazard ratio, 95% confidence interval: 2.00 [1.33, 2.99]) in risk of cardiovascular event incidence. However, after adjusting for pre‐specified covariates, co‐morbid insomnia and sleep apnea was not significantly associated with incident cardiovascular events (hazard ratio 1.38 [0.92, 2.07]). Comparable findings were obtained when an alternative definition of insomnia (difficulties initiating and/or maintaining sleep without daytime impairment) was used.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2019
DOI: 10.1007/S00106-019-0720-9
Abstract: The prevalence of obstructive sleep apnea (OSA) is considered to be very high in western industrialized countries. There are conservative and surgical forms of treatment for OSA however, the pathophysiology is largely unexplained and cannot be explained by anatomical abnormalities alone. In recent years, a number of non-anatomical factors have been found that favor the development of OSA. These include the respiratory excitation threshold (arousals), the respiratory drive (loop gain), as well as the control and function of the muscular upper airway dilators. The understanding of the in idual pathophysiological processes may be helpful in the future to develop in idual treatment approaches for patients.
Publisher: Oxford University Press (OUP)
Date: 10-12-2017
DOI: 10.1093/SLEEP/ZSW047
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JPEDS.2017.07.012
Abstract: To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk. We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals. At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39 breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57 formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections. Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.
Publisher: Wiley
Date: 11-2018
Publisher: American Physiological Society
Date: 02-2014
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-03-2020
DOI: 10.5664/JCSM.8268
Publisher: European Respiratory Society (ERS)
Date: 10-2019
DOI: 10.1183/23120541.00153-2019
Abstract: Endogenous opioids (endorphins) have been reported to modulate exercise-induced breathlessness, but the relative contribution of peripheral opioid receptors has not been tested. This was a double-blind, randomised, three-arm, cross-over trial in outpatients with spirometry-verified moderate to severe chronic obstructive pulmonary disease. Participants undertook an incremental symptom-limited treadmill test followed by five endurance treadmill tests at 75% of their maximal work rate two tests for familiarisation and three tests 30 min after intravenous injection of either methylnaltrexone 0.3 mg·kg −1 (blocking peripheral opioid receptors only) or naloxone 0.1 mg·kg −1 (blocking both central and peripheral opioid receptors) or normal saline, in randomised order. The primary end-point was the regression slope between breathlessness intensity (0–10 numerical rating scale) and oxygen consumption ( V ′ O 2 ) during the walk tests, comparing methylnaltrexone and placebo using a paired t-test. 17 participants completed the trial: median (range) 66 (55–82) years 15 males mean± sd forced expiratory volume (FEV 1 ) 53.8±17.6% predicted FEV 1 /forced vital capacity ratio 0.55±15.9. There was no statistically or clinically significant difference in the primary end-point (regression slope of breathlessness intensity and V ′ O 2 ) for methylnaltrexone (p=0.498) or naloxone (p=0.804), compared to placebo. Secondary outcomes were similar between the three treatment groups, including peak and mean breathlessness intensity and unpleasantness, exercise capacity, endurance time and leg fatigue. Blocking peripheral opioid receptors (methylnaltrexone) or peripheral and central opioid receptors (naloxone) did not appear to modulate breathlessness intensity nor exercise capacity when compared with placebo (no blockade).
Publisher: BMJ
Date: 08-2021
DOI: 10.1136/BMJOPEN-2020-046425
Abstract: This study aimed to explore the relationship (presence and severity) between chronic breathlessness and sleep problems, independently of diagnoses and health service contact by surveying a large, representative s le of the general population. Analysis of the 2017 South Australian Health Omnibus Survey, an annual, cross-sectional, face-to-face, multistage, clustered area systematic s ling survey carried out in Spring 2017. Chronic breathlessness was self-reported using the ordinal modified Medical Research Council (mMRC scores 0 (none) to 4 (housebound)) where breathlessness has been present for more than 3 of the previous 6 months. ‘Sleep problems—ever’ and ‘sleep problem—current’ were assessed dichotomously. Regression models were adjusted for age sex and body mass index (BMI). 2900 responses were available (mean age 48.2 years (SD=18.6) 51% were female mean BMI 27. 1 (SD=5.9)). Prevalence was: 2.7% (n=78) sleep problems—past 6.8% (n=198) sleep problems—current and breathlessness (mMRC 1–4) was 8.8% (n=254). Respondents with sleep problemspast were more likely to be breathless, older with a higher BMI and sleep problems—present also included a higher likelihood of being female. After adjusting for age, sex and BMI, respondents with chronic breathlessness had 1.9 (95% CI=1.0 to 3.5) times the odds of sleep problems—past and sleep problems—current (adjusted OR=2.3 95% CI=1.6 to 3.3). There is a strong association between the two prevalent conditions. Future work will seek to understand if there is a causal relationship using validated sleep assessment tools and whether better managing one condition improves the other.
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/JSR.58_12765
Publisher: American Thoracic Society
Date: 15-02-2008
Publisher: American Physiological Society
Date: 02-2022
DOI: 10.1152/JAPPLPHYSIOL.00478.2021
Abstract: During swallowing, we observed two distinct, stereotyped muscle activation patterns that define the horizontal (monophasic, maximal EMG) and oblique (biphasic, submaximal EMG) neuromuscular compartments of genioglossus. In contrast, volitional tongue protrusions produced uniform activation across compartments. This provides evidence for task-dependent, functionally discrete neuromuscular control of the oblique and horizontal compartments of genioglossus. The magnitude and temporal patterning of genioglossus EMG during swallowing may help guide electrode placement in tongue EMG studies.
Publisher: Frontiers Media SA
Date: 15-01-2018
Publisher: American Physiological Society
Date: 03-2007
DOI: 10.1152/AJPREGU.00642.2006
Abstract: Our aim was to evaluate cardiac changes evoked by spontaneous and sound-induced arousals from sleep. Cardiac responses to spontaneous and auditory-induced arousals were recorded during overnight sleep studies in 28 young healthy subjects (14 males, 14 females) during non-rapid eye movement sleep. Computerized analysis was applied to assess beat-to-beat changes in heart rate, atrio-ventricular conductance, and ventricular repolarization from 30 s before to 60 s after the auditory tone. During both types of arousals, the most consistent change was the increase in the heart rate (in 62% of spontaneous and in 89% of sound-induced arousals). This was accompanied by an increase or no change in PR interval and by a decrease or no change in QT interval. The magnitude of all cardiac changes was significantly higher for tone-induced vs. spontaneous arousals (mean ± SD for heart rate: +9 ± 8 vs. +13 ± 9 beats per min for PR prolongation: 14 ± 16 vs. 24 ± 22 ms for QT shortening: −12 ± 6 vs. −20 ± 9 ms). The prevalence of transient tachycardia and PR prolongation was also significantly higher for tone-induced vs. spontaneous arousals (tachycardia: 85% vs. 57% of arousals, P 0.001 PR prolongation: 51% vs. 25% of arousals, P 0.001). All cardiac responses were short-lasting (10–15 s). We conclude that cardiac pacemaker region, conducting system, and ventricular myocardium may be under independent neural control. Prolongation of atrio-ventricular delay may serve to increase ventricular filling during arousal from sleep. Whether prolonged atrio-ventricular conductance associated with increased sympathetic outflow to the ventricular myocardium contributes to arrhythmogenesis during sudden arousal from sleep remains to be evaluated.
Publisher: American Physiological Society
Date: 12-2010
DOI: 10.1152/JAPPLPHYSIOL.00812.2010
Abstract: Single motor unit (SMU) analysis provides a means to examine the motor control of a muscle. SMUs in the genioglossus show considerable complexity, with several different firing patterns. Two of the primary stimuli that contribute to genioglossal activation are carbon dioxide (CO 2 ) and negative pressure, which act through chemoreceptor and mechanoreceptor activation, respectively. We sought to determine how these stimuli affect the behavior of genioglossus SMUs. We quantified genioglossus SMU discharge activity during periods of quiet breathing, elevated CO 2 (facilitation), and continuous positive airway pressure (CPAP) administration (inhibition). CPAP was applied in 2-cmH 2 O increments until 10 cmH 2 O during hypercapnia. Five hundred ninety-one periods (each ∼3 breaths) of genioglossus SMU data were recorded using wire electrodes( n = 96 units) from 15 awake, supine subjects. Overall hypercapnic stimulation increased the discharge rate of genioglossus units (20.9 ± 1.0 vs. 22.7 ± 0.9 Hz). Inspiratory units were activated ∼13% earlier in the inspiratory cycle, and the units fired for a longer duration (80.6 ± 5.1 vs. 105.3 ± 4.2% inspiratory time P 0.05). Compared with baseline, an additional 32% of distinguishable SMUs within the selective electrode recording area were recruited with hypercapnia. CPAP led to progressive SMU inhibition at ∼6 cmH 2 O, there were similar numbers of SMUs active compared with baseline, with peak frequencies of inspiratory units close to baseline, despite elevated CO 2 levels. At 10 cmH 2 O, the number of units was 36% less than baseline. Genioglossus inspiratory phasic SMUs respond to hypercapnic stimulation with changes in recruitment and rate coding. The SMUs respond to CPAP with derecruitment as a homogeneous population, and inspiratory phasic units show slower discharge rates. Understanding upper airway muscle recruitment/derecruitment may yield therapeutic targets for maintenance of pharyngeal patency.
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Physiological Society
Date: 09-2012
DOI: 10.1152/JAPPLPHYSIOL.00091.2012
Abstract: The passive pharyngeal critical closing pressure (Pcrit) is measured using a series of pressure drops. However, pressure drops also lower end-expiratory lung volume (EELV), which independently affects Pcrit. We describe a technique to measure Pcrit at a constant EELV. Continuous positive airway pressure (CPAP)-treated obstructive sleep apnea (OSA) patients and controls were instrumented with an epiglottic catheter, magnetometers (to measure change in EELV), and nasal mask neumotachograph and slept supine on nasal CPAP. Pcrit was measured in standard fashion and using our novel “biphasic technique” in which expiratory pressure only was lowered for 1 min before the inspiratory pressure was dropped this allowed EELV to decrease to the drop level before performing the pressure drop. Seven OSA and three controls were studied. The biphasic technique successfully lowered EELV before the inspiratory pressure drop. Pcrit was similar between the standard and biphasic techniques (−0.4 ± 2.6 vs. −0.6 ± 2.3 cmH 2 O, respectively, P = 0.84). Interestingly, we noted three different patterns of flow limitation: 1) classic Starling resistor type: flow fixed and independent of downstream pressure 2) negative effort dependence within breaths: substantial decrease in flow, sometimes with complete collapse, as downstream pressure decreased and 3) and negative effort dependence across breaths: progressive reductions in peak flow as respiratory effort on successive breaths increased. Overall, EELV changes do not influence standard passive Pcrit measurements if breaths 3–5 of pressure drops are used. These results also highlight the importance of inspiratory collapse in OSA pathogenesis. The cause of negative effort dependence within and across breaths is not known and requires further study.
Publisher: Elsevier BV
Date: 02-2007
Publisher: Oxford University Press (OUP)
Date: 12-01-2021
Abstract: Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2) %total sleep time, p & 0.001) with a small increase in apnea–hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3) p & 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p & 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.
Publisher: European Respiratory Society (ERS)
Date: 05-12-2016
DOI: 10.1183/13993003.00959-2016
Abstract: The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a “marker” of disease severity or a “mediator” of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation.
Publisher: European Respiratory Society (ERS)
Date: 25-11-2022
DOI: 10.1183/13993003.01788-2021
Abstract: Recent advances in obstructive sleep apnoea (OSA) pathophysiology and translational research have opened new lines of investigation for OSA treatment and management. Key goals of such investigations are to provide efficacious, alternative treatment and management pathways that are better tailored to in idual risk profiles to move beyond the traditional continuous positive airway pressure (CPAP)-focused, “one size fits all” trial-and-error approach, which is too frequently inadequate for many patients. Identification of different clinical manifestations of OSA (clinical phenotypes) and underlying pathophysiological phenotypes (endotypes) that contribute to OSA have provided novel insights into underlying mechanisms and have underpinned these efforts. Indeed, this new knowledge has provided the framework for precision medicine for OSA to improve treatment success rates with existing non-CPAP therapies such as mandibular advancement devices and upper airway surgery, and newly developed therapies such as hypoglossal nerve stimulation and emerging therapies such as pharmacotherapies and combination therapy. Additionally, these concepts have provided insight into potential physiological barriers to CPAP adherence for certain patients. This review summarises the recent advances in OSA pathogenesis, non-CPAP treatment, clinical management approaches and highlights knowledge gaps for future research. OSA endotyping and clinical phenotyping, risk stratification and personalised treatment allocation approaches are rapidly evolving and will further benefit from the support of recent advances in e-health and artificial intelligence.
Publisher: Oxford University Press (OUP)
Date: 10-2014
DOI: 10.5665/SLEEP.4078
Publisher: Oxford University Press (OUP)
Date: 06-2015
DOI: 10.5665/SLEEP.4750
Publisher: Elsevier BV
Date: 09-2014
Publisher: Informa UK Limited
Date: 10-2022
DOI: 10.2147/NSS.S379252
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.SMRV.2019.101229
Abstract: Mandibular advancement device (MAD) therapy is the most commonly used non-continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA). Although OSA patients prefer MAD over CPAP, on average over one third have minimal or no major reduction in OSA severity with MAD therapy. Improved understanding of responder characteristics (or "phenotypes") to MAD may facilitate more efficient use of limited medical resources and optimize treatment efficacy. The aim of this review is to describe the baseline phenotypic characteristics of responders to MAD therapy in OSA patients. Pubmed, Web of Science, EMBASE, Scopus were searched for eligible studies published until Feb 2019. A total of 650 studies were identified. 41 studies were included in this review and meta-analysis. The quality of the studies was assessed using the risk of bias assessment tool for non-randomized studies (RoBANS). Based on meta-analysis, the responders to MAD therapy had certain clinical phenotypic characteristics: lower age (95% CI: -4.55 to -1.62, p < 0.00001), female (95% CI: 0.56 to 0.91, p = 0.006), lower body mass index (95% CI: -2.80 to -1.11, p < 0.00001), smaller neck circumference (95% CI: -1.57 to -0.52, p < 0.00001), lower apnea-hypopnea index (95% CI: -7.23 to -1.89, p < 0.00001), a retracted maxilla and mandible, a narrower airway and a shorter soft palate than non-responders. The above-mentioned phenotypic responder characteristics provides useful information for the clinician when considering prescribing MAD therapy for OSA patients.
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Thoracic Society
Date: 07-2022
Publisher: American Thoracic Society
Date: 05-2011
Publisher: American Physiological Society
Date: 11-2020
DOI: 10.1152/JAPPLPHYSIOL.00393.2020
Abstract: Combined CPAP and oral appliance therapy has been suggested as an alternative for incomplete responders to oral appliance therapy. We used a novel oral appliance incorporating an oral airway together with CPAP to show that pharyngeal pressure swings were normalized at reduced CPAP levels. Our findings demonstrate that using CPAP and oral appliance together may be a beneficial alternative for incomplete responders to oral appliance therapy and intolerant CPAP users due to high-pressure requirements.
Publisher: Oxford University Press (OUP)
Date: 21-02-2019
DOI: 10.1093/SLEEP/ZSZ049
Abstract: Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy. Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome. Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement. Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy.
Publisher: Wiley
Date: 30-08-2020
DOI: 10.1113/JP280173
Publisher: Wiley
Date: 25-08-2004
DOI: 10.1113/JPHYSIOL.2004.066084
Abstract: Sleep hypoventilation is common in hypercapnic chronic obstructive pulmonary disease (COPD) and may contribute to daytime hypercapnia. The contributions of respiratory drive and respiratory mechanics to alterations in minute ventilation ( V̇ I ) during sleep in this group have not been assessed. We assessed V̇ I , breathing pattern, upper airway and total lung resistance (UAR, R L ), intraoesohageal diaphragmatic EMG (EMG oes ), intrinsic positive end‐expiratory pressure (PEEP i ), dynamic compliance ( C dyn ), pressure–time product of oesophageal pressure (PTP oes ), tension–time index of the diaphragm (TTI di ), end‐expiratory lung volume (EELV) and respiratory drive (assessed as the slope of P oes versus time in the isovolumetric interval before PEEP i is overcome). Measurements were made in wakefulness and non‐rapid eye movement (NREM) sleep, on 76%N 2 /24%O 2 and on 76%He/24%O 2 (heliox). Satisfactory data for analysis were obtained in 10 patients five had measurements on heliox. V̇ I fell from (mean ( s.e.m. )) 8.84(0.46) to 6.64(0.91 l min −1 , P = 0.011) between wakefulness and stage II sleep, due to a fall in tidal volume. No changes were seen in PEEP i , C dyn , EELV, PTP oes , TTI di , EMG oes or respiratory drive. UAR increased (3.11(0.8) to 10.24(2.96) cmH 2 O l −1 s ( P = 0.013) but R L was unchanged. UAR was reduced on heliox (5.20(1.67) to 3.45(1.35) cmH 2 O l −1 s, P = 0.049) but V̇ I during sleep did not increase. PTP oes (350.2(51.0) to 259.4(46.3) cmH 2 O s min −1 , P = 0.016), TTI di (0.13(0.02) to 0.10(0.02) P = 0.04), and respiratory drive (20.48(4.69) to 15.02(4.57) cmH 2 O s −1 , P = 0.01) were all reduced. This suggests respiratory drive alters to maintain a preset V̇ I in sleep, irrespective of load, at least while the fatigue threshold of respiratory muscles is not exceeded.
Publisher: American Thoracic Society
Date: 15-10-2014
Publisher: European Respiratory Society (ERS)
Date: 16-09-2021
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JPAINSYMMAN.2018.07.010
Abstract: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness "right now"-morning and evening-measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness "right now" was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm effect size (80% CI) = -0.22 (-0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm effect size (80% CI) = -0.33 (-0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target s le size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.
Publisher: American Thoracic Society
Date: 04-2022
Publisher: American Physiological Society
Date: 08-2018
DOI: 10.1152/JAPPLPHYSIOL.00065.2018
Abstract: Pharyngeal and respiratory sensation is impaired in obstructive sleep apnea (OSA). Opioids may further diminish respiratory sensation. Thus protective pharyngeal neuromuscular and arousal responses to airway occlusion that rely on respiratory sensation could be impaired with opioids to worsen OSA severity. However, little is known about the effects of opioids on upper airway and respiratory sensation in people with OSA. This study was designed to determine the effects of 40 mg of MS-Contin on tactile sensation, respiratory load detection, and respiratory magnitude perception in people with OSA during wakefulness. A double-blind, randomized, crossover design (1 wk washout) was used. Twenty-one men with untreated OSA (apnea/hypopnea index = 26 ± 17 events/h) recruited from a larger clinical study completed the protocol. Tactile sensation using von Frey filaments on the back of the hand, internal mucosa of the cheek, uvula, and posterior pharyngeal wall were not different between placebo and morphine [e.g., median (interquartile range) posterior wall = 0.16 (0.16, 0.4) vs. 0.4 (0.14, 1.8) g, P = 0.261]. Similarly, compared with placebo, morphine did not alter respiratory load detection thresholds for nadir mask pressure detected = −2.05 (−3.37, −1.55) vs. −2.19 (−3.36, −1.41) cmH 2 O, P = 0.767], or respiratory load magnitude perception [mean ± SD Borg scores during a 5 resistive load (range: 5–126 cmH 2 O·l −1 ·s −1 ) protocol = 4.5 ± 1.6 vs. 4.2 ± 1.2, P = 0.347] but did reduce minute ventilation during quiet breathing (11.4 ± 3.3 vs. 10.7 ± 2.6 l/min, P 0.01). These findings indicate that 40 mg of MS-Contin does not systematically impair tactile or respiratory sensation in men with mild to moderate, untreated OSA. This suggests that altered respiratory sensation to acute mechanical stimuli is not likely to be a mechanism that contributes to worsening of OSA with a moderate dose of morphine. NEW & NOTEWORTHY Forty milligrams of MS-Contin does not alter upper airway tactile sensation, respiratory load detection thresholds, or respiratory load magnitude perception in people with obstructive sleep apnea but does decrease breathing compared with placebo during wakefulness. Despite increasing concerns of harm with opioids, the current findings suggest that impaired respiratory sensation to acute mechanical stimuli with this dose of MS-Contin is unlikely to be a direct mechanism contributing to worsening sleep apnea severity in people with mild-to-moderate disease.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.SMRV.2016.12.003
Abstract: People develop obstructive sleep apnoea (OSA) for different reasons. The ability to understand these reasons, easily identify them in in idual patients, and develop therapies that target one or more of these reasons are the keys to unlocking new approaches for the treatment of OSA. In line with this approach, recent advances in OSA pathogenesis using upper airway and respiratory phenotyping techniques have identified four key causes of OSA. A narrow or collapsible upper airway ('impaired anatomy') is the primary cause. However, the anatomical contribution to OSA varies substantially. Indeed, impairment in pharyngeal anatomy can be modest and in many patients (∼20%), pharyngeal collapsibility asleep is not different to people without OSA. Thus, non-anatomical factors or 'phenotypes' that modulate pharyngeal patency are crucial determinants of OSA for many people. These include impairment in pharyngeal dilator muscle control and function during sleep, increased propensity for awakening during airway narrowing (low respiratory arousal threshold) and respiratory control instability (high loop gain). Each phenotype is a potential therapeutic target. This review summarises the recent advances in the understanding of OSA pathogenesis according to a phenotypic approach, emerging tools to identify the phenotypes, and potential new therapeutic pathways and interventions to treat this common disorder.
Publisher: European Respiratory Society (ERS)
Date: 12-03-2020
DOI: 10.1183/13993003.01344-2019
Abstract: Accidental opioid-related deaths are increasing. These often occur during sleep. Opioids such as morphine may worsen obstructive sleep apnoea (OSA). Thus, people with OSA may be at greater risk of harm from morphine. Possible mechanisms include respiratory depression and reductions in drive to the pharyngeal muscles to increase upper airway collapsibility. However, the effects of morphine on the four key phenotypic causes of OSA (upper airway collapsibility (pharyngeal critical closure pressure P crit ), pharyngeal muscle responsiveness, respiratory arousal threshold and ventilatory control (loop gain) during sleep) are unknown. 21 males with OSA (apnoea–hypopnoea index range 7–67 events·h −1 ) were studied on two nights (1-week washout) according to a double-blind, randomised, cross-over design (ACTRN12613000858796). Participants received 40 mg of MS-Contin on one visit and placebo on the other. Brief reductions in continuous positive airway pressure (CPAP) from the therapeutic level were delivered to induce airflow limitation during non-rapid eye movement (REM) sleep to quantify the four phenotypic traits. Carbon dioxide was delivered via nasal mask on therapeutic CPAP to quantify hypercapnic ventilatory responses during non-REM sleep. Compared to placebo, 40 mg of morphine did not change P crit (−0.1±2.4 versus −0.4±2.2 cmH 2 O, p=0.58), genioglossus muscle responsiveness (−2.2 (−0.87 to −5.4) versus −1.2 (−0.3 to −3.5) μV·cmH 2 O −1 , p=0.22) or arousal threshold (−16.7±6.8 versus −15.4±6.0 cmH 2 O, p=0.41), but did reduce loop gain (−10.1±2.6 versus −4.4±2.1, p=0.04) and hypercapnic ventilatory responses (7.3±1.2 versus 6.1±1.5 L·min −1 , p=0.006). Concordant with recent clinical findings, 40 mg of MS-Contin does not systematically impair airway collapsibility, pharyngeal muscle responsiveness or the arousal threshold in moderately severe OSA patients. However, consistent with blunted chemosensitivity, ventilatory control is altered.
Publisher: European Respiratory Society (ERS)
Date: 08-2004
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.5665/SLEEP.6304
Publisher: American Physiological Society
Date: 06-2011
DOI: 10.1152/JAPPLPHYSIOL.00972.2010
Abstract: There is not a clinically available technique for measuring the physiological traits causing obstructive sleep apnea (OSA). Therefore, it is often difficult to determine why an in idual has OSA or to what extent the various traits contribute to the development of OSA. In this study, we present a noninvasive method for measuring four important physiological traits causing OSA: 1) pharyngeal anatomy/collapsibility, 2) ventilatory control system gain (loop gain), 3) the ability of the upper airway to dilate/stiffen in response to an increase in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which continuous positive airway pressure (CPAP) is dropped from an optimum to various suboptimum pressures for 3- to 5-min intervals during sleep. Each in idual's set of traits is entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that in idual. Results from 14 subjects (10 with OSA) are described. Repeatability measurements from separate nights are also presented for four subjects. The measurements and model illustrate the multifactorial nature of OSA pathogenesis and how, in some in iduals, small adjustments of one or another trait (which might be achievable with non-CPAP agents) could potentially treat OSA. This technique could conceivably be used clinically to define a patient's physiology and guide therapy based on the traits.
Publisher: American Thoracic Society
Date: 06-2004
Publisher: American Physiological Society
Date: 11-2011
DOI: 10.1152/JAPPLPHYSIOL.00508.2011
Abstract: The critical closing pressure (Pcrit) is the airway pressure at which the airway collapses and reflects the anatomical contribution to the genesis of obstructive sleep apnea. Pcrit is usually determined during non-rapid eye movement sleep at night, but has been determined under midazolam sedation during the day in the absence of sleep stage monitoring. Indeed, little is known about the effects of midazolam on sleep architecture. Moreover, deeper sedation with midazolam can decrease upper airway muscle activity and increase collapsibility compared with natural sleep. Pcrit under sedation has not been systematically compared with the usual method performed during natural sleep. Therefore, this study aimed to test the hypothesis that Pcrit following low doses of midazolam during the day would be comparable to Pcrit measured during natural sleep in the same patient. Fifteen men (age 54 ± 10 yr, body mass index 30 ± 4 kg/m 2 ) with obstructive sleep apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index 38 ± 22 events/h, range: 8–66 events/h), and Pcrit was determined during natural sleep and following midazolam. Sleep induction was obtained with low doses of midazolam (2.4 mg, range 2.0–4.4 mg), and sleep architecture was comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (−0.82 ± −3.44 and −0.97 ± 3.21 cmH 2 O, P = 0.663) and closely associated (intraclass correlation coefficient = 0.92 95% confidence interval, 0.78–0.97, P 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep apnea severity, indicating that both Pcrit measures provided meaningful physiological information. Pcrit determined during the day with sleep induction is similar to natural overnight sleep and is a valid alternative approach in which to determine Pcrit.
Publisher: European Respiratory Society (ERS)
Date: 12-2017
DOI: 10.1183/13993003.01344-2017
Abstract: Hypnotics are contraindicated in obstructive sleep apnoea (OSA) because of concerns of pharyngeal muscle relaxation and delayed arousal worsening hypoxaemia. However, human data are lacking. This study aimed to determine the effects of three common hypnotics on the respiratory arousal threshold, genioglossus muscle responsiveness and upper airway collapsibility during sleep. 21 in iduals with and without OSA (18–65 years) completed 84 detailed sleep studies after receiving temazepam (10 mg), zolpidem (10 mg), zopiclone (7.5 mg) and placebo on four occasions in a randomised, double-blind, placebo-controlled, crossover trial (ACTRN12612001004853). The arousal threshold increased with zolpidem and zopiclone versus placebo (mean± sd −18.3±10 and −19.1±9 versus −14.6±7 cmH 2 O p=0.02 and p .001) but not with temazepam (−16.8±9 cmH 2 O p=0.17). Genioglossus muscle activity during stable non-REM sleep and responsiveness during airway narrowing was not different with temazepam and zopiclone versus placebo but, paradoxically, zolpidem increased median muscle responsiveness three-fold during airway narrowing (median −0.15 (interquartile range −1.01 to −0.04) versus −0.05 (−0.29 to −0.03)% maximum EMG per cmH 2 O epiglottic pressure p=0.03). The upper airway critical closing pressure did not change with any of the hypnotics. These doses of common hypnotics have differential effects on the respiratory arousal threshold but do not reduce upper airway muscle activity or alter airway collapsibility during sleep. Rather, muscle activity increases during airway narrowing with zolpidem.
Publisher: Wiley
Date: 06-06-2007
Publisher: Oxford University Press (OUP)
Date: 22-08-2018
DOI: 10.1093/SLEEP/ZSY160
Publisher: European Respiratory Society (ERS)
Date: 16-10-2014
DOI: 10.1183/09031936.00062914
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 .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.
Publisher: American Thoracic Society
Date: 04-2023
Publisher: Wiley
Date: 10-04-2019
DOI: 10.1111/JSR.12853
Abstract: New knowledge on hypnotics and their effects on the phenotypic causes of obstructive sleep apnea indicate that zolpidem has therapeutic potential for certain patients. Specifically, zolpidem increases the threshold for arousal threshold and pharyngeal dilator muscle responsiveness. However, the effects of a standard dose of zolpidem (10 mg) on obstructive sleep apnea severity and symptoms have not been investigated. In an open-label pilot study, 12 unselected people with obstructive sleep apnea were recruited following a diagnostic in-laboratory sleep study. Participants then returned for a single-night sleep study in which 10 mg of zolpidem was given just prior to sleep. Tolerability, next-day sleepiness and the effects of zolpidem on polysomnography variables were assessed. Zolpidem was well tolerated and significantly improved the sleep efficiency compared with the no-drug night (77 ± 12% versus 84 ± 9%, p = 0.005). In idual responses on obstructive sleep apnea severity to zolpidem in this unselected obstructive sleep apnea patient population were variable with no overall systematic difference in apnea-hypopnea index (29 ± 18.2 events per hr versus 33 ± 28 events per hr, p = 0.45) or other key respiratory parameters (e.g. event duration or hypoxemia). Next-day sleepiness assessed via the Karolinska Sleepiness Scale was not different between visits (4 ± 1 versus 4 ± 2, p = 0.85). These findings provide the first insight into the effects of a standard dose of zolpidem in obstructive sleep apnea, and highlight its tolerability and potential to improve sleep quality. The variable effects on obstructive sleep apnea severity observed in this pilot also underscore the need for larger trials that incorporate phenotypic characterisation (e.g. arousal threshold, Pcrit and muscle responsiveness) to understand inter-in idual heterogeneity and the therapeutic potential of zolpidem for certain people with obstructive sleep apnea.
Publisher: Wiley
Date: 10-2018
Publisher: Wiley
Date: 10-2018
Publisher: Wiley
Date: 16-01-2020
DOI: 10.1113/JP278769
Publisher: American Thoracic Society
Date: 10-2016
Publisher: American Physiological Society
Date: 09-2022
DOI: 10.1152/JAPPLPHYSIOL.00083.2021
Abstract: Our findings indicate that 30% of participants had regional heterogeneity in reflex morphology (excitation/inhibition) to brief pulses of negative upper-airway pressure across anterior oblique, anterior horizontal, posterior oblique, and posterior horizontal regions of the genioglossus muscle. Reflex excitation litude was proportional to prestimulus drive, with increased activation in oblique compared with horizontal regions of the posterior tongue. People with narrower upper-airway anatomy tended to have increased genioglossus reflex litude to negative pressure pulses during wakefulness.
Publisher: American Physiological Society
Date: 08-2010
DOI: 10.1152/JAPPLPHYSIOL.00373.2010
Abstract: Increasing either genioglossus muscle activity (GG) or end-expiratory lung volume (EELV) improves airway patency but not sufficiently for adequate treatment of obstructive sleep apnea (OSA) in most patients. The mechanisms by which these variables alter airway collapsibility likely differ, with increased GG causing airway dilation, whereas increased EELV may stiffen the airway walls through caudal traction. We sought to determine whether the airway stabilizing effect of GG activation is enhanced when EELV is increased. To investigate this aim, 15 continuous positive airway pressure (CPAP)-treated OSA patients were instrumented with an epiglottic catheter, intramuscular GG-EMG electrodes, magnetometers, and a nasal mask neumotachograph. Subjects slept supine in a sealed, head-out plastic chamber in which the extra-thoracic pressure could be lowered (to raise EELV) while on nasal CPAP with a variable deadspace to allow CO 2 stimulation (and GG activation). The pharyngeal critical closing pressure (P CRIT ) was measured by sudden reduction of CPAP for three to five breaths each minute during non-rapid eye movement (NREM) sleep in 4 conditions: a) baseline, b) 500 ml increased EELV, c) 50% increased GG, and d) conditions b and c combined. P CRIT was found to be reduced from 2.2 ± 0.7 cmH 2 O at baseline to −1.0 ± 0.5 with increased EELV, 0.6 ± 0.7 with increased GG and −1.6 ± 0.7 when both variables were raised ( P 0.001). The slope of the P CRIT curves remained unchanged in all conditions ( P = 0.05). However, the CPAP level at which flow limitation developed was lower in both increased EELV conditions ( P = 0.001). These findings indicate that while both increased GG and EELV improve airway collapsibility, the combination of both variables has little additional effect over increasing EELV alone.
Publisher: American Thoracic Society
Date: 15-10-2022
Publisher: European Respiratory Society (ERS)
Date: 02-12-2021
DOI: 10.1183/13993003.01958-2021
Abstract: Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk. Insomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea–hypopnoea index ≥15 events·h −1 . COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up. 5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39–2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11–2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06–2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia. COMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA.
Publisher: American Physiological Society
Date: 02-2010
DOI: 10.1152/JAPPLPHYSIOL.00755.2009
Abstract: Changes in end-expiratory lung volume (EELV) affect upper airway stability. The passive pharyngeal critical pressure (Pcrit), a measure of upper airway collapsibility, is determined using airway pressure drops. The EELV change during these drops has not been quantified and may differ between obese obstructive sleep apnea (OSA) patients and controls. Continuous positive airway pressure (CPAP)-treated OSA patients and controls were instrumented with an epiglottic catheter, magnetometers (to measure change in EELV), and a nasal mask neumotachograph. Subjects slept supine in a head-out plastic chamber in which the extrathoracic pressure could be lowered (to raise EELV) while on nasal CPAP. The magnitude of EELV change during Pcrit measurement (sudden reductions of CPAP for 3–5 breaths each minute) was assessed at baseline and with EELV increased ∼500 ml. Fifteen OSA patients and 7 controls were studied. EELV change during Pcrit measurement was rapid and pressure dependent, but similar in OSA and control subjects (74 ± 36 and 59 ± 24 ml/cmH 2 O respectively, P = 0.33). Increased lung volume (mean +521 ml) decreased Pcrit by a similar amount in OSA and control subjects (−3.1 ± 1.7 vs. −3.9 ± 1.9 cmH 2 O, P = 0.31). Important lung volume changes occur during passive Pcrit measurement. However, on average, there is no difference in lung volume change for a given CPAP change between obese OSA subjects and controls. Changes in lung volume alter Pcrit substantially. This work supports a role for lung volume in the pathogenesis of OSA, and lung volume changes should be a consideration during assessment of pharyngeal mechanics.
Publisher: Wiley
Date: 13-02-2012
Publisher: Oxford University Press (OUP)
Date: 07-2014
DOI: 10.5665/SLEEP.3844
Publisher: Wiley
Date: 10-2018
Publisher: Oxford University Press (OUP)
Date: 04-2016
DOI: 10.5665/SLEEP.5622
Publisher: Springer Science and Business Media LLC
Date: 14-12-2016
DOI: 10.1007/S11325-016-1442-9
Abstract: The purpose of the present study is to investigate sleep-disordered breathing and symptoms of sleepiness in a consecutive clinical cohort of multiple sclerosis (MS) patients. Twenty-one (16 females) community-dwelling adults aged 18-75 years with MS and an Expanded Disability Status Scale score between 2 and 6 were recruited consecutively from an academic teaching hospital MS clinic. Participants performed a home sleep study (ResMed ApneaLink Plus) to objectively quantify sleep-disordered breathing. Subjective sleepiness and its impact were assessed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Functional Outcomes of Sleep Questionnaire. Three (one female) of the 19 participants who completed home overnight testing had central sleep apnea (median apnea-hypopnea index = 15 [range = 8-36] events/h sleep, median nadir SaO Home sleep testing was well tolerated, and a high proportion of central rather than obstructive sleep apnea was observed in a clinical MS s le. Possible reasons include brainstem or spinal cord lesions from MS affecting the control of breathing. Poor sleep quality and daytime sleepiness were common in this group.
Publisher: Oxford University Press (OUP)
Date: 04-11-2020
Abstract: To investigate whether the presence of tendinous PMR could predict treatment outcome and how it affects lateral wall mechanical properties. Mandibular advancement increases the lateral dimensions of the nasopharyngeal airway via a direct connection from the airway to the ramus of the mandible. The anatomical structure in this region is the pterygomandibular raphe (PMR), but a tendinous component is not always present. Whether tendon presence influences treatment outcome is unknown. In total, 105 participants with obstructive sleep apnea completed detailed anatomical magnetic resonance imaging with and without mandibular advancement. The study design was case–control. Variables were compared between participants with and without the tendon present. The amount of maximum mandibular advancement decreased when pterygomandibular tendon was present (4.0 ± 1.2 mm present versus 4.6 ± 1.4 mm absent, p = 0.04). PMR tendon-absent participants had a lower posttreatment apnea hypopnea index (16 ± 12 events/hour tendon present versus 9 ± 9 events/hour absent, p = 0.007) and were more likely to have complete response (63% versus 36%, p = 0.02). However, tendon-absent participants were more likely to not complete the study (χ 2 (3) = 10.578, p = 0.014). Tendon-absent participants had a greater increase in midline anteroposterior airway diameter (1.6 ± 1.7 mm versus 0.6 ± 2.3 mm, p = 0.04). When PMR tendon is absent, treatment response and amount of maximum advancement improve, possibly at the expense of reduced splint tolerability. Tendon presence may help predict a group less likely to respond to mandibular advancement splint therapy.
Publisher: American Thoracic Society
Date: 15-05-2019
Publisher: Springer Science and Business Media LLC
Date: 29-08-2019
DOI: 10.1007/S11325-019-01930-3
Abstract: Implementation of mandibular advancement splint (MAS) therapy as first-line treatment for obstructive sleep apnoea (OSA) is hindered by inter-in idual variability of treatment outcomes and lack of robust patient selection methods. Optimal continuous positive airway pressure (CPAP) requirement provides an estimate of airway collapsibility severity, and high CPAP requirements predict MAS therapy failure in retrospective studies. Thus, understanding the effects of mandibular advancement on optimal CPAP requirements may enhance optimisation of patient selection for MAS therapy. This study aims to determine dose-dependent effects of mandibular advancement on optimal CPAP requirements in OSA. Prior to MAS therapy initiation, participants with OSA (apnoea-hypopnea index (AHI) > 10 events/h) underwent a research polysomnogram in which a remotely controlled mandibular positioner (RCMP) was used to determine dose-response effects of varying mandibular advancement positions (0% 'habitual bite' and 25, 50, 75 and 100% of maximum mandibular advancement, in random order) on optimal CPAP requirements. A separate polysomnography determined treatment outcome. Data are presented as mean ± SD or median (1st-3rd quartiles). Seventeen participants (age = 47 ± 9 years, body mass index = 26 kg/m Increasing mandibular advancement lowers optimal CPAP requirements in a dose-dependent manner. This supports prior work indicating a beneficial effect of MAS on upper airway collapsibility.
Publisher: Oxford University Press (OUP)
Date: 11-2011
DOI: 10.5665/SLEEP.1380
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 08-04-2020
Abstract: Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility. A total of 35 participants (15 female) with OSA (mean ± SD apnea–hypopnea index = 35 ± 19 events/h) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration, where CPAP was transiently turned off from the therapeutic pressure for ≤5 breaths/efforts on ≥5 occasions during stable non-rapid eye movement (non-REM) sleep for quantitative assessment of airflow responses (%peak inspiratory flow [PIF] from preceding 5 breaths). Participants then underwent an overnight physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess airflow response reproducibility. Mean PIF of breaths 3–5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 ± 29% vs. 28 ± 30% on therapeutic CPAP, p = 0.2 range 0%–90% vs. 0%–95%). Pcrit was −1.0 ± 2.5 cmH2O (range −6 to 5 cmH2O). Mean PIF during zero CPAP on the simple clinical intervention and the physiology night correlated with Pcrit (r = −0.7 and −0.9, respectively, p & 0.0001). Receiver operating characteristic curve analysis indicated significant diagnostic utility for the simple intervention to predict Pcrit & −2 and & 0 cmH2O (AUC = 0.81 and 0.92), respectively. A simple CPAP intervention can successfully discriminate between patients with and without mild to moderately collapsible pharyngeal airways. This scalable approach may help select in iduals most likely to respond to non-CPAP therapies.
Publisher: Wiley
Date: 22-10-2023
DOI: 10.1111/JSR.14069
Publisher: European Respiratory Society
Date: 12-2010
Publisher: Elsevier BV
Date: 04-2009
Publisher: American Thoracic Society
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 13-02-2019
DOI: 10.1038/S41393-019-0256-6
Abstract: Prospective, double-blind, randomised, placebo-controlled, cross-over trial of nasal decongestion in tetraplegia. Tetraplegia is complicated by severe, predominantly obstructive, sleep apnoea. First-line therapy for obstructive sleep apnoea is nasal continuous positive airway pressure, but this is poorly tolerated. High nasal resistance associated with unopposed parasympathetic activation of the upper airway contributes to poor adherence. This preliminary study tested whether reducing nasal decongestion improved sleep. Participants' homes in Melbourne and Sydney, Australia. Two sleep studies were performed in participants' homes separated by 1 week. Participants were given a nasal spray (0.5 mL of 5% phenylephrine or placebo) in random order and posterior nasal resistance measured immediately. Outcomes included sleep apnoea severity, perceived nasal congestion, sleep quality and oxygenation during sleep. Twelve middle-aged (average (SD) 52 (12) years) overweight (body mass index 25.3 (6.7) kg/m These preliminary data found that phenylephrine acutely reduced nasal resistance but did not significantly change sleep-disordered breathing severity.
Publisher: American Thoracic Society
Date: 25-10-2023
Publisher: European Respiratory Society (ERS)
Date: 04-2017
Publisher: Informa UK Limited
Date: 06-2022
DOI: 10.2147/NSS.S362205
Publisher: Elsevier BV
Date: 05-2020
Publisher: Wiley
Date: 12-2012
DOI: 10.1038/OBY.2012.120
Publisher: Wiley
Date: 29-07-2018
DOI: 10.1113/JP275764
Publisher: Wiley
Date: 10-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: Frontiers Media SA
Date: 21-12-2018
Publisher: American Physiological Society
Date: 07-2007
DOI: 10.1152/JAPPLPHYSIOL.01618.2005
Abstract: Inspiratory load compensation is impaired in patients with obstructive sleep apnea (OSA), a condition characterized by hypoxia during sleep. We sought to compare the effects of sustained hypoxia on ventilation during inspiratory resistive loading in OSA patients and matched controls. Ten OSA patients and 10 controls received 30 min of isocapnic hypoxia (arterial oxygen saturation 80%) and normoxia in random order. Following the gas period, subjects were administered six incremental 2-min inspiratory resistive loads while breathing room air. Ventilation was measured throughout the loading period. In both patients and controls, there was a significant increase in inspiratory time with increasing load ( P = 0.006 and 0.003, respectively), accompanied by a significant fall in peak inspiratory flow ( P = 0.006 and P 0.001, respectively). The result was a significant fall in minute ventilation in both groups with increasing load ( P = 0.003 and P 0.001, respectively). There was no difference between the two groups for these parameters. The only difference between the two groups was a transient increase in tidal volume in controls ( P = 0.02) but not in OSA patients ( P = 0.57) during loading. Following hypoxia, there was a significant increase in minute ventilation during loading in both groups ( P 0.001). These results suggest that ventilation during incremental resistive loading is preserved in OSA patients and that it appears relatively impervious to the effects of hypoxia.
Publisher: American Physiological Society
Date: 11-2019
DOI: 10.1152/JAPPLPHYSIOL.00660.2018
Abstract: Tracheal displacement is thought to be the primary mechanism by which changes in lung volume influence upper airway patency. Caudal tracheal displacement during inspiration may help preserve the integrity of the upper airway in response to increasing negative airway pressure by stretching and stiffening pharyngeal tissues. However, tracheal displacement has not been previously quantified in obstructive sleep apnea (OSA). Accordingly, we aimed to measure tracheal displacements in awake in iduals with and without OSA. The upper head and neck of 34 participants [apnea-hypopnea index (AHI) = 2–74 events/h] were imaged in the midsagittal plane using dynamic magnetic resonance imaging (MRI) during supine awake quiet breathing. MRI data were analyzed to identify peak tracheal displacement and its timing relative to inspiration. Epiglottic pressure was measured separately for a subset of participants ( n = 30) during similar experimental conditions. Nadir epiglottic pressure and its timing relative to inspiration were quantified. Peak tracheal displacement ranged from 1.0–9.6 mm, with a median (25th–75th percentile) of 2.3 (1.7–3.5) mm, and occurred at 89 (78–99)% of inspiratory time. Peak tracheal displacement increased with increasing OSA severity (AHI) ( R 2 = 0.28, P = 0.013) and increasing negative nadir epiglottic pressure ( R 2 = 0.47, P = 0.023). Relative inspiratory timing of peak tracheal displacement also correlated with OSA severity, with peak displacement occurring earlier in inspiration with increasing AHI ( R 2 = 0.36, P = 0.002). Tracheal displacements during quiet breathing are larger in in iduals with more severe OSA and tend to reach peak displacement earlier in the inspiratory cycle. Increased tracheal displacement may contribute to maintenance of upper airway patency during wakefulness in OSA, particularly in those with severe disease. NEW & NOTEWORTHY Tracheal displacement is thought to play an important role in stabilizing the upper airway by stretching/stiffening the pharyngeal musculature. Using dynamic magnetic resonance imaging, this study shows that caudal tracheal displacement is more pronounced during inspiration in obstructive sleep apnea (OSA) compared with healthy in iduals. Softer pharyngeal muscles and greater inspiratory forces in OSA may underpin greater tracheal excursion. These findings suggest that tracheal displacement may contribute to maintenance of pharyngeal patency during wakefulness in OSA.
Publisher: American Thoracic Society
Date: 03-2022
Publisher: Oxford University Press (OUP)
Date: 03-2016
DOI: 10.5665/SLEEP.5516
Publisher: American Physiological Society
Date: 15-05-2015
DOI: 10.1152/JAPPLPHYSIOL.01103.2014
Abstract: This study assessed the effects of inhaled lignocaine to reduce upper airway surface mechanoreceptor activity on 1) basal genioglossus and tensor palatini EMG, 2) genioglossus reflex responses to large pulses (∼10 cmH 2 O) of negative airway pressure, and 3) upper airway collapsibility in 15 awake in iduals. Genioglossus and tensor palatini muscle EMG and airway pressures were recorded during quiet nasal breathing and during brief pulses (250 ms) of negative upper-airway pressure. Lignocaine reduced peak inspiratory (5.6 ± 1.5 vs. 3.8 ± 1.1% maximum mean ± SE, P 0.01) and tonic (2.8 ± 0.8 vs. 2.1 ± 0.7% maximum P 0.05) genioglossus EMG during quiet breathing but had no effect on tensor palatini EMG (5.0 ± 0.8 vs. 5.0 ± 0.5% maximum P = 0.97). Genioglossus reflex excitation to negative pressure pulses decreased after anesthesia (60.9 ± 20.7 vs. 23.6 ± 5.2 μV P 0.05), but not when expressed as a percentage of the immediate prestimulus baseline. Reflex excitation was closely related to the change in baseline EMG following lignocaine ( r 2 = 0.98). A short-latency genioglossus reflex to rapid increases from negative to atmospheric pressure was also observed. The upper airway collapsibility index (%difference) between nadir choanal and epiglottic pressure increased after lignocaine (17.8 ± 3.7 vs. 28.8 ± 7.5% P 0.05). These findings indicate that surface receptors modulate genioglossus but not tensor palatini activity during quiet breathing. However, removal of input from surface mechanoreceptors has minimal effect on genioglossus reflex responses to large (∼10 cmH 2 O), sudden changes in airway pressure. Changes in pressure rather than negative pressure per se can elicit genioglossus reflex responses. These findings challenge previous views and have important implications for upper airway muscle control.
Publisher: Wiley
Date: 13-10-2023
DOI: 10.1111/JSR.14051
Publisher: Oxford University Press (OUP)
Date: 05-2012
DOI: 10.5665/SLEEP.1834
Publisher: Oxford University Press (OUP)
Date: 21-09-2020
Abstract: To characterize how mandibular advancement splint (MAS) alters inspiratory tongue movement in people with obstructive sleep apnea (OSA) during wakefulness and whether this is associated with MAS treatment outcome. A total of 87 untreated OSA participants (20 women, apnea–hypopnea index (AHI) 7–102 events/h, aged 19–76 years) underwent a 3T MRI with a MAS in situ. Mid-sagittal tagged images quantified inspiratory tongue movement with the mandible in a neutral position and advanced to 70% of the maximum. Movement was quantified with harmonic phase methods. Treatment outcome was determined after at least 9 weeks of therapy. A total of 72 participants completed the study: 34 were responders (AHI & 5 or AHI ≤ 10events/h with & % reduction in AHI), 9 were partial responders (& % reduction in AHI but AHI & 10 events/h), and 29 nonresponders (change in AHI & % and AHI ≥ 10 events/h). About 62% (45/72) of participants had minimal inspiratory tongue movement (& mm) in the neutral position, and this increased to 72% (52/72) after advancing the mandible. Mandibular advancement altered inspiratory tongue movement pattern for 40% (29/72) of participants. When tongue dilatory patterns altered with advancement, 80% (4/5) of those who changed to a counterproductive movement pattern (posterior movement & mm) were nonresponders and 71% (5/7) of those who changed to beneficial (anterior movement & mm) were partial or complete responders. The mandibular advancement action on upper airway dilator muscles differs between in iduals. When mandibular advancement alters inspiratory tongue movement, therapeutic response to MAS therapy was more common among those who convert to a beneficial movement pattern.
Publisher: Oxford University Press (OUP)
Date: 03-2009
Publisher: American Physiological Society
Date: 15-04-2014
DOI: 10.1152/JAPPLPHYSIOL.00853.2013
Abstract: 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. Eight subjects [4 obstructive sleep apnea (OSA), 4 controls] slept in an “iron lung” and wore a nasal mask connected to a continuous/bilevel positive airway pressure machine. Downstream pressure was measured using an epiglottic catheter. During non-rapid eye movement (NREM) sleep, subjects were hyperventilated to produce a central apnea, then extrathoracic pressure was decreased slowly (∼2–4 s) or abruptly ( .5 s) to lower downstream pressure and create inspiratory airflow. Pressure-flow curves were constructed for flow-limited breaths, and slow vs. fast reductions in downstream pressure were compared. All subjects exhibited an initial peak and then a decrease in flow with more negative pressures, demonstrating negative effort dependence (NED). The rate of change in downstream pressure did not affect the peak to plateau airflow ratio: %NED 22 ± 13% (slow) vs. 20 ± 5% (fast), P = not significant. We conclude that the initial peak in inspiratory airflow is not a transient but rather a distinct mechanical property of the upper airway. In contrast to the classical Starling resistor model, the upper airway exhibits marked NED in some subjects.
Publisher: American Physiological Society
Date: 03-2022
DOI: 10.1152/JAPPLPHYSIOL.00240.2021
Abstract: Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have "typical" anatomical risk factors (i.e., nonobese and female predominance). Accordingly, nonanatomical factors such as impaired upper-airway muscle function may be particularly important for OSA pathogenesis in MS. Therefore, this study aimed to investigate genioglossus (largest upper-airway dilator muscle) reflex responses to brief pulses of upper-airway negative pressure in people with OSA and MS. Eleven people with MS and OSA and 10 OSA controls without MS matched for age, sex, and OSA severity were fitted with a nasal mask, pneumotachograph, choanal and epiglottic pressure sensors, and intramuscular electrodes into genioglossus. Approximately 60 brief (250 ms) negative pressure pulses (approximately -12 cmH
Publisher: Oxford University Press (OUP)
Date: 27-12-2019
DOI: 10.1093/SLEEP/ZSY261
Abstract: Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans. Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design. Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p & 0.001). Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea. Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, trial ID: ACTRN12616000469415.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2008
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/JSR.19_12765
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-02-2020
DOI: 10.5664/JCSM.8184
Publisher: Future Medicine Ltd
Date: 04-2014
DOI: 10.2217/EBO.13.343
Publisher: Wiley
Date: 14-07-2021
DOI: 10.1113/JP281912
Abstract: Recent animal and human physiology studies indicate that noradrenergic and muscarinic processes are key mechanisms that mediate pharyngeal muscle control during sleep. The noradrenergic agent reboxetine combined with the anti‐muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy in iduals. However, whether these findings translate to the clinically relevant patient population of people with obstructive sleep apnoea (OSA), and the effects of the agents on OSA severity, are unknown. We found that reboxetine plus hyoscine butylbromide reduced OSA severity, including overnight hypoxaemia, via increases in pharyngeal muscle responsiveness, improvements in respiratory control and airway collapsibility without changing the respiratory arousal threshold. These findings provide mechanistic insight into the role of noradrenergic and anti‐muscarinic agents on upper airway stability and breathing during sleep and are important for pharmacotherapy development for OSA. The noradrenergic agent reboxetine combined with the anti‐muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy in iduals. However, the effects of this drug combination on obstructive sleep apnoea (OSA) severity are unknown. Accordingly, this study aimed to determine if reboxetine plus hyoscine butylbromide reduces OSA severity. Secondary aims were to investigate the effects on key upper airway physiology and endotypic traits. Twelve people with OSA aged 52 ± 13 years, BMI = 30 ± 5 kg/m 2 , completed a double‐blind, randomised, placebo‐controlled, crossover trial (ACTRN12617001326381). Two in‐laboratory sleep studies with nasal mask, pneumotachograph, epiglottic pressure sensor and bipolar fine‐wire electrodes into genioglossus and tensor palatini muscles were performed separated by approximately 1 week. Each participant received either reboxetine (4 mg) plus hyoscine butylbromide (20 mg), or placebo immediately prior to sleep. Polysomnography, upper airway physiology and endotypic estimates of OSA were compared between conditions. Reboxetine plus hyoscine butylbromide reduced the apnoea/hypopnoea index by (mean ± SD) 17 ± 17 events/h from 51 ± 30 to 33 ± 22 events/h ( P = 0.005) and nadir oxygen saturation increased by 6 ± 5% from 82 ± 5 to 88 ± 2% ( P = 0.002). The drug combination increased tonic genioglossus muscle responsiveness during non‐REM sleep (median [25th, 75th centiles]: −0.007 [−0.0004, −0.07] vs . −0.12 [−0.02, −0.40] %maxEMG/cmH 2 O, P = 0.02), lowered loop gain (0.43 ± 0.06 vs . 0.39 ± 0.07, P = 0.01), and improved airway collapsibility (90 [69, 95] vs . 93 [88, 96] %eupnoea, P = 0.02), without changing the arousal threshold ( P = 0.39). These findings highlight the important role that noradrenergic and muscarinic processes have on upper airway function during sleep and the potential for pharmacotherapy to target these mechanisms to treat OSA.
Publisher: American Physiological Society
Date: 12-2011
DOI: 10.1152/JAPPLPHYSIOL.00653.2011
Abstract: Numerous studies have demonstrated upper-airway neuromuscular abnormalities during wakefulness in snorers and obstructive sleep apnea (OSA) patients. However, the functional role of sensorimotor impairment in OSA pathogenesis/disease progression and its potential effects on protective upper-airway reflexes, measures of respiratory sensory processing, and force characteristics remain unclear. This study aimed to gain physiological insight into the potential role of sensorimotor impairment in OSA pathogenesis/disease progression by comparing sensory processing properties (respiratory-related evoked potentials RREP), functionally important protective reflexes (genioglossus and tensor palatini) across a range of negative pressures (brief pulses and entrained iron lung ventilation), and tongue force and time to task failure characteristics between 12 untreated OSA patients and 13 controls. We hypothesized that abnormalities in these measures would be present in OSA patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 ± 1 vs. 19 ± 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 ± 2 vs. 25 ± 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus activity during iron lung ventilation (−0.68 ± 1.0 vs. −0.80 ± 2.0 cmH 2 O/%max, P = 0.59) were not different between patients and controls. Maximal tongue protrusion force was greater in OSA patients vs. controls (35 ± 2 vs. 27 ± 2 N, P 0.01), but task failure occurred more rapidly (149 ± 24 vs. 254 ± 23 s, P 0.01). Upper-airway protective reflexes across a range of negative pressures as measured by electromyography and the early P1 component of the RREP are preserved in OSA patients during wakefulness. Consistent with an adaptive training effect, tongue protrusion force is increased, not decreased, in untreated OSA patients. However, OSA patients may be vulnerable to fatigue of upper-airway dilator muscles, which could contribute to disease progression.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.RESP.2021.103786
Abstract: Genioglossus was stimulated intramuscularly to determine the effect of regional activation of the muscle on tongue movement in eight healthy adults. Stimulation at motor threshold was delivered with a needle electrode inserted to different depths in the anterior and posterior regions of genioglossus. The current litude that induced muscle contraction was ∼80% higher for anterior than posterior sites. Evoked tongue movements were determined from stimulus-triggered averages (150 pulses) of the outputs from an accelerometer fixed to the posterosuperior surface of the tongue. The median litude [95% confidence intervals] for the resultant acceleration was 0.0 m/s
Publisher: MDPI AG
Date: 20-03-2020
Abstract: Introduction: The anatomical collapsibility of the upper airway, neuromuscular tone and function, sleep–wake and ventilatory control instability, and the arousal threshold all interact and contribute to certain pathophysiologic features that characterize different types of obstructive sleep apnea (OSA). A model of qualitative phenotypizationallowsus to characterize the different pathophysiological traits in OSA patients.Methods: A narrative review was performed, to analyze the available literature evidence, with the purpose of generating a model of qualitative phenotypization to characterize pathophysiological traits in patients with OSA.Results: 96 out of 3829 abstracts were selected for full-text review. Qualitative phenotyping model of OSA:Data concerning the OSA qualitative pathophysiological traits’ measurement can be deducted by means of clinical PSG, grade of OSA severity, and therapeutic level of Continuous Positive Airway Pressure (CPAP) and are reported in the text. This approach would allow qualitative phenotyping with widely accessible methodology in a routine clinical scenario and is of particular interest for the sleep specialist, surgical treatment decision-making, and customized OSA multimodality treatment.
Publisher: Oxford University Press (OUP)
Date: 29-05-2019
DOI: 10.1093/SLEEP/ZSZ119
Abstract: Mandibular advancement splint (MAS) therapy is a well-tolerated alternative to continuous positive airway pressure for obstructive sleep apnea (OSA). Other therapies, including nasal expiratory positive airway pressure (EPAP) valves, can also reduce OSA severity. However, % of patients have an incomplete or no therapeutic response with either therapy alone and thus remain at risk of adverse health outcomes. Combining these therapies may yield greater efficacy to provide a therapeutic solution for many incomplete/nonresponders to MAS therapy. Thus, this study evaluated the efficacy of combination therapy with MAS plus EPAP in incomplete/nonresponders to MAS alone. Twenty-two people with OSA (apnea–hypopnea index [AHI] = 22 [13, 42] events/hr), who were incomplete/nonresponders (residual AHI 5 events/hr) on an initial split-night polysomnography with a novel MAS device containing an oral airway, completed an additional split-night polysomnography with MAS + oral EPAP valve and MAS + oral and nasal EPAP valves (order randomized). Compared with MAS alone, MAS + oral EPAP significantly reduced the median total AHI, with further reductions with the MAS + oral/nasal EPAP combination (15 [10, 34] vs. 10 [7, 21] vs. 7 [3, 13] events/hr, p 0.01). Larger reductions occurred in supine nonrapid eye movement AHI with MAS + oral/nasal EPAP combination therapy (ΔAHI = 23 events/hr, p 0.01). OSA resolved (AHI 5 events/hr) with MAS + oral/nasal EPAP in nine in iduals and 13 had ≥50% reduction in AHI from no MAS. However, sleep efficiency was lower with MAS + oral/nasal EPAP versus MAS alone or MAS + oral EPAP (78 ± 19 vs. 87 ± 10 and 88 ± 10% respectively, p 0.05). Combination therapy with a novel MAS device and simple oral or oro-nasal EPAP valves reduces OSA severity to therapeutic levels for a substantial proportion of incomplete/nonresponders to MAS therapy alone. Name: Targeted combination therapy: Physiological mechanistic studies to inform treatment for obstructive sleep apnea (OSA) URL: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372279 Registration: ACTRN12617000492358 (Part C)
Publisher: European Respiratory Society (ERS)
Date: 07-2020
DOI: 10.1183/23120541.00093-2020
Abstract: The concurrent use of sedating centrally acting drugs and opioids by chronic pain patients occurs routinely despite concerns of negative impacts on respiration during sleep. The effects of centrally acting drugs and opioids on sleep apnoea have not been well characterised. The objective of this study was to assess the effect of concomitant centrally acting drugs and opioids on the prevalence and severity of sleep apnoea in chronic pain patients. We conducted a prospective cohort study at five chronic pain clinics. Each participant underwent an in-laboratory polysomnography and daily morphine milligram equivalents were calculated. Participants were grouped into centrally acting drugs and opioid users versus sole opioid users. Of the 332 consented participants, 204 underwent polysomnography and 120 (58.8%) had sleep apnoea (72% obstructive, 20% central, and 8% indeterminate sleep apnoea). Overall, 35% (71 of 204) were taking opioids alone, and 65% (133 of 204) were taking centrally acting drugs and opioids. There was a 69% decrease in the odds of having sleep apnoea (apnoea–hypopnoea index ≥5 events·h −1 ) in participants taking benzodiazepine/opioids versus sole opioid users (OR 0.31, 95% CI:0.12–0.80, p=0.015). Additionally, concomitant benzodiazepine/opioids versus sole opioid use was associated with a decrease in respiratory arousal index scores (p=0.03). Mean overnight S pO 2 was approximately 1% lower in the concomitant benzodiazepine/opioids group versus sole opioid users (93.1±2.5 versus 94.4±2.1%, p=0.01). In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-02-2014
DOI: 10.5664/JCSM.3450
Publisher: Oxford University Press (OUP)
Date: 13-04-2017
DOI: 10.1093/SLEEP/ZSX056
Publisher: American Thoracic Society
Date: 15-06-2017
Publisher: Elsevier BV
Date: 03-2013
Publisher: American Physiological Society
Date: 02-2014
DOI: 10.1152/JAPPLPHYSIOL.00649.2013
Abstract: Historically, brief awakenings from sleep (cortical arousals) have been assumed to be vitally important in restoring airflow and blood-gas disturbances at the end of obstructive sleep apnea (OSA) breathing events. Indeed, in patients with blunted chemical drive (e.g., obesity hypoventilation syndrome) and in instances when other defensive mechanisms fail, cortical arousal likely serves an important protective role. However, recent insight into the pathogenesis of OSA indicates that a substantial proportion of respiratory events do not terminate with a cortical arousal from sleep. In many cases, cortical arousals may actually perpetuate blood-gas disturbances, breathing instability, and subsequent upper airway closure during sleep. This brief review summarizes the current understanding of the mechanisms mediating respiratory-induced cortical arousal, the physiological factors that influence the propensity for cortical arousal, and the potential dual roles that cortical arousal may play in OSA pathogenesis. Finally, the extent to which existing sedative agents decrease the propensity for cortical arousal and their potential to be therapeutically beneficial for certain OSA patients are highlighted.
Publisher: Oxford University Press (OUP)
Date: 04-04-2019
DOI: 10.1093/SLEEP/ZSZ080
Abstract: A collapsible or crowded pharyngeal airway is the main cause of obstructive sleep apnea (OSA). However, quantification of airway collapsibility during sleep (Pcrit) is not clinically feasible. The primary aim of this study was to compare upper airway collapsibility using a simple wakefulness test with Pcrit during sleep. Participants with OSA were instrumented with a nasal mask, pneumotachograph and two pressure sensors, one at the choanae (PCHO), the other just above the epiglottis (PEPI). Approximately 60 brief (250 ms) pulses of negative airway pressure (~ –12 cmH2O at the mask) were delivered in early inspiration during wakefulness to measure the upper airway collapsibility index (UACI). Transient reductions in the continuous positive airway pressure (CPAP) holding pressure were then performed during sleep to determine Pcrit. In a subset of participants, the optimal number of replicate trials required to calculate the UACI was assessed. The UACI (39 ± 24 mean ± SD range = 0%–87%) and Pcrit (–0.11 ± 2.5 range: –4 to +5 cmH2O) were quantified in 34 middle-aged people (9 female) with varying OSA severity (apnea–hypopnea index range = 5–92 events/h). The UACI at a mask pressure of approximately –12 cmH2O positively correlated with Pcrit (r = 0.8 p 0.001) and could be quantified reliably with as few as 10 replicate trials. The UACI performed well at discriminating in iduals with subatmospheric Pcrit values [receiver operating characteristic curve analysis area under the curve = 0.9 (0.8–1), p 0.001]. These findings indicate that a simple wakefulness test may be useful to estimate the extent of upper airway anatomical impairment during sleep in people with OSA to direct targeted non-CPAP therapies for OSA.
Publisher: Springer Science and Business Media LLC
Date: 30-03-2023
DOI: 10.1038/S41746-023-00801-2
Abstract: Obstructive sleep apnea (OSA) severity can vary markedly from night-to-night. However, the impact of night-to-night variability in OSA severity on key cardiovascular outcomes such as hypertension is unknown. Thus, the primary aim of this study is to determine the effects of night-to-night variability in OSA severity on hypertension likelihood. This study uses in-home monitoring of 15,526 adults with ~180 nights per participant with an under-mattress sleep sensor device, plus ~30 repeat blood pressure measures. OSA severity is defined from the mean estimated apnea–hypopnoea index (AHI) over the ~6-month recording period for each participant. Night-to-night variability in severity is determined from the standard deviation of the estimated AHI across recording nights. Uncontrolled hypertension is defined as mean systolic blood pressure ≥140 mmHg and/or mean diastolic blood pressure ≥90 mmHg. Regression analyses are performed adjusted for age, sex, and body mass index. A total of 12,287 participants (12% female) are included in the analyses. Participants in the highest night-to-night variability quartile within each OSA severity category, have a 50–70% increase in uncontrolled hypertension likelihood versus the lowest variability quartile, independent of OSA severity. This study demonstrates that high night-to-night variability in OSA severity is a predictor of uncontrolled hypertension, independent of OSA severity. These findings have important implications for the identification of which OSA patients are most at risk of cardiovascular harm.
Publisher: American Thoracic Society
Date: 15-11-2011
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/JSR.36_12765
Publisher: Wiley
Date: 04-10-2016
DOI: 10.1111/RESP.12913
Abstract: Obstructive sleep apnoea (OSA) is a common disorder caused by not only an impaired upper airway anatomy (i.e. anatomically narrow/collapsible airway), but also by several non-anatomical factors. In this review, we summarise what is known about how each of the pathological factors that cause OSA vary according to disease severity as measured by the apnoea-hypopnoea index. Our synthesis of the available literature indicates that most of the key factors that cause OSA vary with disease severity. However, there is substantial heterogeneity such that the relative contribution of each of these traits varies both between patients and within different severities of disease. These differences likely contribute to variable efficacy of many non-continuous positive airway pressure treatments and inconsistencies in responses with regard to different OSA severities at baseline.
Publisher: American Thoracic Society
Date: 11-2019
Publisher: Oxford University Press (OUP)
Date: 03-2016
DOI: 10.5665/SLEEP.5522
Publisher: European Respiratory Society (ERS)
Date: 07-2018
DOI: 10.1183/13993003.00149-2018
Abstract: Hypnotic use in obstructive sleep apnoea (OSA) is contraindicated due to safety concerns. Recent studies indicate that single-night hypnotic use worsens hypoxaemia in some and reduces OSA severity in others depending on differences in pathophysiology. However, longer clinical trial data are lacking. This study aimed to determine the effects of 1 month of zopiclone on OSA severity, sleepiness and alertness in patients with low–moderate respiratory arousal thresholds without major overnight hypoxaemia. 69 participants completed a physiology screening night with an epiglottic catheter to quantify arousal threshold. 30 eligible patients (apnoea–hypopnoea index (AHI) 22±11 events·h −1 ) then completed standard in-laboratory polysomnography (baseline) and returned for two additional overnight sleep studies (nights 1 and 30) after receiving either nightly zopiclone (7.5 mg) or placebo during a 1-month, double-blind, randomised, parallel trial ( ANZCTR identifier ANZCTRN12613001106729). The change in AHI from baseline to night 30 was not different between zopiclone versus placebo groups (−5.9±10.2 versus −2.4±5.5 events·h −1 p=0.24). Similarly, hypoxaemia, next-day sleepiness and driving simulator performance were not different. 1 month of zopiclone does not worsen OSA severity, sleepiness or alertness in selected patients without major overnight hypoxaemia. As the first study to assess the effect of a hypnotic on OSA severity and sleepiness beyond single-night studies, these findings provide important safety data and insight into OSA pathophysiology.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-11-2016
DOI: 10.5664/JCSM.6272
Publisher: Frontiers Media SA
Date: 2012
Publisher: Wiley
Date: 25-04-2018
DOI: 10.1113/JP275222
Publisher: American Thoracic Society
Date: 04-2021
Publisher: Proceedings of the National Academy of Sciences
Date: 30-03-2020
Abstract: Spontaneous arousals from sleep are associated with tachycardia and blood pressure responses excessive to physiological need. The prevailing view is that stereotyped autonomic activity is generated by feedforward inputs from cortical and subcortical systems implicated in the arousal, akin to autonomic activation with emotional behavior or cognitive effort. This remains an inadequate explanation, and mechanisms that augment arousal and autonomic functions in sleep remain enigmatic. We identified that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Nocturnal swallowing and glottic adduction—essential airway defense mechanisms—were also causally linked to prolonged, intense arousals. These findings identify a fundamental mechanism driving both autonomic activation and heightened arousal via cortical feedback from brainstem swallow networks.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-01-2017
DOI: 10.5664/JCSM.6394
Publisher: American Thoracic Society
Date: 15-01-2022
Publisher: BMJ
Date: 02-2010
Publisher: BMJ
Date: 30-08-2018
DOI: 10.1136/THORAXJNL-2018-211675
Abstract: Anaesthesiology guidelines suggest that opioids worsen obstructive sleep apnoea (OSA) despite no randomised controlled trial evidence. We therefore conducted a randomised controlled trial to evaluate the effects of a common clinical dose of morphine on OSA, and to identify clinical phenotype and genotype vulnerability to opioid-respiratory depression. Under a double-blind, randomised, crossover design, 60 male patients with OSA attended two visits to the hospital sleep laboratory, at least 1 week apart. Either 40 mg controlled-release oral morphine or placebo was administered. Awake ventilatory chemoreflex tests were performed post dose and prior to overnight polysomnography monitoring. Blood was s led before sleep and the next morning for toxicology and genotype analyses. Sleep time with oxygen saturation (SpO 2 ) % (T90) was the primary outcome. Despite a large inter-in idual variability, 40 mg morphine did not worsen T90 and apnoea–hypopnoea index, and only decreased the SpO 2 nadir by 1.3%. In patients with severe OSA, a lower baseline CO 2 ventilatory response threshold correlated with the worsening of T90, apnoea–hypopnoea index and oxygen desaturation index with morphine use. Patients with OSA and the A118G OPRM1 polymorphism of A/A and A/G had a significantly different morphine effect on awake ventilatory chemosensitivity and T90 during sleep. 40 mg oral controlled-release morphine did not worsen OSA in men, challenging traditional thinking that OSA will be worsened by opioids. In idual opioid response in patients with OSA may relate to baseline CO 2 response threshold and OPRM1 genotype. Our study findings may pave the way for a precision medicine approach to avoid opioid-related risks. The Australian and New Zealand Clinical Trial Registry, ACTRN12613000858796.
Publisher: American Physiological Society
Date: 11-2023
Publisher: Wiley
Date: 10-2018
Publisher: Oxford University Press (OUP)
Date: 2015
DOI: 10.5665/SLEEP.4324
Publisher: American Thoracic Society
Date: 15-10-2013
Publisher: Oxford University Press (OUP)
Date: 11-2016
DOI: 10.5665/SLEEP.6226
Publisher: Oxford University Press (OUP)
Date: 04-2014
DOI: 10.5665/SLEEP.3596
Publisher: American Thoracic Society
Date: 02-2014
Publisher: Wiley
Date: 10-2019
DOI: 10.1111/JSR.12773
Abstract: Pharyngeal and oesophageal manometry is used clinically and in research to quantify respiratory effort, upper-airway mechanics and the pathophysiological contributors to obstructive sleep apnea. However, the effects of this equipment on respiratory events and sleep in obstructive sleep apnea are unclear. As part of a clinical trial (ANZCTRN12613001106729), data from 28 participants who successfully completed a physiology night with an epiglottic catheter and nasal mask followed by a standard in-laboratory polysomnography were compared. The apnea-hypopnea index was not different during the physiology night versus standard polysomnography (22 ± 14 versus 23 ± 13 events per hr, p = 0.71). Key sleep parameters were also not different compared between conditions, including sleep efficiency (79 ± 13 versus 81 ± 11%, p = 0.31) and the arousal index (26 ± 11 versus 27 ± 11 arousals per hr, p = 0.83). There were, however, sleep stage distribution changes between nights with less N3 and rapid eye movement sleep and more N1 on the physiology night, with no difference in N2 (53 ± 15 versus 48 ± 9, p = 0.08). However, these changes did not increase next-day sleepiness. These findings indicate that while minor sleep stage distribution changes do occur towards lighter sleep, epiglottic manometry does not alter obstructive sleep apnea severity or sleep efficiency. Thus, epiglottic manometry can be used clinically and to collect detailed physiological information for research without major sleep disruption.
Publisher: Elsevier BV
Date: 12-2023
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-04-2020
DOI: 10.5664/JCSM.8244
Publisher: European Respiratory Society (ERS)
Date: 06-10-2016
DOI: 10.1183/13993003.00823-2016
Abstract: 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. Pharyngeal collapsibility (critical collapsing pressure of the upper airway ( P crit )) and ventilation under both passive ( V′ 0,passive ) and active ( V′ 0,active ) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP. Desipramine reduced active P crit (median (interquartile range) −5.2 (4.3) cmH 2 O on desipramine versus −1.9 (2.7) cmH 2 O on placebo p=0.049) but not passive P crit (−2.2 (3.4) versus −0.7 (2.1) cmH 2 O p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined as V′ 0,active − V′ 0,passive ) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009). In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.
Publisher: American Thoracic Society
Date: 12-2014
Publisher: American Thoracic Society
Date: 15-04-2022
Publisher: American Thoracic Society
Date: 15-12-2003
Publisher: European Respiratory Society (ERS)
Date: 23-12-2010
Publisher: BMJ
Date: 07-2017
Publisher: Elsevier BV
Date: 05-2016
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/JSR.66_12765
Publisher: Elsevier BV
Date: 02-2018
Publisher: Oxford University Press (OUP)
Date: 29-07-2021
Abstract: To investigate the effect of upper airway fat composition on tongue inspiratory movement and obstructive sleep apnea (OSA). Participants without or with untreated OSA underwent a 3T magnetic resonance imaging (MRI) scan. Anatomical measurements were obtained from T2-weighted images. Mid-sagittal inspiratory tongue movements were imaged using tagged MRI during wakefulness. Tissue volumes and percentages of fat were quantified using an mDIXON scan. Forty predominantly overweight participants with OSA were compared to 10 predominantly normal weight controls. After adjusting for age, BMI, and gender, the percentage of fat in the tongue was not different between groups (analysis of covariance [ANCOVA], p = 0.45), but apnoeic patients had a greater tongue volume (ANCOVA, p = 0.025). After adjusting for age, BMI, and gender, higher OSA severity was associated with larger whole tongue volume (r = 0.51, p & 0.001), and greater dilatory motion of the anterior horizontal tongue compartment (r = −0.33, p = 0.023), but not with upper airway fat percentage. Higher tongue fat percentage was associated with higher BMI and older age (Spearman r = 0.43, p = 0.002, and r =0.44, p = 0.001, respectively), but not with inspiratory tongue movements. Greater inspiratory tongue movement was associated with larger tongue volume (e.g. horizontal posterior compartment, r = −0.44, p = 0.002) and smaller nasopharyngeal airway (e.g. oblique compartment, r = 0.29, p = 0.040). Larger tongue volume and a smaller nasopharynx are associated with increased inspiratory tongue dilation during wakefulness in people with and without OSA. This compensatory response was not influenced by higher tongue fat content. Whether this is also true in more obese patient populations requires further investigation.
Publisher: Oxford University Press (OUP)
Date: 26-02-2022
Abstract: To characterize how mandibular advancement enlarges the upper airway via posterior tongue advancement in people with obstructive sleep apnea (OSA) and whether this is associated with mandibular advancement splint (MAS) treatment outcome. One-hundred and one untreated people with OSA underwent a 3T magnetic resonance (MRI) scan. Dynamic mid-sagittal posterior tongue and mandible movements during passive jaw advancement were measured with tagged MRI. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of maximum advancement. Treatment outcome was determined after a minimum of 9 weeks of therapy. Seventy-one participants completed the study: 33 were responders (AHI 50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 nonresponders (AHI reduction 4 mm). In comparison, a model using only baseline AHI correctly classified 50.0% of patients (5-fold cross-validated 52.5%, n = 40). Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improve treatment response categorization to a satisfactory level (69.2%, 5-fold cross-validated 62.5%).
Publisher: Elsevier
Date: 2013
Publisher: American Thoracic Society
Date: 11-2020
Publisher: Oxford University Press (OUP)
Date: 10-2010
Publisher: American Physiological Society
Date: 05-2008
DOI: 10.1152/JAPPLPHYSIOL.01056.2007
Abstract: Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wakefulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19–42 yr old, were studied on two separate occasions, ∼1 wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface electrodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation ∼85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately −10 cmH 2 O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative-pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by activation with more pronounced suppression during hypoxia compared with normoxia (mean ± SE suppression duration 64 ± 6 vs. 38 ± 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles.
Publisher: Oxford University Press (OUP)
Date: 31-01-2023
Publisher: Informa UK Limited
Date: 2018
DOI: 10.2147/NSS.S124657
Publisher: Portland Press Ltd.
Date: 07-03-2011
DOI: 10.1042/CS20100588
Abstract: Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to −15 cmH2O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO2 (arterial blood oxygen saturation) & %], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [−14.0 (−19.9 to −10.9) compared with −18.0 (−22.2 to −15.1) cmH2O P& .01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep P& .01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.RESP.2016.09.014
Abstract: Obstructive sleep apnoea (OSA) is highly prevalent in people with tetraplegia. Nasal congestion, a risk factor for OSA, is common in people with tetraplegia. The purpose of this study was to quantify objective and perceived nasal resistance and its stability over four separate days in people with tetraplegia and OSA (n=8) compared to able-bodied controls (n=6). Awake nasal resistance was quantified using gold standard choanal pressure recordings (days 1 and 4) and anterior rhinomanometry (all visits). Nasal resistance (choanal pressure) was higher in people with tetraplegia versus controls (5.3[6.5] vs. 2.1[2.4] cmH
Publisher: American Thoracic Society
Date: 15-10-2005
Publisher: American Physiological Society
Date: 12-2021
DOI: 10.1152/JAPPLPHYSIOL.00085.2021
Abstract: This study evaluated upper airway muscle function, breathing, and comfort across different HFNC flows and temperatures. There were no increases in genioglossus muscle activity at higher flows despite greater negative epiglottic pressure swings. Increasing negative pressure swings was associated with increasing discomfort in the nonheated mode. HFNC was associated with ∼7 cmH 2 O increase in positive airway pressure, which may be the primary mechanism for upper airway stability with HFNC rather than increases in pharyngeal muscle activity.
Publisher: Wiley
Date: 10-2018
Publisher: American Thoracic Society
Date: 07-04-2017
Publisher: Wiley
Date: 15-01-2020
DOI: 10.1113/JP278433
Publisher: American Physiological Society
Date: 06-2010
DOI: 10.1152/JAPPLPHYSIOL.01437.2009
Abstract: On the basis of recent reports, the genioglossus (GG) negative-pressure reflex consists initially of excitation followed by a secondary state-dependent suppression phase. The mechanistic origin and functional role of GG suppression is unknown but has been hypothesized to arise from transient inhibition of respiratory active neurons as a protective reflex to prevent aspiration, as observed in other respiratory muscles (e.g., diaphragm) during airway occlusion. Unlike GG, tensor palatini (TP) is a tonic muscle with minimal respiratory phasic activation during relaxed breathing, although both muscles are important in preserving pharyngeal patency. This study aimed to compare GG vs. TP reflex responses to the same negative-pressure stimulus. We hypothesized that reflex suppression would be present in GG, but not TP. Intramuscular GG and TP EMGs were recorded in 12 awake, healthy subjects (6 female). Reflex responses were generated via 250-ms pulses of negative upper airway pressure (approximately −16 cmH 2 O mask pressure) delivered in early inspiration. GG and TP demonstrated reflex activation in response to negative pressure (peak latency 31 ± 4 vs. 31 ± 6 ms and peak litude 318 ± 55 vs. 314 ± 26% baseline, respectively). A secondary suppression phase was present in 8 of 12 subjects for GG (nadir latency 54 ± 7 ms, nadir litude 64 ± 6% baseline), but not in any subject for TP. These data provide further support for the presence of excitatory and inhibitory components of GG (phasic muscle) in response to brief upper airway negative-pressure pulses. Conversely, no reflex suppression below baseline was present in TP (tonic muscle) in response to the same stimuli. These differential responses support the hypothesis that GG reflex suppression may be mediated via inhibition of respiratory-related premotor input.
Publisher: Wiley
Date: 10-2018
Publisher: European Respiratory Society (ERS)
Date: 04-2020
DOI: 10.1183/23120541.00161-2020
Abstract: Insomnia and obstructive sleep apnoea (OSA) frequently co-occur and may be causally related through sleep fragmentation and/or hyperarousal mechanisms. Previous studies suggest that OSA treatment can improve insomnia severity. However, the effect of insomnia treatment on OSA severity has not been investigated. We performed a randomised controlled trial to investigate the effect of cognitive behavioural therapy for insomnia (CBTi) on OSA severity, controlling for potential sleep-stage and posture effects. 145 patients with comorbid insomnia (International Classification of Sleep Disorders, 3rd Edn) and untreated OSA (apnoea–hypopnoea index (AHI) ≥15 events·h −1 sleep) were randomised to a four-session CBTi programme or to a no-treatment control. Overnight sleep studies were completed pre- and post-treatment to measure AHI, arousal index and sleep architecture, to investigate the effect of intervention group, time, sleep stage (N1–3 or REM) and posture (supine or nonsupine) on OSA severity. The CBTi group showed a 7.5 event·h −1 greater AHI difference (mean (95% CI) decrease 5.5 (1.3–9.7) events·h −1 , Cohen's d =0.2, from 36.4 events·h −1 pre-treatment) across sleep-stages and postures, compared to control (mean increase 2.0 (−2.0–6.1) events·h −1 , d =0.01, from 37.5 events·h −1 at pre-treatment interaction p=0.012). Compared to control, the CBTi group also had a greater reduction in total number (mean difference 5.6 (0.6–10.6) greater overall reduction p=0.029) and duration of nocturnal awakenings (mean difference 21.1 (2.0–40.3) min greater reduction p=0.031) but showed no difference in the arousal index, or sleep architecture. CBTi consolidates sleep periods and promotes a 15% decrease in OSA severity in patients with comorbid insomnia and OSA. This suggests that insomnia disorder may exacerbate OSA and provides further support for treating insomnia in the presence of comorbid OSA.
Publisher: European Respiratory Society (ERS)
Date: 31-05-2016
No related grants have been discovered for Danny Eckert.