Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.

Predicting obstructive sleep apnoea and perioperative respiratory adverse events in children: role of upper airway collapsibility measurements.

BACKGROUND: Obstructive sleep apnoea (OSA) and perioperative respiratory adverse events are significant risks for anaesthesia in children undergoing adenotonsillectomy. Upper airway collapse is a crucial feature of OSA that contributes to respiratory adverse events. A measure of upper airway collapsibility to identify undiagnosed OSA can help guide perioperative management. We investigated the utility of pharyngeal closing pressure (PCLOSE) for predicting OSA and respiratory adverse events. METHODS: Children scheduled for elective adenotonsillectomy underwent in-laboratory polysomnography 2-12 weeks before surgery. PCLOSE measurements were obtained while the child was anaesthetised and breathing spontaneously just before surgery. Logistic regression was used to assess the predictive performance of PCLOSE for detecting OSA and perioperative respiratory adverse events after adjusting for potential covariates. RESULTS: In 52 children (age, mean [standard deviation] 5.7 [1.8] yr; 20 [38%] females), airway collapse during PCLOSE was observed in 42 (81%). Of these, 19 of 42 (45%) patients did not have OSA, 15 (36%) had mild OSA, and eight (19%) had moderate-to-severe OSA. All 10 children with no evidence of airway collapse during the PCLOSE measurements did not have OSA. PCLOSE predicted moderate-to-severe OSA (odds ratio [OR] 1.71; 95% confidence interval [CI]: 1.2-2.8; P=0.011). All children with moderate-to-severe OSA could be identified at a PCLOSE threshold of -4.0 cm H2O (100% sensitivity), and most with no or mild OSA were ruled out (64.7% specificity; receiver operating characteristic/area under the curve=0.857). However, there was no significant association between respiratory adverse events and PCLOSE (OR 1.0; 95% CI: 0.8-1.1; P=0.641). CONCLUSIONS: Measurement of PCLOSE after induction of anaesthesia can reliably identify moderate or severe OSA but not perioperative respiratory adverse events in children before adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ANZCTR ACTRN 12617001503314.

Early life predictors of obstructive sleep apnoea in young adults: Insights from a longitudinal community cohort (Raine study).

OBJECTIVE: Early-life obstructive sleep apnoea (OSA) predictors are unavailable for young adults. This study identifies early-life factors predisposing young adults to OSA. METHODS: This retrospective study included 923 young adults and their mothers from the Western Australian Pregnancy Raine Study Cohort. OSA at 22 years was determined from in-laboratory polysomnography. Logistic regression was used to identify maternal and neonatal factors associated with OSA in young adulthood. RESULTS: OSA was observed in 20.8% (192) participants. Maternal predictors of OSA included gestational diabetes mellitus (odds ratio (OR) 9.54, 95% confidence interval (CI) 1.7, 58.5, P = 0.011), preterm delivery (OR 3.18, 95%CI 1.1,10.5, P = 0.043), preeclampsia (OR 2.95, 95%CI 1.1,8.0, P = 0.034), premature rupture of membranes (OR 2.46, 95%CI 1.2, 5.2, P = 0.015), age ≥35 years (OR 2.28, 95%CI 1.2,4.4, P = 0.011), overweight and obesity (pregnancy BMI≥25 kg/m2) (OR 2.00, 95%CI 1.2,3.2, P = 0.004), pregnancy-induced hypertension (OR 1.89, 95%CI 1.1,3.2, P = 0.019), and Chinese ethnicity (OR 2.36,95%CI 1.01,5.5, P = 0.047). Neonatal predictors included male child (OR 2.10, 95%CI 1.5,3.0, P < 0.0001), presence of meconium-stained liquor during delivery (OR 1.60, 95%CI 1.0,2.5, P = 0.044) and admission to special care nursery (OR 1.51 95%CI 1.0,2.2, P = 0.040). Higher birth lengths reduced OSA odds by 7% for each centimetre (OR 0.93, 95%CI 0.87, 0.99, P = 0.033). CONCLUSIONS: A range of maternal and neonatal factors predict OSA in young adults, including those related to poor maternal metabolic health, high-risk pregnancy and stressful perinatal events. This information could assist in the early identification and management of at-risk individuals and indicates that better maternal health may reduce the likelihood of young adults developing OSA.

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Background: Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. Methods: We developed and validated a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry data from three countries (Australia, the UK, and the USA). The model was validated within-cohort using subject-wise five-fold cross-validation for sleep-wake classification and in a three-class setting for sleep stage classification wake, rapid-eye-movement sleep (REM), non-rapid-eye-movement sleep (NREM) and by external validation. We assessed the face validity of our model for population inference by applying the model to the UK Biobank with 100,000 participants, each of whom wore a wristband for up to seven days. The derived sleep parameters were used in a Cox regression model to study the association of sleep duration and sleep efficiency with all-cause mortality. Findings: After exclusion, 1,448 participant nights of data were used to train the sleep classifier. The difference between polysomnography and the model classifications on the external validation was 34.7 minutes (95% limits of agreement (LoA): -37.8 to 107.2 minutes) for total sleep duration, 2.6 minutes for REM duration (95% LoA: -68.4 to 73.4 minutes) and 32.1 minutes (95% LoA: -54.4 to 118.5 minutes) for NREM duration. The derived sleep architecture estimate in the UK Biobank sample showed good face validity. Among 66,214 UK Biobank participants, 1,642 mortality events were observed. Short sleepers (<6 hours) had a higher risk of mortality compared to participants with normal sleep duration (6 to 7.9 hours), regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.69; 95% confidence intervals (CIs): 1.28 to 2.24 ) or high sleep efficiency (HRs: 1.42; 95% CIs: 1.14 to 1.77). Interpretation: Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.

Shift work, clinically significant sleep disorders and mental health in a representative, cross-sectional sample of young working adults.

Mental health conditions confer considerable global disease burden in young adults, who are also the highest demographic to work shifts, and of whom 20% meet criteria for a sleep disorder. We aimed to establish the relationship between the combined effect of shift work and sleep disorders, and mental health. The Raine Study is the only longitudinal, population-based birth cohort in the world with gold-standard, Level 1 measurement of sleep (polysomnography, PSG) collected in early adulthood. Participants (aged 22y) underwent in-laboratory PSG and completed detailed sleep questionnaires. Multivariable adjusted robust linear regression models were conducted to explore associations with anxiety (GAD7) and depression (PHQ9), adjusted for sex, health comorbidities, and work hours/week. Data were from 660 employed young adults (27.3% shift workers). At least one clinically significant sleep disorder was present in 18% of shift workers (day, evening and night shifts) and 21% of non-shift workers (p = 0.51); 80% were undiagnosed. Scores for anxiety and depression were not different between shift and non-shift workers (p = 0.29 and p = 0.82); but were higher in those with a sleep disorder than those without (Md(IQR) anxiety: 7.0(4.0-10.0) vs 4.0(1.0-6.0)), and depression: (9.0(5.0-13.0) vs 4.0(2.0-6.0)). Considering evening and night shift workers only (i.e. excluding day shift workers) revealed an interaction between shift work and sleep disorder status for anxiety (p = 0.021), but not depression (p = 0.96), with anxiety scores being highest in those shift workers with a sleep disorder (Md(IQR) 8.5(4.0-12.2). We have shown that clinical sleep disorders are common in young workers and are largely undiagnosed. Measures of mental health do not appear be different between shift and non-shift workers. These findings indicate that the identification and treatment of clinical sleep disorders should be prioritised for young workers as these sleep disorders, rather than shift work per se, are associated with poorer mental health. These negative mental health effects appear to be greatest in those who work evening and/or night shift and have a sleep disorder.

Is There a Place for Medicinal Cannabis in Treating Patients with Sleep Disorders? What We Know so Far.

The legalization of cannabis for medicinal, and in some countries, recreational, purposes in addition to growth in the cannabis industry has meant that cannabis use and interest in the area has increased rapidly over the past 20 years. Treatment of poor sleep and sleep disorders are two of the most common reasons for the current use of medicinal cannabis. However, evidence for the role of medical cannabis in the treatment of sleep disorders has not been clearly established, thus making it challenging for clinicians to make evidence-based decisions regarding efficacy and safety. This narrative review summarizes the highest quality clinical evidence currently available in relation to the use of medicinal cannabis for the treatment of sleep disorders including insomnia, obstructive sleep apnea, restless legs syndrome, rapid eye movement sleep behavior disorder, nightmare disorder and narcolepsy. A summary of the effect of cannabis on sleep quality and architecture is also presented. Currently, there is insufficient evidence to support the routine use of medicinal cannabis as an effective and safe treatment option for any sleep disorder. Nevertheless, emerging evidence is promising and warrants further investigation using standardized cannabinoid products and validated quantitative measurement techniques.

Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo.

STUDY OBJECTIVES: This randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the safety and efficacy of 2 weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥3 months). METHODS: Co-primary study endpoints were safety of the medication based on adverse event reporting and global insomnia symptoms (Insomnia Severity Index [ISI]). Secondary endpoints included: self-reported (sleep diary), actigraphy-derived, and polysomnography measurements of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE); and self-reported assessments of sleep quality (sSQ) and feeling rested upon waking. Adjusted mean differences between placebo and ZTL-101 were calculated. RESULTS: Twenty-three of 24 randomized participants (n = 20 female, mean age 53 ± 9 years) completed the protocol. No serious adverse events were reported. Forty mild, nonserious, adverse events were reported (36 during ZTL-101) with all but one resolving overnight or soon after waking. Compared to placebo, ZTL-101 decreased ISI (-5.07 units [95% CI: -7.28 to -2.86]; p = 0.0001) and self-reported SOL (-8.45 min [95% CI: -16.33 to -0.57]; p = 0.04) and increased self-reported TST (64.6 min [95% CI: 41.70 to 87.46]; p < 0.0001), sSQ (0.74 units [95% CI: 0.51 to 0.97]; p < 0.0001), and feeling of being rested on waking (0.51 units [95% CI: 0.24 to 0.78]; p = 0.0007). ZTL-101 also decreased actigraphy-derived WASO (-10.2 min [95% CI: -16.2 to -4.2]; p = 0.002), and increased actigraphy-derived TST (33.4 min [95% CI: 23.07 to 43.76]; p < 0.001) and SE (2.9% [95% CI: 2.0 to 3.8]; p = 0.005). CONCLUSIONS: Two weeks of nightly sublingual administration of a cannabinoid extract (ZTL-101) is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms. CLINICAL TRIAL: ANZCTR; anzctr.org.au; ACTRN12618000078257.

Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep.

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea-hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02-0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, -0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs -2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32-5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs -1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, -0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Upper Airway Collapsibility during Dexmedetomidine and Propofol Sedation in Healthy Volunteers: A Nonblinded Randomized Crossover Study.

BACKGROUND: Dexmedetomidine is a sedative promoted as having minimal impact on ventilatory drive or upper airway muscle activity. However, a trial recently demonstrated impaired ventilatory drive and induction of apneas in sedated volunteers. The present study measured upper airway collapsibility during dexmedetomidine sedation and related it to propofol. METHODS: Twelve volunteers (seven female) entered this nonblinded, randomized crossover study. Upper airway collapsibility (pharyngeal critical pressure) was measured during low and moderate infusion rates of propofol or dexmedetomidine. A bolus dose was followed by low (0.5 µg · kg · h or 42 µg · kg · min) and moderate (1.5 µg · kg · h or 83 µg · kg · min) rates of infusion of dexmedetomidine and propofol, respectively. RESULTS: Complete data sets were obtained from nine volunteers (median age [range], 46 [23 to 66] yr; body mass index, 25.4 [20.3 to 32.4] kg/m). The Bispectral Index score at time of pharyngeal critical pressure measurements was 74 ± 10 and 65 ± 13 (mean difference, 9; 95% CI, 3 to 16; P = 0.011) during low infusion rates versus 57 ± 16 and 39 ± 12 (mean difference, 18; 95% CI, 8 to 28; P = 0.003) during moderate infusion rates of dexmedetomidine and propofol, respectively. A difference in pharyngeal critical pressure during sedation with dexmedetomidine or propofol could not be shown at either the low or moderate infusion rate. Median (interquartile range) pharyngeal critical pressure was -2.0 (less than -15 to 2.3) and 0.9 (less than -15 to 1.5) cm H2O (mean difference, 0.9; 95% CI, -4.7 to 3.1) during low infusion rates (P = 0. 595) versus 0.3 (-9.2 to 1.4) and -0.6 (-7.7 to 1.3) cm H2O (mean difference, 0.0; 95% CI, -2.1 to 2.1; P = 0.980) during moderate infusion of dexmedetomidine and propofol, respectively. A strong linear relationship between pharyngeal critical pressure during dexmedetomidine and propofol sedation was evident at low (r = 0.82; P = 0.007) and moderate (r = 0.90; P < 0.001) infusion rates. CONCLUSIONS: These observations suggest that dexmedetomidine sedation does not inherently protect against upper airway obstruction.

Effects on upper airway collapsibility of presence of a pharyngeal catheter.

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol-anaesthetized subjects (14 men) with and without a multi-sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)-defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow-limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5 ± 5.4 cmH2 O and -2.1 ± 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG-defined OSA (3.9 ± 2.2 cmH2O and 2.6 ± 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 ± 4.9 cmH2O and -3.7 ± 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH2O mL(-1) s(-1) and 16.8 ± 10.1 cmH2O mL(-1) s(-1), P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes.

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

The effect of diaphragm contraction on upper airway collapsibility.

Increasing lung volume increases upper airway patency and decreases airway resistance and collapsibility. The role of diaphragm contraction in producing these changes remains unclear. This study was undertaken to determine the effect of selective diaphragm contraction, induced by phrenic nerve stimulation, on upper airway collapsibility and the extent to which any observed change was attributable to lung volume-related changes in pressure gradients or to diaphragm descent-related mediastinal traction. Continuous bilateral transcutaneous cervical phrenic nerve stimulation (30 Hz) was applied to nine supine, anesthetized human subjects during transient decreases in airway pressure to levels sufficient to produce flow limitation when unstimulated. Stimulation was applied at two intensities (low and high) and its effects on lung volume and airflow quantified relative to unstimulated conditions. Lung volume increased by 386 ± 269 ml (means ± SD) and 761 ± 556 ml during low and high stimulation, respectively (P < 0.05 for the difference between these values), which was associated with peak inspiratory flow increases of 69 ± 57 and 137 ± 108 ml/s, respectively (P < 0.05 for the difference). Stimulation-induced change in lung volume correlated with change in peak flow (r = 0.65, P < 0.01). Diaphragm descent-related outward displacement of the abdominal wall produced no change in airflow unless accompanied by lung volume change. We conclude that phrenic nerve stimulation-induced diaphragm contraction increases lung volume and reduces airway collapsibility in a dose-dependent manner. The effect appears primarily mediated by changes in lung volume rather than mediastinal traction from diaphragm descent. The study provides a rationale for use of continuous phrenic stimulation to treat obstructive sleep apnea.

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND: Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES: To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS: Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN: Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS: HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS: HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION: NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER: NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Feasibility of Applying Real-time Optical Imaging During Bronchoscopic Interventions for Central Airway Obstruction.

BACKGROUND: Interventional bronchoscopists manage central airway obstruction (CAO) through dilation, tumor ablation, and/or stent insertion. Anatomical optical coherence tomography (aOCT), a validated light-based imaging technique, has the unique capacity of providing bronchoscopists with intraprocedural central airway measurements. This study aims to describe the potential role of real-time aOCT in guiding interventions during CAO procedures. METHODS: Prospective case series were recruited from patients referred for bronchoscopic management of symptomatic CAO. Preprocedure chest computed tomography (CT) scans were analyzed for relevant airway dimensions, such as stenosis caliber and length, and aided procedure planning. During bronchoscopy, an aOCT fiberoptic probe was inserted through the working channel of the bronchoscope to image the airway stenosis. From these aOCT images, stenosis dimensions were measured and compared with the preprocedure CT measurements. Preprocedure and postprocedure spirometry, Medical Research Council dyspnea score, and Eastern Cooperative Oncology Group performance status were collected to assess intervention efficacy. RESULTS: Fourteen patients were studied. CT and aOCT-based measurements of airway caliber and length correlated closely (r=0.87, P<0.001). Bland-Altman analysis showed strong agreement between measurements (mean difference 0.4±8.6 mm). The real-time nature of aOCT imaging provided the advantage of more up-to-date measurements where a delay occurred between CT and bronchoscopy or where the quality of the CT image was suboptimal. After bronchoscopy, the predicted forced expiratory flow in 1 second increased from 67±26% to 78±19% (P=0.04). Eastern Cooperative Oncology Group and dyspnea scores improved in 83% and 75% of the patients, respectively. CONCLUSIONS: aOCT provides real-time measurements of obstructing central airway lesions that can assist therapeutic interventions such as selection of endobronchial stents and airway dilatation procedures.

Evolution of changes in upper airway collapsibility during slow induction of anesthesia with propofol.

BACKGROUND: Upper airway collapsibility is known to increase under anesthesia. This study assessed how this increase in collapsibility evolves during slow Propofol induction and how it relates to anesthesia-induced changes in upper airway muscle activity and conscious state. METHODS: Nine healthy volunteers were studied. Anesthesia was induced with Propofol in a step-wise manner (effect-site concentration steps of 0.5 microg x ml(-1) from 0 to 3 microg x ml(-1) and thereafter to 4 microg x ml(-1) and 6 microg x ml(-1) [target-controlled infusion]). Airway patency was maintained with continuous positive airway pressure. Pharyngeal collapsibility was assessed at each concentration by measuring critical pressure. Intramuscular genioglossus electromyogram and anesthetic depth (bispectral index score) were monitored throughout. Loss of consciousness was defined as failure to respond to loud verbal command. RESULTS: Loss of consciousness occurred at varying Propofol effect-site concentrations between 1.5 and 4.0 microg x ml(-1). Initially genioglossus electromyographic activity was sustained with increases in Propofol concentration, increasing in some individuals. At or approaching loss of consciousness, it decreased, often abruptly, to minimal values with an accompanying increase in critical pressure. In most subjects, bispectral index score decreased alinearly with increasing Propofol concentration with greatest rate of change coinciding with loss of consciousness. CONCLUSIONS: Slow stepwise induction of Propofol anesthesia is associated with an alinear increase in upper airway collapsibility. Disproportionate decreases in genioglossus electromyogram activity and increases in pharyngeal critical closing pressure were observed proximate to loss of consciousness, suggesting that particular vulnerability exists after transition from conscious to unconscious sedation. Such changes may have parallels with upper airway behavior at sleep onset.

Effect of body posture on pharyngeal shape and size in adults with and without obstructive sleep apnea.

STUDY OBJECTIVES: In patients with obstructive sleep apnea (OSA), the severity and frequency of respiratory events is increased in the supine body posture compared with the lateral recumbent posture. The mechanism responsible is not clear but may relate to the effect of posture on upper airway shape and size. This study compared the effect of body posture on upper airway shape and size in individuals with OSA with control subjects matched for age, BMI, and gender. PARTICIPANTS: 11 males with OSA and 11 age- and BMI-matched male control subjects. RESULTS: Anatomical optical coherence tomography was used to scan the upper airway of all subjects while awake and breathing quietly, initially when supine, and then in the lateral recumbent posture. A standard head, neck, and tongue position was maintained during scanning. Airway cross-sectional area (CSA) and anteroposterior (A-P) and lateral diameters were obtained in the oropharyngeal and velopharyngeal regions in both postures. A-P to lateral diameter ratios provided an index of regional airway shape. In equivalent postures, the ratio of A-P to lateral diameter in the velopharynx was similar in OSA and control subjects. In both groups, this ratio was significantly less for the supine than for the lateral recumbent posture. CSA was smaller in OSA subjects than in controls but was unaffected by posture. CONCLUSIONS: The upper airway changes from a more transversely oriented elliptical shape when supine to a more circular shape when in the lateral recumbent posture but without altering CSA. Increased circularity decreases propensity to tube collapse and may account for the postural dependency of OSA.