The Effect of Simulated Obstructive Apneas on Mechanical Characteristics of Lower Airways in Individuals with Asthma.

Increased negative intrathoracic pressure that occurs during pharyngeal obstruction can increase thoracic fluid volume that may contribute to lower airway narrowing in individuals with obstructive sleep apnea (OSA) and asthma. Our previous study showed that fluid accumulation in the thorax induced by simulated OSA can increase total respiratory resistance. However, the effect of fluid shift on lower airway narrowing has not been investigated. To examine the effect of fluid accumulation in the thorax on the resistance of the lower airway. Non-asthma participants and individuals with (un)controlled asthma were recruited and underwent a single-day experiment. A catheter with six pressure sensors was inserted through the nose to continuously measure pressure at different sites of the airway, while a pneumotachograph was attached to a mouthpiece to record airflow. To simulate obstructive apneas, participants performed 25 Mueller maneuvers (MMs) while lying supine. Using the recordings of pressure sensor and airflow, total respiratory (RT), lower respiratory components (RL), and upper airway (RUA) resistances were calculated before and after MMs. Generalized estimation equation method was used to find the predictors of RL among variables including age, sex, body mass index, and the effect of MMs and asthma. Eighteen participants were included. Performing MMs significantly increased RT (2.23 ± 2.08 cmH2O/L/s, p = 0.003) and RL (1.52 ± 2.00 cmH2O/L/s, p = 0.023) in participants with asthma, while only RL was increased in non-asthma group (1.96 ± 1.73 cmH2O/L/s, p = 0.039). We found the model with age, and the effect of MMs and asthma severity generated the highest correlation (R2 = 0.69, p < 0.001). We provide evidence that fluid accumulation in the thorax caused by excessive intrathoracic pressure increases RL in both non-asthma and asthma groups. The changes in RL were related to age, having asthma and the effect of simulated OSA. This can explain the interrelationship between OSA and asthma.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely.

Relationship between airflow limitation in response to upper airway negative pressure during wakefulness and obstructive sleep apnea severity.

PURPOSE: The objective was to determine if alteration in airflow induced by negative pressure (NP) applied to participants' upper airways during wakefulness, is related to obstructive sleep apnea (OSA) severity as determined by the apnea-hypopnea index (AHI). METHODS: Adults 18 years of age or greater were recruited. All participants underwent overnight polysomnography to assess their apnea-hypopnea index (AHI). While awake, participants were twice exposed, orally, to -3 cm H2O of NP for five full breaths. The ratio of the breathing volumes of the last two breaths during NP exposure to the last two breaths prior to NP exposure was deemed the NP ratio (NPR). RESULTS: Eighteen participants were enrolled. A strong relationship between the AHI and the exponentially transformed NPR (ExpNPR) for all participants was observed (R2 = 0.55, p < 0.001). A multivariable model using the independent variable ExpNPR, age, body mass index and sex accounted for 81% of variability in AHI (p = 0.0006). A leave-one-subject-out cross-validation analysis revealed that predicted AHI using the multivariable model, and actual AHI from participants' polysomnograms, were strongly related (R2 = 0.72, p < 0.001). CONCLUSION: We conclude that ExpNPR, was strongly related to the AHI, independently of demographic factors known to be related to the AHI.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial.

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely. FUNDING: Canadian Institutes of Health Research and Philips RS North America.

Sleep Apnea Detection by Tracheal Motion and Sound, and Oximetry via Application of Deep Neural Networks.

Purpose: Sleep apnea (SA) is highly prevalent, but under diagnosed due to inaccessibility of sleep testing. To address this issue, portable devices for home sleep testing have been developed to provide convenience with reasonable accuracy in diagnosing SA. The objective of this study was to test the validity a novel portable sleep apnea testing device, BresoDX1, in SA diagnosis, via recording of trachea-sternal motion, tracheal sound and oximetry. Patients and Methods: Adults with a suspected sleep disorder were recruited to undergo in-laboratory polysomnography (PSG) and a simultaneous BresoDX1 recording. Data from BresoDX1 were collected and features related to breathing sounds, body motions and oximetry were extracted. A deep neural network (DNN) model was trained with 61-second epochs of the extracted features to detect apneas and hypopneas from which an apnea-hypopnea index (AHI) was calculated. The AHI estimated by BresoDX1 (AHIbreso) was compared to the AHI determined from PSG (AHIPSG) and the sensitivity and specificity of SA diagnosis were assessed at an AHIPSG ≥ 15. Results: Two-hundred thirty-three participants (mean ± SD) 50 ± 16 years of age, with BMI of 29.8 ± 6.6 and AHI of 19.5 ± 22.7, were included. There was a strong relationship between AHIbreso and AHIPSG (r = 0.91, p < 0.001). SA detection for an AHIPSG ≥ 15 was highly sensitive (90.0%) and specific (85.9%). Conclusion: We conclude that the DNN model we developed via recording and analyses of trachea-sternal motion and sound along with oximetry provides an accurate estimate of the AHIPSG with high sensitivity and specificity. Therefore, BresoDX1 is a simple, convenient and accurate portable SA monitoring device that could be employed for home SA testing in the future.

Respiratory Motion and Airflow Estimation During Sleep Using Tracheal Movement and Sound.

Purpose: Due to lack of access and high cost of polysomnography, portable sleep apnea testing has been developed to diagnose sleep apnea. Despite being less expensive, and having fewer sensors and reasonable accuracy in identifying sleep apnea, such devices can be less accurate than polysomnography in detecting apneas/hypopneas. To increase the accuracy of apnea/hypopnea detection, an accurate airflow estimation is required. However, current airflow measurement techniques employed in portable devices are inconvenient and subject to displacement during sleep. In this study, algorithms were developed to estimate respiratory motion and airflow using tracheo-sternal motion and tracheal sounds. Patients and Methods: Adults referred for polysomnography were included. Simultaneous to polysomnography, a patch device with an embedded 3-dimensional accelerometer and microphone was affixed to the suprasternal notch to record tracheo-sternal motion and tracheal sounds, respectively. Tracheo-sternal motion was used to train two mathematical models for estimating changes in respiratory motion and airflow compared to simultaneously measured thoracoabdominal motion and nasal pressure from polysomnography. The amplitude of the estimated airflow was then adjusted by the tracheal sound envelope in segments with unstable breathing. Results: Two hundred and fifty-two subjects participated in this study. Overall, the algorithms provided highly accurate estimates of changes in respiratory motion and airflow with mean square errors (MSE) of 3.58 ± 0.82% and 2.82 ± 0.71%, respectively, compared to polysomnographic signals. The estimated motion and airflow from the patch signals detected apneas and hypopneas scored on polysomnography in 63.9% and 88.3% of cases, respectively. Conclusion: This study presents algorithms to accurately estimate changes in respiratory motion and airflow, which provides the ability to detect respiratory events during sleep. Our study suggests that such a simple and convenient method could be used for portable monitoring to detect sleep apnea. Further studies will be required to test this possibility.

Association of Obstructive Apnea with Thoracic Fluid Shift and Small Airways Narrowing in Asthma During Sleep.

Rationale: Obstructive sleep apnea (OSA) is highly prevalent among patients with asthma, suggesting a pathophysiological link between the two, but a mechanism for this has not been identified. Hypothesis: Among patients with asthma, those with OSA will have greater overnight increases in thoracic fluid volume and small airways narrowing than those without OSA. Methods: We enrolled 19 participants with asthma: 9 with OSA (apnea-hypopnea index (AHI) ≥10) and 10 without OSA (AHI <10). All participants underwent overnight polysomnography. Before and after sleep, thoracic fluid volume was measured by bioelectrical impedance and small airways narrowing was primarily assessed by respiratory system reactance at 5Hz using oscillometry. Results: Patients with asthma and OSA (OSA group) had a greater overnight increase in thoracic fluid volume by 120.5 mL than patients without OSA (non-OSA group) (164.4 ± 44.0 vs 43.9 ± 47.3 mL, p=0.006). Compared to the non-OSA group, the OSA group had greater overnight decrease in reactance at 5Hz (-1.08 ± 0.75 vs 0.21 ± 0.27 cmH2O/L/s, p=0.02), and overnight increase in reactance area (14.81 ± 11.09 vs -1.20 ± 2.46 cmH2O/L, p=0.04), frequency dependence of resistance (1.02 ± 0.68 vs 0.05 ± 0.18 cmH2O/L/s, p=0.04), and resonance frequency (2.80 ± 4.14 vs -1.42 ± 2.13 cmH2O/L/s, p=0.04). Conclusion: Patients with asthma and co-existing OSA had greater overnight accumulation of fluid in the thorax in association with greater small airways narrowing than those without OSA. This suggests OSA could contribute to worsening of asthma at night by increasing fluid accumulation in the thorax.

Sleep apnoea and heart failure.

Heart failure and sleep disordered breathing (SDB) are two common conditions that frequently overlap and have been studied extensively in the past three decades. Obstructive sleep apnoea (OSA) may result in myocardial damage due to intermittent hypoxia that leads to increased sympathetic activity and transmural pressures, low-grade vascular inflammation, and oxidative stress. On the other hand, central sleep apnoea and Cheyne-Stokes respiration (CSA-CSR) occurs in heart failure, irrespective of ejection fraction, either reduced (HFrEF), preserved (HFpEF) or mildly reduced (HFmrEF). The pathophysiology of CSA-CSR relies on several mechanisms leading to hyperventilation, breathing cessation and periodic breathing. Pharyngeal collapse may result at least in part from fluid accumulation in the neck, owing to daytime fluid retention and overnight rostral fluid shift from the legs. Although both OSA and CSA-CSR occur in heart failure, the symptoms are less suggestive than in typical (non-heart failure-related) OSA. Overnight monitoring is mandatory for a proper diagnosis, with accurate measurement and scoring of central and obstructive events, since the management will be different depending on whether the sleep apnoea in heart failure is predominantly OSA or CSA-CSR. SDB in heart failure is associated with worse prognosis, including higher mortality, than in patients with heart failure but without SDB. However, there is currently no evidence that treating SDB improves clinically important outcomes in patients with heart failure, such as cardiovascular morbidity and mortality.

Inverse relationship of subjective daytime sleepiness to mortality in heart failure patients with sleep apnoea.

AIMS: Patients with sleep apnoea (SA) and heart failure (HF) are less sleepy than SA patients without HF. HF and SA both increase sympathetic nervous system activity (SNA). SNA can augment alertness. We previously showed that in HF patients, the degree of daytime sleepiness was not related to the severity of SA but was inversely related to SNA. Elevated SNA is associated with increased mortality in HF. Therefore, we hypothesized that in HF patients with SA, the degree of daytime sleepiness will be inversely related to mortality. METHODS AND RESULTS: In a prospective cohort study, 218 consecutive patients with systolic HF had overnight polysomnography. Among them, 80 subjects with SA (apnoea-hypopnoea index ≥15) were followed for a mean of 28 months to determine all-cause mortality rate. Subjective daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). During follow-up, 20 patients died. The 5 year death rate in patients with ESS less than 6 (i.e. less sleepy) was significantly higher than in patients with an ESS at or above the median of 6 (i.e. sleepier) [21.3 deaths/100 patient-years vs. 6.2 deaths/100 patient-years, unadjusted hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.20 to 7.20, P = 0.018]. After adjusting for confounding factors that included sex, history of hypertension, and mean arterial oxyhaemoglobin saturation, compared with the sleepier patients, less sleepy patients had greater risk of mortality (HR 2.56, 95% CI 1.01 to 6.47, P = 0.047). As a continuous variable, ESS scores were inversely related to mortality risk (HR 0.86, 95% CI 0.75 to 0.98, P = 0.022). CONCLUSIONS: In patients with HF and SA, the degree of subjective daytime sleepiness is inversely related to the mortality risk, suggesting that among HF patients with SA, those with the least daytime sleepiness are at greater risk of death. They may therefore have greater potential for mortality benefit from therapy of SA than those with greater daytime sleepiness.

Effect of Ultrafiltration on Sleep Apnea and Cardiac Function in End-Stage Renal Disease.

RATIONALE: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. METHODS: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. -Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no-sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. CONCLUSIONS: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect.

Long-term effects of cardiac rehabilitation on sleep apnea severity in patients with coronary artery disease.

STUDY OBJECTIVES: Sleep apnea (SA) is prevalent among patients with coronary artery disease (CAD) and increases cardiovascular risk. A previous study showed that 1 month of cardiac rehabilitation (CR) reduced severity of SA in patients with CAD by reducing fluid accumulation in the legs during the day and the amount of fluid shifting rostrally into the neck overnight. The aim of this study was to evaluate whether CR will lead to longer-term attenuation of SA in patients with CAD. METHODS: Fifteen patients with CAD and SA who had participated in a 1-month randomized trial of the effects of exercise training on SA were followed up until they completed 6 months of CR (age: 65 ± 10 years; body mass index: 27.0 ± 3.9 kg/m²; apnea-hypopnea index [AHI]: 39.0 ± 16.7). The AHI was evaluated at baseline by polysomnography and then at 6 months by portable monitoring at home. Cardiorespiratory fitness (VO2peak) was evaluated via a graded cardiopulmonary exercise test at baseline and 6 months later. The 6-month CR program included once weekly, 90-minute, in-facility exercise sessions, and 4 days per week at-home exercise sessions. RESULTS: After 6 months of CR, there was a 54% reduction in the AHI (30.5 ± 15.2 to 14.1 ± 7.5, P < .001). Body mass index remained unchanged, but VO2peak increased by 27% (20.0 ± 6.1 to 26.0 ± 8.9 mL/kg/min, P = .04). CONCLUSIONS: Participation in CR is associated with a significant long-term decrease in the severity of SA. This finding suggests that attenuation of SA by exercise could be a mechanism underlying reduced mortality following participation in CR in patients with CAD and SA. CLINICAL TRIAL REGISTRATION: This study is registered at www.controlled-trials.com with identifier number ISRCTN50108373.

Dissociation between objectively quantified snoring and sleep quality.

BACKGROUND: The impact of simple snoring on sleep structure and sleepiness has not been well described. In several studies, self-reported snoring was associated with increased daytime sleepiness. However, most studies did not distinguish patients with simple snoring from those with coexisting obstructive sleep apnea (OSA) using objective measures. We therefore evaluated the relationship between objectively measured snoring and both sleep structure and daytime sleepiness in patients with no or mild OSA. METHODS: Subjects referred for suspected sleep disorders underwent polysomnography (PSG) during which breath sounds were recorded by a microphone. Those with an apnea-hypopnea index (AHI) <15/h were analyzed. Individual snores were identified by a computer algorithm, from which the snore index (SI) was calculated as the number of snores/h of sleep. Sleep stages and arousals were quantified. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) score. RESULTS: 74 (35 males) subjects were included (age, mean ±â€¯SD: 46.4 ±â€¯15.3 years and body mass index: 29.8 ±â€¯7.0 kg/m2). The mean SI was 266 ±â€¯243 snores/h. Subjects were categorized according to their SI into 3 tertiles: SI < 100, between 100-350, and >350. No sleep structure indeces, arousals, or ESS score differed among SI tertiles (p > 0.13). There was no correlation between SI and any of these variables (p > 0.29). In contrast, the AHI was significantly related to frequency of arousals (r = 0.23, p = 0.048). CONCLUSIONS: These findings suggest that simple snoring assessed objectively is not related to indices of sleep structure or subjective sleepiness.

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure.

STUDY OBJECTIVES: In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), stroke volume (SV) falls during hyperpnea of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). We have identified two distinct patterns of hyperpnea: positive, in which end-expiratory lung volume (EELV) remains at or above functional residual capacity (FRC), and negative, in which EELV falls below FRC. The increase in expiratory intrathoracic pressure generated by the latter should have effects on the heart analogous to external chest compression. To test the hypotheses that in HFrEF patients, CSR-CSA with the negative pattern has an auto-resuscitation effect such that compared with the positive pattern, it is associated with a smaller fall in SV and a smaller increase in cardiac workload (product of heart rate and systolic blood pressure). METHODS: In 15 consecutive HFrEF patients with CSR-CSA during polysomnography, hemodynamic data derived from digital photoplethysmography during positive and negative hyperpneas were compared. RESULTS: Compared to the positive, negative hyperpneas were accompanied by reductions in the maximum and mean relative fall in SV of 30% (p = 0.002) and 10% (p = 0.031), respectively, and by reductions in the degree of increases in heart rate and rate pressure product during hyperpnea of 46% (p < 0.001) and 13% (p = 0.007), respectively. CONCLUSIONS: Our findings suggest the novel concept that the negative pattern of CSR-CSA may constitute a form of auto-resuscitation that acts as a compensatory mechanism to maintain SV in patients with severe HF.

Objective Relationship Between Sleep Apnea and Frequency of Snoring Assessed by Machine Learning.

STUDY OBJECTIVES: Snoring is perceived to be directly proportional to sleep apnea severity, especially obstructive sleep apnea (OSA), but this notion has not been thoroughly and objectively evaluated, despite its popularity in clinical practice. This might lead to overdiagnosis or underdiagnosis of OSA. The goal of this study is to examine this notion and objectively quantify the relationship between sleep apnea and snoring detected using advanced signal processing algorithms. METHODS: We studied adults referred for polysomnography, from which the apnea-hypopnea index (AHI) was derived. Breath sounds were recorded simultaneously, from which snoring was accurately quantified using acoustic analysis of breath sounds and machine-learning computer algorithms. The snore index (SI) was calculated as the number of snores per hour of sleep. RESULTS: In 235 patients, the mean AHI was 20.2 ± 18.8 and mean SI was 320.2 ± 266.7 events/h. On the one hand, the overall correlation between SI and AHI was weak but significant (r = .32, P < .0001). There was a significant stepwise increase in SI with increasing OSA severity, but with a remarkable overlap in SI among OSA severity categories. On the other hand, SI had weak negative correlation with central AHI (r = -.14, P = .035). SI had modest positive and negative predictive values for OSA (0.63 and 0.62 on average, respectively) and good sensitivity but low specificity (0.91 and 0.31 on average, respectively) attributed to the large number of snorers without OSA. CONCLUSIONS: Snoring on its own is probably of limited usefulness in assessing sleep apnea presence and severity, because of its weak relationship with AHI. Thus, the complaint of snoring should be interpreted with caution to avoid unnecessary referrals for sleep apnea testing. Conversely, clinicians should be aware of the possibility of missing diagnosis of patients with sleep apnea who have minimal snoring.

Effect of Trendelenburg position and lower-body positive pressure on neck fluid distribution.

Fluid that shifts out of the legs and into the neck when supine can contribute to upper-airway narrowing. The present study investigates the relative contributions of vascular and extravascular fluid to the total accumulation of neck fluid volume (NFV). In 22 healthy awake participants (8 women), aged 42 ± 9 yr, we measured NFV with bioelectrical impedance, internal jugular vein volume (IJVV) with ultrasound, and extravascular NFV (NFVEV) as the difference between NFV and IJVV. Participants were randomly allocated to control and intervention, both of which were conducted on the same day. Measurements were made at baseline and every 5 min thereafter during control and intervention. During intervention, participants received 40 mmHg lower-body positive pressure (LBPP) when supine, followed by LBPP plus 10° Trendelenburg position, then LBPP when supine again, followed by recovery. During control, participants lay supine for equal time. LBPP and LBPP plus Trendelenburg position both increased NFV from baseline compared with control (P < 0.001), with significant contributions from IJVV (P < 0.001). Returning to supine with LBPP, IJVV returned to baseline, but NFV remained elevated because of accumulation of NFVEV. These findings suggest that contributions of IJVV to NFV are immediate but transient, whereas sustained elevation in NFV when supine is likely a result of NFVEV. These findings add new insights into the mechanism by which fluid accumulates in the neck by rostral fluid shift. NEW & NOTEWORTHY This study demonstrates that lying supine for 30 min as well as increased fluid shift out of the legs to simulate nocturnal rostral fluid shift causes fluid to accumulate mainly in the extravascular space of the neck rather than in the internal jugular veins. Therefore, in subjects without fluid-retaining states, extravascular neck fluid accumulation overnight might play a more significant role in the pathophysiology of upper-airway narrowing than intravascular fluid accumulation.

Effects of Increased Pharyngeal Tissue Mass Due to Fluid Accumulation in the Neck on the Acoustic Features of Snoring Sounds in Men.

STUDY OBJECTIVES: Snoring sounds are generated by the vibration of pharyngeal tissue due to the upper airway narrowing. While recorded by a microphone placed over the neck, snoring can pass through the pharyngeal tissue surrounding the upper airway. Thus, changes in the pharyngeal tissue content may change the acoustic properties of the snoring sounds. Rostral fluid shift and the consequent increases in neck fluid volume (NFV) and neck circumference (NC) can increase pharyngeal tissue mass. Therefore, the goal of this study was to investigate the relationship between increases in pharyngeal tissue mass, as assessed by increased NFV and NC, and snoring sounds features. METHODS: We obtained data from a previous study where 20 males who were not obese participated in a daytime polysomnography and their NC and NFV were measured before and after sleep. During sleep, snoring sounds were recorded with a microphone placed over the neck. Spectral centroid of the snoring sounds was estimated. Then, the first five snoring segments were selected from the first and last 30 minutes of stage N2 sleep. RESULTS: We found a significant decrease in the snoring spectral centroid from the beginning to end of sleep. We also found that spectral centroid from the end of sleep in frequency ranges below 200 Hz was inversely correlated with the increases in NFV and NC from before to after sleep. CONCLUSIONS: These results suggest that snoring spectral centroid can be used as a noninvasive and convenient method to assess variations in the pharyngeal tissue mass.

Servo-Ventilation Therapy for Sleep-Disordered Breathing.

As seen in this CME online activity (available at http://journal.cme.chestnet.org/sv-sleep-disorder), central sleep apnea (CSA) is associated with increased mortality in patients with heart failure (HF), and it has been thought that treatment of CSA may improve underlying HF. Positive airway pressure therapy, specifically auto-servoventilation (ASV), can not only suppress abnormal breathing patterns but has been reported to improve cardiac function in HF patients with CSA. In patients with HF and with CSA unsuppressed with CPAP, newer ASV use has been associated with significant CSA improvement; in addition, several studies have reported efficacy of ASV in the treatment of underlying cardiac dysfunction in HF patients with CSA. However, results from the large randomized Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo-Ventilation in Patients with Heart Failure (SERVE-HF) trial (Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. New Engl J Med. 2015;373[12]:1095-1105) showed no significant effect on the primary end point in patients with stable HF with reduced ejection fraction and predominantly CSA, but all-cause and cardiovascular mortality were both increased in the ASV arm. These results are surprising and inconsistent with earlier smaller studies reporting positive surrogate outcomes, and they require additional study and resolution. However, until this is done, there is an urgent educational need for review of the approved labeling and validated clinical use of ASV within the medical community. The purpose of this educational activity is to review the appropriate use of ASV for the treatment of sleep-disordered breathing, including Cheyne-Stokes respiration, treatment-emergent central apnea, and opioid-induced periodic breathing. Emphasis will be placed on proper patient and therapy selection, especially in patients with HF.

Detecting inspiratory flow limitation with temporal features of nasal airflow.

BACKGROUND: Inspiratory flow limitation is a breathing pattern during sleep caused by upper airway (UA) narrowing that occurs during snoring and various degrees of obstructive sleep apnea (OSA). Clinical examination of flow limitation relies on identifying patterns of airflow contour, however this process is subjective and lacks physiological evidence of UA narrowing. Our objective is to derive the temporal features of nasal airflow contour that characterize flow limitation. The features that correlate with UA narrowing can be used to develop machine learning classifiers to detect flow limitation with physiological support. METHODS: Sixteen healthy adult men underwent full daytime polysomnography where the nasal airflow was recorded. Before and after sleep, we measured UA anatomical parameters including neck circumference (NC) and upper-airway cross-sectional area (UA-XSA). We extracted various temporal features of airflow and investigated their relationships with the UA anatomical parameters. RESULTS: We found that three features were correlated with the anatomical parameters associated with UA narrowing: deviation index vs. baseline UA-XSA (r = -0.67, p = 0.01), peak amplitude variability vs. baseline UA-XSA (r = -0.69, p < 0.01), peak amplitude variability vs. ΔNC (r = 0.74, p < 0.01) and peak number vs. baseline UA-XSA (r = -0.54, p = 0.04). CONCLUSIONS: Temporal features of airflow were associated with UA narrowing. Future studies could utilize the features to develop classifiers to detect flow limitation and assess the severity of breathing disorders during sleep in high-risk populations such as pregnant women and children.