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Abstract: The upper airway in patients with obstructive sleep apnea (OSA) is thought to collapse during sleep at least in part, because of a sleep related reduction in upper airway dilator muscle activity. Therefore, a comprehensive understanding of the neural regulation of these muscles is warranted. The dilator muscles can be classified in two broad categories; those that have respiratory related activity and those that fire constantly throughout the respiratory cycle. The motor control of these two groups likely differs with the former receiving input from respiratory neurons and negative pressure reflex circuits. The activity of both muscle groups is reduced shortly after sleep onset, indicating that both receive input from brainstem neurons involved in sleep regulation. In the apnea patient, this may lead to pharyngeal airway collapse. This review briefly describes the currently proposed sleep and respiratory neural pathways and how these circuits interact with the upper airway dilator muscle motorneurones, including recent evidence from animal studies. [Copyright &y& Elsevier]

Background: Frequent electroencephalographic arousals or awakenings associated with periodic leg movements (PLM) might be responsible in part for the complaints of sleep disturbances made by patients treated with antidepressants. Past studies, however, have determined the effects of only certain limited antidepressants, generally in small numbers of subjects, and never in a head-to-head study. Methods: A total of 274 consecutive patients taking antidepressants and 69 control subjects not taking antidepressants met criteria among patients referred for overnight diagnostic polysomnography. Periodic leg movements were visually counted and the PLM index (PLMI) was calculated. Results: The venlafaxine and selective serotonin reuptake inhibitor (SSRI) groups had significantly higher mean PLMIs than control and bupropion groups. Periodic leg movement indexes at thresholds considered to be of potential clinical significance were more statistically prevalent in the SSRI and venlafaxine groups compared with the control and bupropion groups. The odds ratio of having a PLMI greater than 20 was 5.15 for the SSRI group and 5.24 for the venlafaxine group compared with the control group. Conclusions: Venlafaxine and SSRI-induced PLM are likely to be the result of enhanced serotonergic availability and secondarily decreased dopaminergic effects. The results of this study might assist in the selection of antidepressants, especially in patients with pronounced sleep complaints. [Copyright &y& Elsevier]

Obstructive sleep apnea (OSA) is a common disease with important neurocognitive and cardiovascular sequelae. Existing therapies are unsatisfactory, leading investigators to seek alternative forms of anatomic manipulation to influence pharyngeal mechanics. We have developed a two-dimensional computational model of the normal human upper airway based on signal averaging of MRI. Using the finite element method, we can perform various anatomic perturbations on the structure in order to assess the impact of these manipulations on pharyngeal mechanics and collapse. By design, the normal sleeping upper airway model collapses at -13 cm H2O. This closing pressure becomes more negative (ie, less collapsible) when we perform mandibular advancement (-21 cm H2O), palatal resection (-18 cm H2O), or palatal stiffening (-17 cm H2O). Where clinical data are available in the literature, the results of our model correspond reasonably well. Furthermore, our model provides information regarding the site of obstruction and provides hypotheses for clinical studies that can be undertaken in the future (eg, combination therapies). We believe that, in the future, finite element modeling will provide a useful tool to help advance our understanding of OSA and its response to various therapies. [ABSTRACT FROM AUTHOR]

Background: During most of the cruise, submarines are detached from their environment. Therefore, O[sub 2] levels are relatively low (19 kPa, 144 mm Hg) and CO[sub 2] levels are high (1 kPa, 7.6 mm Hg). There are, however, periods during ventilation of the submarine in which CO[sub 2] levels drop and O[sub 2] levels increase. The objective of this study was to determine whether these unique gas changes might result in sleep-disordered breathing in submariners. Methods and materials: The sleep of eight healthy soldiers was assessed three times: (1) control night, in submarine docking; (2) at the beginning of the cruise (reflecting acute exposure to gas changes); and (3) at the end of the cruise (chronic exposure to gas changes). Each night was divided to three parts because of different CO[sub 2] levels (secondary to ventilation of the submarine). Sleep and breathing were measured using the portable Watch PAT100 device (Itamar Medical, Ltd; Caesarea, Israel) to detect breathing abnormalities during sleep. Results: Sleep and breathing data were categorized according to four CO[sub 2] conditions: acute moderate (inhaled CO[sub 2] levels of 2.3 to 5 mm Hg during first 1 to 2 nights of the cruise); acute high (inhaled CO[sub 2] levels of 5 to 9.2 mm Hg during the first 1 to 2 nights of the cruise); chronic moderate (inhaled CO[sub 2] levels of 2.3 to 5 mm Hg during nights 9 to 10 of the cruise); and chronic high (inhaled CO[sub 2] levels of 5 to 9.2 mm Hg during nights 9 to 10 of the cruise). Respiratory disturbance index (RDI) was significantly higher in the chronic moderate CO[sub 2] condition than the chronic high condition (18.9/h vs 8/h, p < 0.005). RDI did not correlate with CO[sub 2] levels during the first nights of the cruise (R = -0.2, not significant), but significantly negatively correlated with it during the last nights of the cruise (R = -0.56, p < 0.05). Conclusions: We conclude that during an 11-day cruise, submariners adapt to high CO[sub 2] levels, as evidenced by the significant dependence of RDI on CO[sub 2] during the final but not initial days of the cruise. This adaptation resulted in a significant increase in RDI when CO[sub 2] levels declined during the later nights of the cruise. [ABSTRACT FROM AUTHOR]

Background: Although continuous positive airway pressure (CPAP) has become the standard of care in the treatment of obstructive sleep apnea (OSA), 2 systematic reviews have questioned its utility. Since the publication of these reviews, several randomized controlled trials have been reported. We, therefore, performed a meta-analysis to assess the effect of CPAP on subjective and objective sleepiness. Methods: We conducted a thorough literature search to identify all published randomized controlled trials of CPAP in patients with OSA. Meta-analyses were performed using a random-effects model. Statistical heterogeneity was assessed using the Q statistic. Results: Twelve trials of CPAP in patients with OSA meeting our inclusion criteria were found. The Epworth Sleepiness Scale score was reported in 11 studies (706 patients). A meta-analysis found that CPAP reduced the Epworth Sleepiness Scale score an average of 2.94 points more than placebo (P<.001). The heterogeneity (Q[sub 10] = 57.7, P<.001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study. Trials recruiting subjects with severe OSA plus sleepiness (mean apnea-hypopnea index, ≥30 events per hour; and mean Epworth Sleepiness Scale score, ≥11) had a greater decrease in the Epworth Sleepiness Scale score than the other studies (4.75 vs 1.10; P<.001). Objective measures of sleepiness were reported in 8 trials (482 subjects). Continuous positive airway pressure increased sleep onset latency by 0.93 minute (P = .04) more than placebo. Conclusions: Continuous positive airway pressure therapy significantly improves subjective and objective measures of sleepiness in patients with OSA across a diverse range of populations. Patients with more severe apnea and sleepiness seem to benefit the most. [ABSTRACT FROM AUTHOR]

Short-term sleep restriction results in impaired glucose tolerance. To test whether habitually short sleep duration increases the risk of developing diabetes, we studied a cohort of 70,026 women enrolled in the Nurses Health Study, without diabetes at baseline, and who responded to a question about daily sleep duration in 1986. Subjects were followed until 1996 for the diagnosis of diabetes (1,969 cases). Long and short sleep durations were associated with an increased risk of diabetes diagnosis. The relative risks (RRs) for short (slept < or =5 h per day) and long (slept > or =9 h per day) sleepers were 1.57 (95% CI 1.28-1.92) and 1.47 (1.19-1.80), respectively. After adjustment for BMI and a variety of confounders, the RR was not significantly increased for short sleepers (1.18 [0.96-1.44]) but remained modestly increased for long sleepers (1.29 [1.05-1.59]). We then performed a similar analysis using only symptomatic cases (n = 1,187). Adjusted RRs for symptomatic diabetes were modestly elevated in both short (1.34 [1.04-1.72]) and long (1.35 [1.04-1.75]) sleepers. Our data suggest that the association between a reduced self-reported sleep duration and diabetes diagnosis could be due to confounding by BMI, or sleep restriction may mediate its effects on diabetes through weight gain. Sleep restriction may be an independent risk factor for developing symptomatic diabetes. [ABSTRACT FROM AUTHOR]

Background: Long-term sleep deprivation is common in today's society. Recent experiments have demonstrated that short-term sleep deprivation in healthy subjects results in adverse physiologic changes, including a decreased glucose tolerance and an increased blood pressure. However, the long-term health consequences of long-term sleep deprivation are unclear. The objective of this study was to determine whether decreased sleep duration (from self-reports) is associated with an increased risk of coronary events. Methods: We studied a cohort of 71 617 US female health professionals (aged 45-65 years), without reported coronary heart disease (CHD) at baseline, who were enrolled in the Nurses' Health Study. Subjects were mailed a questionnaire in 1986 asking about daily sleep duration. Subjects were followed up until June 30, 1996, for the occurrence of CHD-related events. We assessed the relationship between self-reported sleep duration and incident CHD. Results: A total of 934 coronary events were documented (271 fatal and 663 nonfatal) during the 10 years of follow up. Age-adjusted relative risks (95% confidence intervals) of CHD (with 8 hours of daily sleep being considered the reference group) for individuals reporting 5 or fewer, 6, and 7 hours of sleep were 1.82 (1.34-2.41), 1.30 (1.08-1.57), and 1.06 (0.89-1.26), respectively. The relative risk (95% confidence interval) for 9 or more hours of sleep was 1.57 (1.18-2.11). After adjusting for various potential confounders, including snoring, body mass index, and smoking, the relative risks of CHD (95% confidence intervals) for individuals reporting 5 or fewer, 6, and 7 hours of sleep were 1.45 (1.10-1.92), 1.18 (0.98-1.42), and 1.09 (0.91-1.30), respectively. The relative risk (95% confidence interval) for 9 or more hours of sleep was 1.38 (1.03-1.86). Conclusion: Short and long self-reported sleep durations are independently associated with a modestly increased risk of coronary events. [ABSTRACT FROM AUTHOR]

Discusses obstructive sleep apnea. Neurocognitive and cardiovascular sequalae of the disease; Role of anatomical abnormalities in the disease; Diagnosis of the disease; Associations of hypoxemia, hypercapnia and catecholamine with the disorder; Treatments for the disorder. INSET: Search strategy and selection criteria.

Examines the application of the ligand repulsive energy, a steric parameters for ligands, in organometallic systems. Calculation and application of the ligand repulsive energy methodology; Distinction between steric sizes and standard steric measures; Relationship between ligand repulsive energies and model-based steric measurements.

Presents a molecular mechanics model for the eta2 coordination of olefins to metal centers. Calculation of the steric sizes for olefins; Ligand repulsive methodology.

The introduces a continuing medical education (CME) video on the the role of noninvasive ventilation in the management and mitigation of severe, hypercapnic chronic obstructive pulmonary disease (COPD).

This pilot trial aimed to provide evidence for whether the integration of a wearable device with digital behavioral therapy for insomnia (dBTi) improves treatment outcomes and engagement. One hundred and twenty-eight participants with insomnia symptoms were randomized to a 3-week dBTi program (SleepFix®) with a wearable device enabling sleep data synchronization (dBTi+wearable group; n = 62) or dBTi alone (n = 66). Participants completed the Insomnia Severity Index (ISI) and modified Pittsburgh Sleep Quality Index (PSQI) parameters: wake-after-sleep-onset (WASO), sleep-onset-latency (SOL), and total sleep time (TST) at baseline and weeks 1, 2, 3, and primary endpoint of week 6 and follow-up at 12 weeks. Engagement was measured by the number of daily sleep diaries logged in the app. There was no difference in ISI change scores between the groups from pre- to post-treatment (Cohen's d= 0.7, p=.061). The dBTi+wearable group showed greater improvements in WASO (d= 0.8, p =.005) and TST (d= 0.3, p=.049) compared to the dBTi group. Significantly greater engagement (sleep diary entries) was observed in the dBTi+wearable group (mean = 22.4, SD = 10.0) compared to the dBTi group (mean = 14.1, SD = 14.2) (p =.010). This pilot trial found that integration of wearable device with a digital insomnia therapy enhanced user engagement and led to improvements in sleep parameters compared to dBTi alone. These findings suggest that adjunctive wearable technologies may improve digital insomnia therapy effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: Head rotation is thought to have an effect on obstructive sleep apnea (OSA) severity. However, keeping the head rotated fully during sleep is difficult to maintain, and the effect of head rotation is not the same in all OSA patients. Thus, this study aimed to identify whether less head rotation has an effect on airway patency and determine the responder characteristics to the head rotation maneuver (HRM). Methods: We recruited 221 patients who underwent overnight polysomnography and drug-induced sleep endoscopy (DISE) in a tertiary hospital from June 2019 to July 2020. Airway patency and the site of airway collapse were determined in the supine position with the head at 0, 30, and 60 degrees of rotation (HRM0°, HRM30°, and HRM60°, respectively) during DISE. The site of collapse was determined using the VOTE classification system: the velum (palate), oropharyngeal lateral walls, tongue base, and epiglottis. Each structure was labeled as 0, 1, or 2 (patent, partially obstructed, and completely obstructed, respectively). Airway response to the HRM30° and 60° and the clinical characteristics associated with airway opening were analyzed. Results: The study population had a median age of 52 (25–61) years, a body mass index of 26.7(24.6–29.4) kg/m2, and the apnea-hypopnea index (AHI) of 28.2(13.7–71.9) events/h. HRM influenced airway patency positively not only with HRM60° (p<0.001) but also following limited rotation (HRM30°, p<0.001). Patients with tongue base (40.0% with HRM 60°) and epiglottic (52.6% with HRM 60°) collapse responded particularly well to HRM. Multivariate analysis revealed that lower AHI (p<0.001) and an absence of oropharyngeal lateral walls collapse (p = 0.011) were significant predictors of responders to HRM. Conclusion: Head rotation improved airway obstruction in OSA patients, even with a small degree of rotation, and should be further explored as a potential form of therapy in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Editorial. Contends that although sleep disorders are extremely common after a serious stressful or traumatic event, patients probably require therapy if the problem is severe enough for them to seek medical help. Research done by Lavie in this issue; The short-term use of hypnotic agents; View that patients with persistent insomnia should be referred to appropriate specialists.

Background and objective: Animal studies indicate that alpha‐1 adrenergic receptor agonists and antimuscarinic agents improve genioglossus muscle activity during sleep and may be candidates for the pharmacological treatment of OSA. On the other hand, noradrenergic stimulants may be wake‐promoting or cause insomnia symptoms if taken before bedtime, and the addition of a medication with sedative properties, such as an antihistaminic, may reduce these side effects. In this study, we aimed to determine the effects of the combination of an alpha‐1 adrenergic agonist (pseudoephedrine) and an antihistaminic‐antimuscarinic (diphenhydramine) on OSA severity (AHI), genioglossus responsiveness and other endotypic traits (Vpassive, muscle compensation, LG and arousal threshold). Methods: Ten OSA patients performed a randomized, placebo‐controlled, double‐blind, crossover trial comparing one night of pseudoephedrine 120 mg plus diphenhydramine 50 mg (DAW1033D) to placebo administered prior to sleep. The AHI, genioglossus muscle responsiveness to negative oesophageal pressure and the endotypic traits were measured via PSG. Results: The participants' median (interquartile range) age was 50 (46–53) years and body mass index (BMI) was 34.3 (30.6–39.2) kg/m2. The drug combination had no effect on AHI (21.6 (9.1–49.8) on placebo vs 37.9 (5.1–55.4) events/h on DAW1033D, P > 0.5) or genioglossus responsiveness (6.0 (2.6–9.2) on placebo vs 4.0 (3.5–7.3) %/cm H2O). Amongst the phenotypic traits, only Vpassive was improved by 29 (3–55) % eupnoea, P = 0.03 (mean (95% CI)). Conclusion: The combination of pseudoephedrine and diphenhydramine did not improve OSA severity or genioglossus responsiveness but induced a small improvement in upper airway collapsibility, possibly due to the decongestant effect of the medications. The results of this study do not support the use of these medications for OSA treatment. [ABSTRACT FROM AUTHOR]

Background: Conventional metrics to evaluate sleep-disordered breathing (SDB) have many limitations, including their inability to identify subclinical markers of cardiovascular (CV) dysfunction.Research Question: Does sleep study-derived circulation time (Ct) predict mortality, independent of CV risks and SDB severity?Study Design and Methods: We derived average lung to finger Ct (LFCt) from sleep studies in older men enrolled in the multicenter Osteoporotic Fractures in Men (MrOS) Sleep study. LFCt was defined as the average time between end of scored respiratory events and nadir oxygen desaturations associated with those events. We calculated the hazard ratio (HRs) for the CV and all-cause mortality by LFCt quartiles, adjusting for the demographic characteristics, body habitus, baseline CV risk, and CV disease (CVD). Additional models included apnea-hypopnea index (AHI), time with oxygen saturation as measured by pulse oximetry (SpO2) < 90% (T90), and hypoxic burden. We also repeated analyses after excluding those with CVD at baseline.Results: A total of 2,631 men (mean ± SD age, 76.4 ± 5.5 years) were included in this study. LFCt median (interquartile range) was 18 (15-22) s. During an average ± SD follow-up of 9.9 ± 3.5 years, 427 men (16%) and 1,205 men (46%) experienced CV death and all-cause death, respectively. In multivariate analysis, men in the fourth quartile of LFCt (22-52 s) had an HR of 1.36 (95% CI, 1.02-1.81) and 1.35 (95% CI, 1.14-1.60) for CV and all-cause mortality, respectively, when compared with men in the first quartile (4-15 s). The results were similar when additionally adjusting for AHI, T90, or hypoxic burden. Results were stronger among men with no history of CVD at baseline.Interpretation: LFCt is associated with both CV and all-cause mortality in older men, independent of baseline CV burden and SDB metrics. LFCt may be a novel physiologic marker for subclinical CVD and adverse outcomes in patients with SDB. [ABSTRACT FROM AUTHOR]

Exposure to episodic hypoxia induces a persistent augmentation of respiratory activity, known as long-term facilitation (LTF). LTF of phrenic nerve activity has been reported to require serotonin receptor activation and protein syntheses. However, the underlying cellular mechanism still remains poorly understood. NMDA receptors play key roles in synaptic plasticity (e.g. some forms of hippocampal long-term potentiation). The present study was designed to examine the role of NMDA receptors in phrenic LTF and test if the relevant receptors are located in the phrenic motonucleus. Integrated phrenic nerve activity was measured in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats before, during and after three episodes of 5 min isocapnic hypoxia ( Pa,O2= 30–45 mmHg), separated by 5 min hyperoxia (50% O2). Either saline (as control) or the NMDA receptor antagonist MK-801 (0.2 mg kg−1, i.p.) was systemically injected ∼1 h before hypoxia. Phrenic LTF was eliminated by the MK-801 injection (vehicle, 32.8 ± 3.7% above baseline in phrenic amplitude at 60 min post-hypoxia; MK-801, −0.5 ± 4.1%, means ± s.e.m.), with little change in both the CO2-apnoeic threshold and the hypoxic phrenic response (HPR). Vehicle (saline, 5 × 100 nl) or MK-801 (10 μ m; 5 × 100 nl) was also microinjected into the phrenic motonucleus region in other groups. Phrenic LTF was eliminated by the MK-801 microinjection (vehicle, 34.2 ± 3.4%; MK-801, −2.5 ± 2.8%), with minimal change in HPR. Collectively, these results suggest that the activation of NMDA receptors in the phrenic motonucleus is required for the episodic hypoxia-induced phrenic LTF. [ABSTRACT FROM AUTHOR]

Pharyngeal dilator muscles are important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously shown that during wakefulness, the activity of both the genioglossus (GGEMG) and tensor palatini (TPEMG) is greater in patients with OSA compared with controls. Further, EMG activity decreases at sleep onset, and the decrement is greater in apnoea patients than in healthy controls. In addition, it is known that the prevalence of OSA is greater in middle-aged compared with younger men. Thus, we had two goals in this study. First we compared upper airway muscle activity between young and middle-aged healthy men compared with men with OSA. We also explored the mechanisms responsible for the decrement in muscle activity at sleep onset in these groups. We investigated muscle activity, ventilation, and upper airway resistance (UAR) during wakefulness and sleep onset (transition fromα toθ EEG activity) in all three groups. Measurements were obtained during basal breathing (BB) and nasal continuous positive airway pressure (CPAP) was applied to reduce negative pressure-mediated muscle activation). We found that during wakefulness there was a gradation of GGEMG and UAR (younger

Episodic vagus nerve stimulation (VNS) induces phrenic long-term facilitation (LTF, a persistent augmentation of phrenic nerve activity after the stimulation ends), sensitive to the serotonin 5-HT1,2,5,6,7 receptor antagonist methysergide and similar to that elicited by episodic hypoxia or carotid sinus nerve stimulation. This study examined the effect of ketanserin (5-HT2 antagonist) or clozapine (5-HT2,6,7 antagonist) on VNS-induced LTF in anesthetized, vagotomized, paralyzed and ventilated rats to determine which receptor subtype(s) is involved. Three episodes of 5 min VNS (50 Hz, 0.1 ms, ∼500 μA) with 5 min intervals elicited phrenic LTF in control (amplitude: 38% above baseline at 60 min post-VNS) and ketanserin (2 mg·kg-1, i.p.) pre-treated rats (45%), but not clozapine (3 mg·kg-1) rats (8%). These data suggest that unlike hypoxia-induced LTF (5-HT2 receptor-dependent), VNS-induced LTF requires non-5-HT2 serotonin receptors, perhaps 5-HT6 and/or 5-HT7 subtype(s). [Copyright &y& Elsevier]

Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats. Respiratory long-term facilitation (LTF), a serotonin-dependent, persistent augmentation of respiratory activity after episodic hypoxia, is enhanced by pretreatment of chronic intermittent hypoxia (CIH; 5 min 11–12% O2-5 min air, 12 h/night for 7 nights). The present study examined the effects of methysergide (serotonin 5-HT1,2,5,6,7 receptor antagonist), ketanserin (5-HT2 antagonist), or clozapine (5-HT2,6,7 antagonist) on both ventilatory LTF and the CIH effect on ventilatory LTF in conscious male adult rats to determine which specific receptor subtype(s) is involved. In untreated rats (i.e., animals not exposed to CIH), LTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O2) separated by 5-min normoxic intervals, was measured twice by plethysmography. Thus the measurement was conducted 1–2 days before (as control) and ∼1 h after systemic injection of methysergide (1 mg/kg ip), ketanserin (1 mg/kg), or clozapine (1.5 mg/kg). Resting ventilation, metabolic rate, and hypoxic ventilatory response (HVR) were unchanged, but LTF (∼18% above baseline) was eliminated by each drug. In CIH-treated rats, LTF was also measured twice, before and ∼8 h after CIH. Vehicle, methysergide, ketanserin, or clozapine was injected ∼1 h before the second measurement. Neither resting ventilation nor metabolic rate was changed after CIH and/or any drug. HVR was unchanged after methysergide and ketanserin but reduced in four of seven clozapine rats. The CIH-enhanced LTF (∼28%) was abolished by methysergide and clozapine but only attenuated by ketanserin (to ∼10%). Collectively, these data suggest that ventilatory LTF requires 5-HT2 receptors and that the CIH effect on LTF requires non-5-HT2 serotonin receptors, probably 5-HT6 and/or 5-HT7 subtype(s). [ABSTRACT FROM AUTHOR]

In order to compare clinical services in sleep medicine in Japan and the USA, a survey was sent to sleep clinicians who were identified through the American Academy of Sleep Medicine (USA), the Japanese Society of Sleep Research (Japan), and other related sources (Japan). The survey assessed the number of available beds for polysomnography (PSG), the number of overnight PSGs and multiple sleep latency tests (MSLTs) performed, the percentage of PSGs used for diagnosing and evaluating sleep-disordered breathing (SDB) patients, and the main treatment strategies for SDB. The number of beds in sleep centers/laboratories in the USA ranged from two to 12, and PSGs were performed on a daily basis (median number of PSGs per week: 20). However, 67.8% of Japanese sleep facilities did not have beds exclusively used for PSG, and they did occasional PSGs (median: three per month). Because there are a lot of facilities where they did not have beds for PSGs, PSGs were conducted in rooms that served a different purpose. Multiple sleep latency tests in the USA were performed on a weekly basis (i.e. 1–5/week), but were widely unavailable in Japan. On average, 79.4% of PSGs were used to diagnose or manage SDB in the USA. This was more variable in Japan. Nasal continuous positive airway pressure (nCPAP) was the first choice for therapy of most patients with SDB in the USA, while therapy in Japan depended more on the facilities available. A very small number of Japanese sleep facilities are used to conduct PSGs routinely, and fewer still are used for MSLTs. Therefore, most patients remain undiagnosed and untreated. In addition, in Japan, there is no regulatory consensus about the standards of sleep clinics and laboratories, or the requirements for diagnostic methodology or treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a leading cause of morbidity and mortality and although it is linked to sleep apnea, which physiological stressors most strongly associate with incident disease is unclear. We tested whether sleep apnea-specific hypoxic burden (SASHB) predicts incident HF in two independent cohort studies.Research Question: In comparison with apnea-hypopnea index (AHI), how does sleep apnea-specific hypoxic burden predict incident HF?Study Design and Methods: The samples were derived from two cohort studies: The Sleep Heart Health Study (SHHS), which included 4,881 middle-aged and older adults (54.4% women), age 63.6 ± 11.1 years; and the Outcomes of Sleep Disorders in Older Men (MrOS), which included 2,653 men, age 76.2 ± 5.4 years. We computed SASHB as the sleep apnea-specific area under the desaturation curve from pre-event baseline. We used Cox models for incident HF to estimate the adjusted hazard ratios (HRs) for natural log-transformed SASHB and AHI adjusting for multiple confounders.Results: The SASHB predicted incident HF in men in both cohorts, whereas AHI did not. Men in SHHS and MrOS had adjusted HRs (per 1SD increase in SASHB) of 1.18 (95% CI, 1.02-1.37) and 1.22 (95% CI, 1.02-1.45), respectively. Associations with SASHB were observed in men with both low and high AHI levels. Associations were not significant in women.Interpretation: In men, the hypoxic burden of sleep apnea was associated with incident HF after accounting for demographic factors, smoking, and co-morbidities. The findings Suggest that quantification of an easily measured index of sleep apnea-related hypoxias may be useful for identifying individuals at risk for heart disease, while also suggesting targets for intervention. [ABSTRACT FROM AUTHOR]

Background: We recently showed that administration of the combination of the noradrenergic drug atomoxetine plus the antimuscarinic oxybutynin (ato-oxy) prior to sleep greatly reduced OSA severity, likely by increasing upper airway dilator muscle activity during sleep. In patients with OSA who performed the ato-oxy trial with an esophageal pressure catheter to estimate ventilatory drive, the effect of the drug combination (n = 17) and of the single drugs (n = 6) was measured on the endotypic traits over a 1-night administration and compared vs placebo. This study also tested if specific traits were predictors of complete response to treatment (reduction in apnea-hypopnea index [AHI] > 50% and < 10 events/h).Methods: The study was a double-blind, randomized, placebo-controlled trial. The arousal threshold, collapsibility (ventilation at eupneic drive [Vpassive]), ventilation at arousal threshold, and loop gain (stability of ventilatory control, LG1), were calculated during spontaneous breathing during sleep. Muscle compensation (upper airway response) was calculated as a function of ventilation at arousal threshold adjusted for Vpassive. Ventilation was expressed as a percentage of the eupneic level of ventilation (%eupnea). Data are presented as mean [95% CI].Results: Compared with placebo, ato-oxy increased Vpassive by 73 [54 to 91]%eupnea (P < .001) and muscle compensation by 29 [8 to 51]%eupnea (P = .012), reduced the arousal threshold by -9 [-14 to -3]% (P = .022) and LG1 by -11 [-22 to 2]% (P = .022). Atomoxetine alone significantly reduced arousal threshold and LG1. Both agents alone improved collapsibility (Vpassive) but not muscle compensation. Patients with lower AHI, higher Vpassive, and higher fraction of hypopneas over total events had a complete response with ato-oxy.Findings: Ato-oxy markedly improved the measures of upper airway collapsibility, increased breathing stability, and slightly reduced the arousal threshold. Patients with relatively lower AHI and less severe upper airway collapsibility had the best chance for OSA resolution with ato-oxy. [ABSTRACT FROM AUTHOR]

Key points: •Some patients with obstructive sleep apnoea (OSA) respond well to oral appliance therapy, whereas others do not for reasons that are unclear.•In the present study, we used gold‐standard measurements to demonstrate that patients with a posteriorly‐located tongue (natural sleep endoscopy) exhibit a preferential improvement in collapsibility (lowered critical closing pressure) with oral appliances.•We also show that patients with both posteriorly‐located tongue and less severe collapsibility (predicted responder phenotype) exhibit greater improvements in severity of obstructive sleep apnoea (i.e. reduction in event frequency by 83%, in contrast to 48% in predicted non‐responders).•The present study suggests that the structure and severity of pharyngeal obstruction determine the phenotype of sleep apnoea patients who benefit maximally from oral appliance efficacy. A major limitation to the administration of oral appliance therapy for obstructive sleep apnoea (OSA) is that therapeutic responses remain unpredictable. In the present study, we tested the hypotheses that oral appliance therapy (i) reduces pharyngeal collapsibility preferentially in patients with posteriorly‐located tongue and (ii) is most efficacious (reduction in apnoea‐hypopnea index; AHI) in patients with a posteriorly‐located tongue and less‐severe baseline pharyngeal collapsibility. Twenty‐five OSA patients underwent upper airway endoscopy during natural sleep to assess tongue position (type I: vallecula entirely visible; type II: vallecula obscured; type III: vallecula and glottis obscured), as well as obstruction as a result of other pharyngeal structures (e.g. epiglottis). Additional sleep studies with and without oral appliance were performed to measure collapsibility (critical closing pressure; Pcrit) and assess treatment efficacy. Overall, oral appliance therapy reduced Pcrit by 3.9 ± 2.4 cmH2O (mean ± SD) and AHI by 69 ± 19%. Therapy lowered Pcrit by an additional 2.7 ± 0.9 cmH2O in patients with posteriorly‐located tongue (types II and III) compared to those without (type I) (P < 0.008). Posteriorly‐located tongue (p = 0.03) and lower collapsibility (p = 0.04) at baseline were significant determinants of (greater‐than‐average) treatment efficacy. Predicted responders (type II and III and Pcrit < 1 cmH2O) exhibited a greater reduction in the AHI (83 ± 9 vs. 48 ± 8% baseline, P < 0.001) and a lower treatment AHI (9 ± 6 vs. 32 ± 15 events h–1, P < 0.001) than predicted non‐responders. The site and severity of pharyngeal collapse combine to determine oral appliance efficacy. Specifically, patients with a posteriorly‐located tongue plus less‐severe collapsibility are the strongest candidates for oral appliance therapy. Key points: •Some patients with obstructive sleep apnoea (OSA) respond well to oral appliance therapy, whereas others do not for reasons that are unclear.•In the present study, we used gold‐standard measurements to demonstrate that patients with a posteriorly‐located tongue (natural sleep endoscopy) exhibit a preferential improvement in collapsibility (lowered critical closing pressure) with oral appliances.•We also show that patients with both posteriorly‐located tongue and less severe collapsibility (predicted responder phenotype) exhibit greater improvements in severity of obstructive sleep apnoea (i.e. reduction in event frequency by 83%, in contrast to 48% in predicted non‐responders).•The present study suggests that the structure and severity of pharyngeal obstruction determine the phenotype of sleep apnoea patients who benefit maximally from oral appliance efficacy. [ABSTRACT FROM AUTHOR]

Highlights • Retropalatal luminal area is smaller than retroglossal area at end-expiration. • Retropalatal airway is more dynamically-compliant than retroglossal airway. • Negative effort dependence is associated with inspiratory retropalatal narrowing. Abstract Objectives We hypothesized that preferential retropalatal as compared to retroglossal collapse in patients with obstructive sleep apnea was due to a narrower retropalatal area and a higher retropalatal compliance. Patients with a greater retropalatal compliance would exhibit a recognizable increase in negative effort dependence (NED). Methods Fourteen patients underwent upper airway endoscopy with simultaneous recordings of airflow and pharyngeal pressure during natural sleep. Airway areas were obtained by manually outlining the lumen. Compliance was calculated by the change of airway area from end-expiration to a pressure swing of −5 cm H 2 O. NED was quantified for each breath as [peak inspiratory flow minus flow at −5 cm H 2 O]/[peak flow] × 100. Results Compared to the retroglossal airway, the retropalatal airway was smaller at end-expiration (p < 0.001), and had greater absolute and relative compliances (p < 0.001). NED was positively associated with retropalatal relative area change (r = 0.47; p < 0.001). Conclusions Retropalatal airway is narrower and more collapsible than retroglossal airway. Retropalatal compliance is reflected in the clinically-available NED value. [ABSTRACT FROM AUTHOR]

Key points: In most patients with obstructive sleep apnoea (OSA), there is a spontaneous resolution of the breathing disorders during slow wave sleep (SWS) for yet unknown reasons related to non‐anatomical factors.Some recently identified forms of neural memory specific of upper airway muscles may play a role in this phenomenon.In the present study, we show for the first time that a form of memory of the genioglossus (tongue) muscle is greatly enhanced during SWS compared to non‐rapid eye movement stage 2 sleep.The present study represents a step forward in understanding the mechanisms responsible for the spontaneous development of stable breathing during SWS in OSA patients and may help the discovery of novel therapeutic strategies for this disease. Several studies have shown that obstructive sleep apnoea (OSA) improves during slow wave sleep (SWS) for reasons that remain unclear. Recent studies have identified forms of neural memory such as short‐term potentiation or after‐discharge that can occur in response to upper airway obstruction. Neural memory may play a role in the development of stable breathing during SWS by increasing upper airway muscles activity in this sleep stage. We hypothesize that the after‐discharge of the genioglossus muscle following upper airway obstruction is enhanced during SWS compared to non‐rapid eye movement stage 2 (N2). During sleep, we performed five‐breath drops in continuous positive airway pressure (CPAP‐drop) to simulate obstructive events and reflexively activate the genioglossus. Immediately afterwards, CPAP was returned to an optimal level. Once the post‐drop ventilation returned to eupnoea, the genioglossus after‐discharge was measured as the time it took for genioglossus activity to return to baseline levels. In total, 171 CPAP‐drops were analysed from a group of 16 healthy subjects and 19 OSA patients. A mixed‐model analysis showed that after‐discharge duration during SWS was 208% (95% confidence interval = 112% to 387%, P = 0.022) greater than during N2 after adjusting for covariates (ventilatory drive, CPAP levels). There was also a non‐significant trend for a –35% reduction in after‐discharge duration following an arousal vs. no‐arousal from sleep (95% confidence interval = –59.5% to 5%, P = 0.08). Genioglossus after‐discharge is two‐fold greater in SWS vs. N2, which could partly explain the breathing stabilization described in OSA patients during this sleep stage. Key points: In most patients with obstructive sleep apnoea (OSA), there is a spontaneous resolution of the breathing disorders during slow wave sleep (SWS) for yet unknown reasons related to non‐anatomical factors.Some recently identified forms of neural memory specific of upper airway muscles may play a role in this phenomenon.In the present study, we show for the first time that a form of memory of the genioglossus (tongue) muscle is greatly enhanced during SWS compared to non‐rapid eye movement stage 2 sleep.The present study represents a step forward in understanding the mechanisms responsible for the spontaneous development of stable breathing during SWS in OSA patients and may help the discovery of novel therapeutic strategies for this disease. [ABSTRACT FROM AUTHOR]

Key points: A hypersensitive ventilatory control system or elevated “loop gain” during sleep is a primary phenotypic trait causing obstructive sleep apnoea (OSA). Despite the multitude of methods available to assess the anatomical contributions to OSA during wakefulness in the clinical setting (e.g. neck circumference, pharyngometry, Mallampati score), it is currently not possible to recognize elevated loop gain in patients in this context. Loop gain during sleep can now be recognized using simplified testing during wakefulness, specifically in the form of a reduced maximal breath‐hold duration, or a larger ventilatory response to voluntary 20‐second breath‐holds. We consider that easy breath‐holding manoeuvres will enable daytime recognition of a high loop gain in OSA for more personalized intervention. Abstract: Increased “loop gain” of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring loop gain in the clinical setting are lacking. Here we test the hypothesis that elevated loop gain during sleep can be recognized using voluntary breath‐hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath‐holding manoeuvres performed during wakefulness. We assessed (1) maximal breath‐hold duration, and (2) the ventilatory response to 20 s breath‐holds. For comparison, gold standard loop gain values were obtained during non‐rapid eye movement (non‐REM) sleep using the ventilatory response to 20 s pulses of hypoxic–hypercapnic gas (6% CO2–14% O2, mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard loop gain measurement during wakefulness and steady‐state loop gain measurement during sleep using CPAP dial‐ups. Higher loop gain during sleep was associated with (1) a shorter maximal breath‐hold duration (r2 = 0.49, P < 0.001), and (2) a larger ventilatory response to 20 s breath‐holds during wakefulness (second breath; r2 = 0.50, P < 0.001); together these factors combine to predict high loop gain (receiver operating characteristic area‐under‐curve: 92%). Gold standard loop gain values were remarkably similar during wake and non‐REM sleep. The results show that elevated loop gain during sleep can be identified using simple breath‐holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment. [ABSTRACT FROM AUTHOR]

Background: OSA results from the collapse of different pharyngeal structures (soft palate, tongue, lateral walls, and epiglottis). The structure involved in collapse has been shown to impact non-CPAP OSA treatment. Different inspiratory airflow shapes are also observed among patients with OSA. We hypothesized that inspiratory flow shape reflects the underlying pharyngeal structure involved in airway collapse.Methods: Subjects with OSA were studied with a pediatric endoscope and simultaneous nasal flow and pharyngeal pressure recordings during natural sleep. The mechanism causing collapse was classified as tongue-related, isolated palatal, lateral walls, or epiglottis. Flow shape was classified according to the degree of negative effort dependence (NED), defined as the percent reduction in inspiratory flow from peak to plateau.Results: Thirty-one subjects with OSA (mean apnea-hypopnea index score ± SD, 54 ± 27 events/h) who were 50 ± 9 years of age were studied. NED was associated with the structure causing collapse (P < .001). Tongue-related obstruction (n = 13) was associated with a small amount of NED (median, 19; interquartile range [IQR], 14%-25%). Moderate NED was found among subjects with isolated palatal collapse (median, 45; IQR, 39%-52%; n = 8) and lateral wall collapse (median, 50; IQR, 44%-64%; n = 8). The epiglottis was associated with severe NED (median, 89; IQR, 78%-91%) and abrupt discontinuities in inspiratory flow (n = 9).Conclusions: Inspiratory flow shape is influenced by the pharyngeal structure causing collapse. Flow shape analysis may be used as a noninvasive tool to help determine the pharyngeal structure causing collapse. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Upper airway collapsibility predicts the response to several non-continuous positive airway pressure ( CPAP) interventions for obstructive sleep apnoea ( OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility. Methods Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit) and ventilation at CPAP level of 0 cmH2O (Vpassive)) were retrospectively analysed from a randomized controlled trial ( n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index ( AHI) plus an AHI<15 events/h on-therapy. Results Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2O vs 8.9 (8.4-10.4) cmH2O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit, P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve ( AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit ( AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive ( AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cm H2O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies. Conclusion Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and eszopiclone) for OSA. [ABSTRACT FROM AUTHOR]

Background: Surgical patients with OSA are at increased risk for perioperative complications. Postoperative supplemental oxygen is commonly used, but it may contribute to respiratory depression in patients with OSA receiving opioids. The objective of the study is to investigate the effect of postoperative supplemental oxygen on arterial oxygen saturation (Sao2), sleep respiratory events, and CO2 level in patients with untreated OSA.Methods: Consented patients with an apnea hypopnea index (AHI) > 5 events per hour on a preoperative polysomnography were randomized (1:1) to oxygen (O2 group) or no oxygen (control group). The O2 group received oxygen at 3 L/min via nasal prongs for three postoperative nights. The primary outcomes were polysomnographic parameters measuring Sao2, sleep respiratory events, and Pco2 measured by transcutaneous CO2 monitor (PtcCO2) on nights 1 through 3. The intention-to-treat and per protocol analysis were completed.Results: There were 123 patients randomized (O2 group: n = 62; control group: n = 61). On night 3, the O2 vs control group had a higher average Sao2 (95.2% ± 3% vs 91.4% ± 4%, respectively; P < .001) and lower oxygen desaturation index (median, 2.3; 25th-75th percentile, 0.2-13.8 vs median, 18.5; 25th-75th percentile, 8.2-45.9 events per hour, respectively; P < .0001). The O2 group had a decreased AHI (median, 8.0; 25th-75th percentile, 2.1-19.9 vs median, 15.6; 25th-75th percentile, 9.5-45.8, respectively; P = .016), hypopnea index (P < .001), and central apnea index (P = .026) and a shortened longest apnea hypopnea duration (P = .002). Although time percentage with PtcCO2 ≥ 55 mm Hg ≥ 10% on postoperative night 1, 2, or 3 was found in 11.4% patients, there was no difference in PtcCO2 between the groups.Conclusions: Postoperative supplemental oxygen was found to improve oxygenation and decrease the AHI without increasing the duration of apnea-hypopnea event or PtcCO2 level. A small number of patients had significant CO2 retention while receiving supplemental oxygen.Trial Registry: ClinicalTrials.gov; No.: NCT01552304; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Key points Changes in the level of inspired oxygen have dramatic effects on the pathophysiology of obstructive sleep apnoea (OSA): hyperoxia reduces the severity of OSA in some but not all patients, whereas hypoxia transforms obstructive events into central events. Given that OSA is likely to result from the interaction of key pathophysiological traits, including a compromised pharyngeal anatomy, inadequate upper airway muscle function, a large ventilatory response to a disturbance in ventilation (high loop gain) and a low arousal threshold, we examined how changes in oxygen levels alter these traits., Our study demonstrates that the beneficial effect of hyperoxia on OSA severity is solely based on its ability to attenuate loop gain, whereas hypoxia increases loop gain and the arousal threshold in addition to improving pharyngeal collapsibility., Such effects help to explain why oxygen therapy may not work in every patient with OSA and explain the disappearance of OSA and the emergence of central events during hypoxic conditions., Abstract Oxygen therapy is known to reduce loop gain (LG) in patients with obstructive sleep apnoea (OSA), yet its effects on the other traits responsible for OSA remain unknown. Therefore, we assessed how hyperoxia and hypoxia alter four physiological traits in OSA patients. Eleven OSA subjects underwent a night of polysomnography during which the physiological traits were measured using multiple 3-min 'drops' from therapeutic continuous positive airway pressure (CPAP) levels. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Pharyngeal collapsibility was quantified as the ventilation at CPAP of 0 cmH2O. Upper airway responsiveness was defined as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was estimated as the level of ventilatory drive associated with arousal. On separate nights, subjects were submitted to hyperoxia ( n = 9; FiO2 ∼0.5) or hypoxia ( n = 10; FiO2 ∼0.15) and the four traits were reassessed. Hyperoxia lowered LG from a median of 3.4 [interquartile range (IQR): 2.6-4.1] to 2.1 (IQR: 1.3-2.5) ( P < 0.01), but did not alter the remaining traits. By contrast, hypoxia increased LG [median: 3.3 (IQR: 2.3-4.0) vs. 6.4 (IQR: 4.5-9.7); P < 0.005]. Hypoxia additionally increased the arousal threshold (mean ± s.d. 10.9 ± 2.1 l min−1 vs. 13.3 ± 4.3 l min−1; P < 0.05) and improved pharyngeal collapsibility (mean ± s.d. 3.4 ± 1.4 l min−1 vs. 4.9 ± 1.3 l min−1; P < 0.05), but did not alter upper airway responsiveness ( P = 0.7). This study demonstrates that the beneficial effect of hyperoxia on the severity of OSA is primarily based on its ability to reduce LG. The effects of hypoxia described above may explain the disappearance of OSA and the emergence of central sleep apnoea in conditions such as high altitude. [ABSTRACT FROM AUTHOR]

The upper airway is often modeled as a Starling resistor, which predicts that flow is independent of inspiratory effort during flow limitation. However, while some obstructive sleep apnea (OSA) patients exhibit flat, Starling resistor-like flow limitation, others demonstrate considerable negative effort dependence (NED), defined as the percent reduction in flow from peak to mid-inspiration. We hypothesized that the variability in NED could be due to differences in phasic pharyngeal muscle activation between individuals. Therefore, we induced topical pharyngeal anesthesia to reduce phasic pharyngeal muscle activation to see if it increased NED. Twelve subjects aged 50±10 years with a BMI of 35±6kg/m² and severe OSA (apnea-hypopnea index=52±28 events/h) were studied. NED and phasic genioglossus muscle activity (EMGGG) of flow limited breaths were determined before and after pharyngeal anesthesia with lidocaine. Pharyngeal anesthesia led to a 33% reduction in EMGGG activity (p<0.001), but NED worsened only by 3.6±5.8% (p=0.056). In conclusion, phasic EMGGG had little effect on NED. This finding suggests that individual differences in phasic EMGGG activation do not likely explain the variability in NED found among OSA patients. [ABSTRACT FROM AUTHOR]

Home-based exacerbation management programs have been proposed as an approach to reducing the clinical and financial burden of COPD. We demonstrate a framework to evaluate such programs in order to guide program design and performance decisions towards optimizing cost and clinical outcomes. This study models the impact of hypothetical exacerbation management programs through probabilistic Markov simulations. Patients were stratified by risk using exacerbation rates from the ECLIPSE study and expert opinion. Three scenarios were modeled, using base, worst and best case parameters to suggest potential telehealth program performance. In these scenarios, acute exacerbations could be detected early, with sensitivity and specificity ranging from 60-90%. Detected acute exacerbations could be diverted to either a sub-acute pathway (12.5-50% probability), thus entirely avoiding hospitalization, or a lower cost pathway through length-of-stay reduction (14-28% reduction). For a cohort of patients without prior hospitalization, the base case telehealth scenario results in a cumulative per-patient lifetime savings of $2.9K over ∼12 years. For a higher risk cohort of patients with a prior admission and 1 to 2 acute exacerbations per year, a cumulative $16K per patient was saved during the remaining ∼3 life-years. Acceptable prices for home-based exacerbation detection testing were highly dependent on patient risk and scenario, but ranged from $290-$1263 per month for the highest risk groups. These results suggest the economic viability of exacerbation management programs and highlight the importance of risk stratification in such programs. The presented model can further be adapted to model specific programs as trial data becomes available. [ABSTRACT FROM AUTHOR]

Abstract: Cardiopulmonary dysfunction and postictal generalized EEG suppression (PGES) are proposed as possible risk factors for the occurrence of SUDEP. The evolution of cardiorespiratory abnormalities with seizures has not been systematically studied for any age-related findings. Additionally, not many studies have looked into the possible effect of age-related brain maturation on PGES. The purpose of this study was to compare these SUDEP risk factors in adults versus children. We prospectively recorded cardiopulmonary abnormalities during seizures using pulse oximetry, EKG, and respiratory inductance plethysmography. Linear and logistic regression models adjusting for multiple seizures in a single patient were used to compare the cardiorespiratory and EEG findings between adults and children. We recorded 101 seizures in 26 children and 55 seizures in 22 adults. Ictal central apnea and bradycardia occurred more often in children than in adults (p=0.02 and p=0.008, respectively), while ictal tachycardia occurred more often in adults (p=0.001) than in children. Postictal generalized EEG suppression of longer duration occurred more often in adults (p=0.003) than in children. Minimum O2 saturation and seizure duration/generalization/lateralization did not significantly differ between adults and children (p>0.1). Children had more frontal lobe seizures, and adults had more temporal lobe seizures recorded (p=0.01). There may be an age-related effect on cardiorespiratory and EEG abnormalities associated with seizures, with higher rates of apnea and bradycardia in children and a much higher prevalence of PGES of longer duration in adults. This may indicate why, despite lower rates of cardiopulmonary dysfunction, adults die more frequently from SUDEP than children. [Copyright &y& Elsevier]

Key points [ABSTRACT FROM AUTHOR]

The article discusses a study about the association of sleep disorder risk with the health, safety and performance of police officers in the U.S. and Canada. Police officers participated in an online and on-site screening survey. The study found that sleep disorders are common among police officers in North America. Sleep disorders were also found to be associated with an increased risk of self-reported safety, health and performance outcomes. Some of sleep disorders screened in the study include obstructive sleep apnea (OSA), insomnia, excessive wake time sleepiness and narcolepsy with cataplexy.

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) >70%], 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< 0.01], 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< 0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not havemarked 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. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the influence of obstructive sleep apnea (OSA) and gender on genioglossus (GG) activity during rapid eye movement (REM) sleep. Researchers employed continuous positive airway pressure (CPAP) to reduce the influences of upper-airway resistance (RUA) and blood gas disturbances on GG activity. It was found that GG activity is minimized in a stepwise manner when RUA and blood gas disturbances are reduced by CPAP.

Sleep fragmentation (SF), a primary feature of obstructive sleep apnoea (OSA), impairs hippocampal long-term potentiation and causes cognitive/attention deficits. However, its influence upon respiratory control has hardly been studied. This study examined the effect of SF on ventilatory long-term facilitation (LTF, a persistent augmentation of respiratory activity after episodic hypoxia) and the hypoxic ventilatory response (HVR), and investigated the role of adenosine A1 receptors in these SF effects in conscious adult male Sprague–Dawley rats. SF, confirmed by sleep architecture recordings, was achieved by periodic, forced locomotion in a rotating drum (30 s rotation/90 s stop for 24 h). LTF, elicited by five episodes of 5 min poikilocapnic hypoxia (10% O2) with 5 min intervals, was measured by plethysmography. Resting ventilation and metabolic rate were unchanged, HVR was reduced (150.6 ± 3.5% versus 110.4 ± 12.3%) and LTF was eliminated (22.6 ± 0.5% versus−0.1 ± 1.3%) shortly after 24 h SF. The SF-induced impairments were SF duration dependent, and completely reversible as HVR (< 24 h) and LTF (< 48 h) returned spontaneously to their pre-SF values. The SF-impaired HVR was improved (130.3 ± 4.2%) and SF-eliminated LTF was restored (19.6 ± 0.9%) by systemic injection of the adenosine A1 receptor antagonist 8-CPT (2.5 mg kg−1) ∼30 min before LTF elicitation. Both HVR and LTF were also similarly impaired by 24 h total sleep deprivation or 24 h repeated cage tapping-induced SF, but not by a 24 h locomotion control protocol for SF. Collectively, these data suggest that: (1) 24 h SF impairs LTF and poikilocapnic HVR; (2) these impairments require A1 receptors; and (3) SF of OSA may exacerbate OSA via impaired ventilatory control mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: We compared the effect of oxygen on the apnea–hypopnea index (AHI) in six obstructive sleep apnea patients with a relatively high loop gain (LG) and six with a low LG. LG is a measure of ventilatory control stability. In the high LG group (unstable ventilatory control system), oxygen reduced the LG from 0.69±0.18 to 0.34±0.04 (p <0.001) and lowered the AHI by 53±33% (p =0.04 compared to the percent reduction in the low LG group). In the low LG group (stable ventilatory control system), oxygen had no effect on LG (0.24±0.04 on room air, 0.29±0.07 on oxygen, p =0.73) and very little effect on AHI (8±27% reduction with oxygen). These data suggest that ventilatory instability is an important mechanism causing obstructive sleep apnea in some patients (those with a relatively high LG), since lowering LG with oxygen in these patients significantly reduces AHI. [Copyright &y& Elsevier]

One postulated mechanism for obstructive sleep apnoea (OSA) is insufficient drive to the upper-airway musculature during sleep, with increased (compensatory) drive during wakefulness. This generates more electromyographic activity in upper airway muscles including genioglossus. To understand drives to upper airway muscles, we recorded single motor unit activity from genioglossus in male groups of control ( n= 7, 7 ± 2 events h−1) and severe OSA ( n= 9, 54 ± 4 events h−1) subjects. One hundred and seventy-eight genioglossus units were recorded using monopolar electrodes. Subjects were awake, supine and breathing through a nasal mask. The distribution of the six types of motor unit activity in genioglossus (Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic and Tonic Other) was identical in both groups. Single unit action potentials in OSA were larger in area (by 34%, P < 0.05) and longer in duration (by 23%, P < 0.05). Inspiratory units were recruited earlier in OSA than control subjects. In control subjects, Inspiratory Tonic units peaked earlier than Inspiratory Phasic units, while in OSA subjects, Inspiratory Tonic and Phasic units peaked simultaneously. Onset frequencies did not differ between groups, but the peak discharge frequency for Inspiratory Phasic units was higher in OSA (22 ± 1 Hz) than control subjects (19 ± 1 Hz, P= 0.003), but conversely, the peak discharge frequency of Inspiratory Tonic units was higher in control subjects (28 ± 1 Hz versus 25 ± 1 Hz, P < 0.05). Increased motor unit action potential area indicates that neurogenic changes have occurred in OSA. In addition, the differences in the timing and firing frequency of the inspiratory classes of genioglossus motor units indicate that the output of the hypoglossal nucleus may have changed. [ABSTRACT FROM AUTHOR]

Background: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA.Methods: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred.Results: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation.Conclusions: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers. [ABSTRACT FROM AUTHOR]

Background: Whether loss of wakefulness itself can influence pharyngeal dilator muscle activity and responsiveness is currently unknown. A study was therefore undertaken to assess the isolated impact of sleep on upper airway muscle activity after minimising respiratory/mechanical inputs.Methods: Ten healthy subjects were studied. Genioglossus (GG), tensor palatini (TP) and diaphragm (DIA) electromyography (EMG), ventilation and sleep-wake status were recorded. Non-invasive positive pressure ventilation was applied. Expiratory pressure was adjusted to yield the lowest GGEMG, thereby minimising airway negative pressure (mechanoreceptor) effects. Inspiratory pressure, respiratory rate and inspiratory time were adjusted until the subjects ceased spontaneous ventilation, thereby minimising central respiratory input. Muscle activity during wakefulness, wake-sleep transitions, stable non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep were evaluated in the supine position.Results: In transitions from wakefulness to sleep, significant decrements were observed in both mean GGEMG and TPEMG (1.6 (0.5)% to 1.3 (0.4)% of maximal GGEMG; 4.3 (2.3)% to 3.7 (2.1)% of maximal TPEMG). Compared with sleep onset, the activity of TP during stable NREM sleep and REM sleep was further decreased (3.7 (2.1)% vs 3.0 (2.0)% vs 3.0 (2.0)% of maximal EMG). However, GGEMG was only further reduced during REM sleep (1.3 (0.4)% vs 1.0 (0.3)% vs 1.1 (0.4)% of maximal EMG).Conclusion: This study suggests that wakefulness per se, independent of respiratory/mechanical stimuli, can influence pharyngeal dilator muscle activity. [ABSTRACT FROM AUTHOR]

Background: Whether loss of wakefulness itself can influence pharyngeal dilator muscle activity and responsiveness is currently unknown. A study was therefore undertaken to assess the isolated impact of sleep on upper airway muscle activity after minimising respiratory/mechanical inputs. Methods: Ten healthy subjects were studied. Genioglossus (GG), tensor palatini (TP) and diaphragm (DIA) electromyography (EMG), ventilation and sleep-wake status were recorded. Non-invasive positive pressure ventilation was applied. Expiratory pressure was adjusted to yield the lowest GGEMG, thereby minimising airway negative pressure (mechanoreceptor) effects. Inspiratory pressure, respiratory rate and inspiratory time were adjusted until the subjects ceased spontaneous ventilation, thereby minimising central respiratory input. Muscle activity during wakefulness, wake-sleep transitions, stable non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep were evaluated in the supine position. Results: In transitions from wakefulness to sleep, significant decrements were observed in both mean GGEMG and TPEMG (1.6 (0.5)% to 1.3 (0.4)% of maximal GGEMG; 4.3 (2.3)% to 3.7 (2.1)% of maximal TPEMG). Compared with sleep onset, the activity of TP during stable NREM sleep and REM sleep was further decreased (3.7 (2.1)% vs 3.0 (2.0)% vs 3.0 (2.0)% of maximal EMG). However, GGEMG was only further reduced during REM sleep (1.3 (0.4)% vs 1.0 (0.3)% vs 1.1 (0.4)% of maximal EMG). Conclusion: This study suggests that wakefulness per se, independent of respiratory/mechanical stimuli, can influence pharyngeal dilator muscle activity. [ABSTRACT FROM AUTHOR]