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Nasim Montazeri Ghahjaverestan,1,2 Cristiano Aguiar,3 Richard Hummel,3 Xiaoshu Cao,4,5 Jackson Yu,3 T Douglas Bradley2,3,5,6 1Sleep and Brain Health Laboratory, Sunnybrook Research Institute, Toronto, Ontario, Canada; 2Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; 3Bresotec Inc, Toronto, Ontario, Canada; 4Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; 5KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada; 6Department of Medicine of the University Health Network, Toronto General Hospital, Toronto, Ontario, CanadaCorrespondence: T Douglas Bradley, University Health Network Toronto General Hospital, Room 9N-943, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada, Tel +416-340-4719, Fax +416-340-4197, Email douglas.bradley@utoronto.caPurpose: 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.Keywords: sleep apnea, portable sleep testing, tracheal acoustics

Nasim Montazeri Ghahjaverestan,1,2 Wei Fan,3 Cristiano Aguiar,3 Jackson Yu,3 T Douglas Bradley1,3– 5 1Sleep Research Laboratory of the University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada; 2Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; 3Bresotec Inc., Toronto, Ontario, Canada; 4Department of Medicine of the University of Toronto, Toronto, Ontario, Canada; 5Department of Medicine of the University Health Network Toronto General Hospital, Toronto, Ontario, CanadaCorrespondence: T Douglas Bradley, Department of Medicine of the University Health Network Toronto General Hospital, Room 9N-943, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada, Tel +1 416-340-4719, Fax +1 416-340-4197, Email douglas.bradley@utoronto.caPurpose: 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.Keywords: respiratory airflow, sleep apnea, tracheal acoustics

Xiaoshu Cao,1,2 Cristina de Oliveira Francisco,2 T Douglas Bradley,2– 4 Nasim Montazeri Ghahjaverestan,1,2 Susan M Tarlo,3,5,6 Matthew B Stanbrook,3,5 Kenneth R Chapman,3,5 Mark Inman,7 Azadeh Yadollahi1,2 1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; 2KITE, Toronto Rehabilitation Institute - University Health Network, Toronto, ON, Canada; 3Department of Medicine, University of Toronto, Toronto, ON, Canada; 4Department of Medicine, University Health Network Toronto General Hospital, Toronto, ON, Canada; 5Department of Medicine, University Health Network Toronto Western Hospital, Toronto, ON, Canada; 6Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 7Faculty of Medicine (Respirology), McMaster University, Hamilton, ON, CanadaCorrespondence: Azadeh Yadollahi, KITE, Toronto Rehabilitation Institute - University Health Network, Room 12-106, 550 University Avenue, Toronto, ON, M5G 2A2, Canada, Email azadeh.yadollahi@uhn.caRationale: 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.Keywords: asthma, obstructive sleep apnea, small airway narrowing, thoracic fluid volume

RATIONALE: Fluid accumulation in the legs and its overnight redistribution into the neck appears to play a causative role in obstructive sleep apnea (OSA) in sedentary men. Chronic venous insufficiency (CVI) promotes fluid accumulation in the legs that can be counteracted by compression stockings. OBJECTIVES: To test the hypotheses that, in nonobese subjects with CVI and OSA, wearing compression stockings during the day will attenuate OSA by reducing the amount of fluid displaced into the neck overnight. METHODS: Nonobese subjects with CVI and OSA were randomly assigned to 1 week of wearing compression stockings or to a 1-week control period without compression stockings, after which they crossed over to the other arm. Polysomnography and measurement of overnight changes in leg fluid volume and neck circumference were performed at baseline and at the end of compression stockings and control periods. MEASUREMENTS AND MAIN RESULTS: Twelve subjects participated. Compared with the end of the control period, at the end of the compression stockings period there was a 62% reduction in the overnight leg fluid volume change (P = 0.001) and a 60% reduction in the overnight neck circumference increase (P = 0.001) in association with a 36% reduction in the number of apneas and hypopneas per hour of sleep (from 48.4 ± 26.9 to 31.3 ± 20.2, P = 0.002). CONCLUSIONS: Redistribution of fluid from the legs into the neck at night contributes to the pathogenesis of OSA in subjects with CVI. Prevention of fluid accumulation in the legs during the day, and its nocturnal displacement into the neck, attenuates OSA in such subjects. [ABSTRACT FROM AUTHOR]

Objective: To test the ability of a microphone recording system, located distal to the respiratory outflow tract, to track the timing of the inspiratory and expiratory phases of breathing in awake healthy subjects.Methods: Fifteen subjects participated. Breath sounds were recorded using a microphone embedded in a face frame in a fixed location in relation to the nostrils and mouth, while simultaneously recording respiratory movements by respiratory inductance plethysmography (RIP). Subjects were studied while supine and were instructed to breathe normally for 2 min: through their noses only (nasal breathing), during the first min, and through their mouths only (oral breathing) during the second min. Five subjects (test group) were chosen randomly to extract features from their acoustic data. Ten breaths (5 nasal and 5 oral breaths) from each subject were studied. Inspiratory and expiratory segments of breath sounds were determined and extracted from the acoustic data by comparing it to the RIP trace. Subsequently, the frequency spectrum of each phase was then determined. Spectral variables derived from the 5 test subjects were applied prospectively to detect breathing phases in the remaining 10 subjects (validation group).Results: Test group data showed that the mean of all inspiratory spectra peaked between 30 and 270 Hz, flattened between 300 and 1,100 Hz, and peaked again with a center frequency of 1,400 Hz. The expiratory spectra peaked between 30 and 180 Hz and its power dropped off exponentially after that. Accordingly, the bands ratio (BR) of frequency magnitudes between 500 and 2500 Hz to frequency magnitudes between 0 and 500 Hz was chosen as a feature to distinguish between breathing phases. BR for the mean inspiratory spectrum was 2.27 and for the mean expiratory spectrum was 0.15. The route of breathing did not affect the BR ratio within the same phase. When this BR was applied to 436 breathing phases in the validation group, 424 (97%) were correctly identified (Kappa = 0.96, P < 0.001) indicating strong agreement between the acoustic method and the RIP.Conclusion: Frequency spectra of breathing sounds recorded from a face-frame, reliably identified the inspiratory and expiratory phases of breathing. This technique may have various applications for respiratory monitoring and analysis. [ABSTRACT FROM AUTHOR]

RATIONALE: The cause of increased pharyngeal collapsibility in patients with obstructive sleep apnea is incompletely understood. In awake healthy subjects, we showed that fluid displacement from the legs into the neck induced by lower body positive pressure reduces upper airway size and increases its collapsibility. Prolonged sitting leads to dependent fluid accumulation in the legs. OBJECTIVES: To test the hypotheses that the apnea-hypopnea index (AHI) during sleep will be related to the amount of fluid spontaneously displaced from the legs overnight, and that this will, in turn, be related to the time spent sitting the previous day. METHODS: In 23 nonobese healthy men referred for sleep studies for suspected obstructive sleep apnea, we assessed the changes in leg fluid volume and in neck circumference from the beginning to the end of the night, and the time spent sitting during the previous day. MEASUREMENTS AND MAIN RESULTS: The overnight change in leg fluid volume correlated strongly with the AHI (r = -0.773, P < 0.001), the change in neck circumference (r = -0.792, P < 0.001), and the time spent sitting (r = -0.588, P = 0.003). Multivariate analysis showed that the only significant independent correlates of the AHI were the overnight changes in leg fluid volume and neck circumference, which together explained 68% of the variability in the AHI among subjects. CONCLUSIONS: These novel findings suggest that overnight rostral fluid displacement from the legs, related to prolonged sitting, may play a previously unrecognized role in the pathogenesis of obstructive sleep apnea in nonobese men that is independent of body weight. [ABSTRACT FROM AUTHOR]

Introduction: Fluid displacement into nuchal and peripharyngeal soft tissues while recumbent may contribute to narrowing and increased airflow resistance of the pharynx (Rph), and predispose to pharyngeal collapse in patients at risk for obstructive sleep apnea. OBJECTIVES: To determine whether displacement of fluid from the lower body to the neck will increase both neck circumference and Rph in healthy subjects. METHODS: In 11 healthy, nonobese subjects, studied while awake and supine, leg fluid volume, neck circumference, and Rph were measured at baseline. Subjects were then randomized to a control period or to application of lower body positive pressure (LBPP) of 40 mm Hg via antishock trousers to displace fluid from the legs, after which they crossed over to the other arm. Baseline measurements were repeated at 1 and 5 min during the control and LBPP periods. RESULTS: Compared with the control period, application of LBPP caused a significant reduction in leg fluid volume (p < 0.001) and a significant increase in neck circumference (p = 0.004). Rph remained stable during the control period, but increased significantly from baseline after 1 and 5 min of LBPP (from 0.43 +/- 0.10 to 0.60 +/- 0.11 cm H(2)O/L/s, p = 0.034, and to 0.87 +/- 0.19 cm H(2)O/L/s, p < 0.001, compared with baseline, respectively). CONCLUSIONS: Fluid displacement from the legs by LBPP increases neck circumference and Rph in healthy subjects. These findings suggest the hypothesis that fluid displacement to the upper body during recumbency may predispose to pharyngeal obstruction during sleep, especially in fluid overload states, such as heart and renal failure. [ABSTRACT FROM AUTHOR]

Obstructive and central sleep apnea are common in heart failure, and may participate in its progression by exposing the heart to intermittent hypoxia, increased preload and afterload, sympathetic activation, and vascular endothelial dysfunction. Treatment of sleep apnea in patients with heart failure may reverse these detrimental effects, in addition to alleviating symptoms of sleep apnea. In patients with heart failure and obstructive sleep apnea, short-term randomized trials have demonstrated that continuous positive airway pressure (CPAP) improves cardiac function, and lowers sympathetic activity and blood pressure. However, there are no data on whether treating obstructive sleep apnea in patients with heart failure improves morbidity and mortality. Various treatments have been tested in heart failure patients with central sleep apnea, particularly oxygen and CPAP. Both reduce the frequency of central respiratory events, and lower sympathetic activity. In addition, CPAP improves cardiac function. However, the largest randomized trial did not demonstrate any beneficial effect of CPAP on the rate of mortality and cardiac transplantation (32 vs. 32 events in the control and treatment groups, respectively; p=0.54), but ultimately lacked power to conclude with certainty whether CPAP has an effect on morbidity and mortality in such patients. Thus, although there are data to indicate that treating both obstructive and central sleep apnea in patients with heart failure improves cardiovascular function, larger randomized trials involving interventions such as oxygen, CPAP, or other forms of positive airway pressure will be required to determine whether treating these sleep-related breathing disorders reduces clinically important outcomes such as morbidity and mortality. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Obstructive sleep apnea is common among patients with heart failure and exposes the left ventricle to trophic mechanical and adrenergic stimuli. We hypothesized that in heart failure patients with nonischemic dilated cardiomyopathy (a condition characterized by eccentric hypertrophy), those with obstructive sleep apnea would have a higher prevalence of left ventricular hypertrophy by wall thickness criteria (> or = 12 mm), and greater septal thickness than those without obstructive sleep apnea. Methods and Results: We performed echocardiography and polysomnography in 47 patients with nonischemic dilated cardiomyopathy. Obstructive sleep apnea was present in 45% of these patients. The prevalence of left ventricular hypertrophy was greater in those with than in those without obstructive sleep apnea (47.6 vs. 15.4%, p = 0.016). Interventricular septal thickness (p < 0.001) and relative wall thickness (p = 0.011) were significantly greater in those with than in those without obstructive sleep apnea. However, there was no significant difference in posterior wall thickness between the groups. The frequency of obstructive apneas and hypopneas during sleep was the only significant independent correlate of septal thickness (p = 0.001). Conclusions: In patients with nonischemic dilated cardiomyopathy, the presence of obstructive sleep apnea is associated with an increased prevalence of left ventricular hypertrophy. The higher relative wall thickness and interventricular septal thickness in patients with obstructive sleep apnea indicate that the left ventricle is relatively less eccentric than in patients without obstructive sleep apnea, and that such remodeling affects mainly the septum. These structural adaptations may reflect unique nocturnal mechanical and adrenergic stimuli associated with obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

Rationale: Sleep-disordered breathing has been linked to stroke in previous studies. However, these studies either used surrogate markers of sleep-disordered breathing or could not, due to cross-sectional design, address the temporal relationship between sleep-disordered breathing and stroke.Objectives: To determine whether sleep-disordered breathing increases the risk for stroke.Methods: We performed cross-sectional and longitudinal analyses on 1,475 and 1,189 subjects, respectively, from the general population. Sleep-disordered breathing was defined by the apnea-hypopnea index (frequency of apneas and hypopneas per hour of sleep) obtained by attended polysomnography. The protocol, including polysomnography, risk factors for stroke, and a history of physician-diagnosed stroke, was repeated at 4-yr intervals.Measurements and Main Results: In the cross-sectional analysis, subjects with an apnea-hypopnea index of 20 or greater had increased odds for stroke (odds ratio, 4.33; 95% confidence interval, 1.32-14.24; p = 0.02) compared with those without sleep-disordered breathing (apnea-hypopnea index, <5) after adjustment for known confounding factors. In the prospective analysis, sleep-disordered breathing with an apnea-hypopnea index of 20 or greater was associated with an increased risk of suffering a first-ever stroke over the next 4 yr (unadjusted odds ratio, 4.31; 95% confidence interval, 1.31-14.15; p = 0.02). However, after adjustment for age, sex, and body mass index, the odds ratio was still elevated, but was no longer significant (3.08; 95% confidence interval, 0.74-12.81; p = 0.12).Conclusions: These data demonstrate a strong association between moderate to severe sleep-disordered breathing and prevalent stroke, independent of confounding factors. They also provide the first prospective evidence that sleep-disordered breathing precedes stroke and may contribute to the development of stroke. [ABSTRACT FROM AUTHOR]

Background: Because patients with chronic heart failure (CHF) can benefit from specific treatment for coexisting obstructive and central sleep apnea (CSA), there is a need to develop accurate screening tools to identify or exclude these sleep-related breathing disturbances (SRBDs) in patients with CHF.Objectives: To evaluate, prospectively, the diagnostic value of nocturnal home oximetry in identifying SRBD in CHF patients and in distinguishing central events from obstructive events.Design: Blinded comparison of hospital and home oximetry, and polysomnographic nocturnal recordingsSetting: Cardiac heart failure and sleep clinics in three tertiary referral centers.Patients: Fifty consecutive patients who were investigated for participation in the Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure with Central Sleep Apnea and were recruited from three different centers.Measurements and results: Patients underwent two oximetry recordings, one at home and one during a polysomnographic study. The criterion for an SRBD was the presence of > 15 apneas and hypopneas per hour of sleep during polysomnography or an oxygen desaturation index of > 10 events per hour during oximetry. The pattern of desaturation/resaturation during oximetry was also examined to distinguish obstructive events from central events. Using a 2% fall in pulse oximetric saturation as the criterion for oxygen desaturation, home oximetry had a 85% sensitivity and a 93% specificity (p < 0.001) for detecting an SRBD. However, the desaturation/resaturation pattern did not accurately distinguish between obstructive events and central events (eg, 100% sensitivity, 17% specificity for identifying CSA). The interpretation of the oximetry recording was highly consistent between scorers (p < 0.001).Conclusions: Overnight home oximetry is a sensitive and specific tool for identifying SRBDs in patients with CHF, but not for distinguishing between obstructive and central events in such patients. [ABSTRACT FROM AUTHOR]

Background: Central sleep apnea (CSA) and Cheyne-Stokes respiration have been reported in association with stroke, but their pathophysiologic correlates have not been well described. Objective: To test the hypotheses that (1) CSA in patients with stroke is associated with nocturnal hypocapnia and (2) in those stroke patients with CSA and with left ventricular (LV) systolic dysfunction, periodic breathing (PB) will have a Cheyne-Stokes respiration pattern in which cycle duration is greater than in those without LV systolic dysfunction. Methods: We prospectively performed polysomnography and echocardiography in 93 patients with stroke. CSA was defined as central apneas and hypopneas occurring at a rate of 10 or more per hour of sleep. In patients with CSA, we compared PB cycle duration between those with normal and impaired LV systolic function (LV ejection fraction [LVEF] > 40% and 40%, respectively). Results: CSA was found in 19% of subjects who had lower nocturnal transcutaneous PCO[2] (39.3 +/- 0.9 vs. 42.8 +/- 0.8 mm Hg, p = 0.015) and a higher prevalence of LVEF of 40% or less (22 vs. 5%, p = 0.043) than stroke patients without CSA. There was no significant difference in stroke location or type between the two groups. In patients with CSA, those with LVEF of 40% or less had a longer PB cycle than those with an LVEF of more than 40% (66.6 +/- 5.6 vs. 46.6 +/- 2.9 seconds, p = 0.006), but had no symptoms of heart failure. Conclusion: In patients with stroke, CSA is associated with hypocapnia and occult LV systolic dysfunction but is not related to the location or type of stroke. The presence of LV systolic dysfunction is associated with a Cheyne-Stokes pattern of hyperpnea. [ABSTRACT FROM AUTHOR]

Aims: To determine cause specific mortality in a cohort of 2266 chemical workers exposed to benzene in various manufacturing processes after 1935.Methods: The cohort has accumulated over 80 000 person-years of observation; about 70% of the workers were followed for more than 30 years since first exposure.Results: Mortality from non-malignant diseases of the blood was increased (SMR 2.17, 95% CI 0.87 to 4.48), and correlated with duration of benzene exposure, although risk had decreased from the previous investigation of this cohort. The risk for leukaemia was slightly above background (SMR 1.14, obs 12, 95% CI 0.59 to 1.99) but has also decreased since the earlier study of this cohort. SMRs for acute non-lymphocytic leukaemia (ANLL), chronic lymphatic leukaemia, and non-Hodgkin's lymphoma were 1.11, 0.42, and 1.06 respectively. There was evidence of a weak trend of increasing SMRs for leukaemia and possibly ANLL with increasing low-level cumulative exposure but not with other measures.Conclusion: Leukaemia and ANLL results were consistent with the mildly increased risk estimates from lower exposure subgroups of the Pliofilm cohort. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether patients with congestive heart failure (CHF) avoid the left lateral decubitus (LLD) position during sleep and, if so, whether this avoidance would be more pronounced in those with greater degrees of cardiomegaly.Background: Anecdotal reports suggest that, in patients with CHF, the LLD position is associated with discomfort due to the enlarged apical heart beat and greater degree of dyspnea (trepopnea) than other positions. It has also been suggested that the LLD position is associated with increased sympathetic nervous activity.Methods: A total of 75 patients with CHF and 75 control subjects underwent nocturnal polysomnography with monitoring of body position. Echocardiography was performed in all patients with CHF to determine left ventricular end-diastolic diameter (LVEDD). A total of 40 patients underwent cardiac catheterization from which pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were obtained.Results: Patients with CHF spent significantly less time in the LLD position than in the right lateral decubitus position. No such difference was observed among control subjects. Among patients with CHF, those with larger LVEDD, higher PCWP, and lower CO spent less time in the LLD position.Conclusions: Patients with CHF avoid the LLD position spontaneously during sleep. This may be a protective strategy to avoid discomfort from the enlarged apical heart beat or further hemodynamic or autonomic compromise. [ABSTRACT FROM AUTHOR]

Sleep disordered breathing (SDB) is considered a risk factor for cardiovascular disease (CVD). Obstructive sleep apnoea (OSA) can be treated with continuous positive airway pressure (CPAP), and central sleep apnoea (CSA), in patients with heart failure with reduced ejection fraction (HFrEF), by peak flow-triggered adaptive servo-ventilation. Presently, there is equipoise as to whether treating SDB prevents cardiovascular events. Some propose treatment for this indication, based on observational data, while others argue against because of the lack of randomised trial evidence. This review evaluates literature concerning the cardiovascular effects of treating SDB with PAP devices in individuals with and without CVDs. Nine observational studies report significantly lower cardiovascular event rates in those treated, than in those not treated, for SDB. Conversely, 12 randomised trials in which excessive daytime sleepiness was generally an exclusion criterion showed no reduction in cardiovascular event rates. The SERVE-HF trial showed an increase in mortality with use of minute ventilation-triggered adaptive servo-ventilation for CSA in patients with HFrEF. In the ADVENT-HF trial, treating HFrEF patients with coexisting OSA or CSA using peak flow-triggered adaptive servo-ventilation was safe and improved sleep structure and heart failure-related quality of life but did not reduce all-cause mortality or cardiovascular events. More evidence is required to determine whether treating CSA in patients with HFrEF prevents cardiovascular events and improves survival. Presently, the rationale for treating SDB with PAP remains improving sleep structure and quality of life, as well as relieving excessive daytime sleepiness, but not reducing cardiovascular events., Competing Interests: Conflict of interest: T.D. Bradley, J.S. Floras and A.G. Logan received research grant support from the Canadian Institutes of Health Research and Philips RS North America. T.D. Bradley reports receiving a speaking honorarium from Philips. J.S. Floras reports receiving a speaking honorarium and travel expenses from Philips., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

The prevalence of obstructive sleep apnea (OSA) is on the rise, driven by various factors including more sensitive diagnostic criteria, increased awareness, enhanced technology through at-home testing enabling easy and cost-effective diagnosis, and a growing incidence of comorbid conditions such as obesity. Treating symptomatic patients with OSA syndrome to enhance quality of life remains a cornerstone approach. However, there is a lack of consensus regarding treatment to improve cardiovascular disease (CVD) outcomes, particularly in light of overall negative results from several randomized controlled trials (RCT) indicating no benefit of positive airway pressure (PAP) therapy on primary and secondary CVD events. These RCTs were limited by suboptimal PAP adherence, use of composite CVD outcomes, and limited diversity and generalizability to Sleep Clinic patients. As such, this workshop assembled clinical experts, as well as researchers in basic and translational science, epidemiology, clinical trials, and population health to discuss the current state, and future research directions to guide personalized therapeutic strategies and future research directions in OSA. There was overall consensus among workshop participants that OSA represents a heterogeneous disease with variable endotypes and phenotypes, and heterogeneous responses to treatment. Future research should prioritize employing multi-modal therapeutic approaches within innovative and adaptive trial designs, focusing on specific subgroups of OSA patients hypothesized to benefit from a CVD perspective. Future work should also be inclusive of diverse populations and consider the life-course of OSA to better comprehend treatment strategies that can address the disproportionate impact of OSA on racially minoritized groups. Further, a more holistic approach to sleep must be adopted to include broader assessments of symptoms, sleep duration, and comorbid sleep and circadian disorders. Finally, it is imperative to establish a sleep research consortium dedicated to collecting raw data and biospecimens categorized by OSA subtypes. This will facilitate mechanistic determinations, foster collaborative research, and help bolster the pipeline of early-career researchers.

When a hollow core fiber is drawn, the core and cladding holes within the internal cane geometry are pressurized with an inert gas to enable precise control over the internal microstructure of the fiber and counteract surface tension forces. Primarily by considering the temperature drop as the fiber passes through the furnace and the geometrical transformation of the internal microstructure from preform-to-fiber, we recently established that the gas pressure within the final 'as-drawn' fiber is substantially below atmospheric pressure. We have also established that slight changes in the gas refractive index within the core and surrounding cladding holes induced by changes in gas pressure are sufficient to significantly affect both the modality and loss of the fiber. Here we demonstrate, through both simulations and experimental measurements, that the combination of these effects leads to transient changes in the fiber's attenuation when the fibers are opened to atmosphere post-fabrication. It is important to account for this phenomenon for accurate fiber characterization, particularly when long lengths of fiber are drawn where it could take many weeks for every part of the internal microstructure to reach atmospheric pressure.

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 (R T ), lower respiratory components (R L ), and upper airway (R UA ) resistances were calculated before and after MMs. Generalized estimation equation method was used to find the predictors of R L among variables including age, sex, body mass index, and the effect of MMs and asthma. Eighteen participants were included. Performing MMs significantly increased R T (2.23 ± 2.08 cmH 2 O/L/s, p = 0.003) and R L (1.52 ± 2.00 cmH 2 O/L/s, p = 0.023) in participants with asthma, while only R L was increased in non-asthma group (1.96 ± 1.73 cmH 2 O/L/s, p = 0.039). We found the model with age, and the effect of MMs and asthma severity generated the highest correlation (R 2  = 0.69, p < 0.001). We provide evidence that fluid accumulation in the thorax caused by excessive intrathoracic pressure increases R L in both non-asthma and asthma groups. The changes in R L were related to age, having asthma and the effect of simulated OSA. This can explain the interrelationship between OSA and asthma., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

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 H 2 O 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 (R 2  = 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 (R 2  = 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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hollow-core optical fibers can offer broadband, single mode guidance in the UV-visible-NIR wavelength range, with the potential for low-loss, solarization-free operation, making them desirable and potentially disruptive for a wide range of applications. To achieve this requires the fabrication of fibers with <300nm anti-resonant membranes, which is technically challenging. Here we investigate the underlying fluid dynamics of the fiber fabrication process and demonstrate a new three-stage fabrication approach, capable of delivering long (∼350m) lengths of fiber with the desired thin-membranes.

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., Competing Interests: Declaration of interests Partial funding for this trial, as well as ASV devices, were provided by Philips RS North America. These resources supported the work of all co-authors and trial sites. TDB reports receiving a speaking honorarium from Philips. JSF reports receiving a speaking honorarium and travel expenses from Philips. MA reports receiving speaking honoraria and research grant support from Philips and ResMed. RJK reports receiving speaking honoraria from Eisa and Powell-Mansfield. JMMT reports receiving speaking honoraria from Gebro, Menarini, and Chiesa and research grant support from GSK and AstraZeneca. All other authors declare no competing interests aside from grant support from Philips RS North America to conduct the clinical trial described herein., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This Letter reports the first, to the best of our knowledge, spectral radiation induced attenuation (RIA) measurements of nested anti-resonant nodeless hollow-core fibers (NANFs). A 5-tube NANF, alongside a solid-core single-mode radiation resistant fiber (SM-RRF), was irradiated under γ-ray up to 101 kGy (SiO 2 ) and under x-ray up to 241 kGy (SiO 2 ). No RIA was observed in the NANF in the second half of the O-band, the S-band, the C-band, and the L-band. The NANF showed a reduction of absorption bands associated with water and HCl under irradiation. Three new attenuation peaks were radiolytically induced and are attributed to the creation of HNO 3 . These peaks are centered respectively at 1441 nm, 1532 nm, and 1628 nm, with a full width at half maximum (FWHM) of, respectively, 10 nm, 12 nm, and 12 nm. These results demonstrate that the wide bandwidth range of NANFs is essentially unaffected by radiation, but the internal gas contents of the NANF must be managed to avoid producing undesirable spectral features through radiolytic reactions. Wide spectral regions almost unaffected by the ionizing radiation could open new possibilities for the use of NANF in harsh radiation environments.

We report simultaneous low coupling loss (below 0.2 dB at 1550 nm) and low back-reflection (below -60 dB in the 1200-1600 nm range) between a hollow core fiber and standard single mode optical fiber obtained through the combination of an angled interface and an anti-reflective coating. We perform experimental optimization of the interface angle to achieve the best combination of performance in terms of the coupling loss and back-reflection suppression. Furthermore, we examine parasitic cross-coupling to the higher-order modes and show that it does not degrade compared to the case of a flat interface, keeping it below -30 dB and below -20 dB for LP 11 and LP 02 modes, respectively.