Breathing Events Research Articles

Fetal heart rate responses to maternal sleep-disordered breathing

Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. A total of 84 pregnant women with obesity (body mass index >30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O2 saturation, and O2 saturation variability) were analyzed as potential moderators using linear mixed effects models. A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus.

High prevalence of sleep-disordered breathing in the intensive care unit - a cross-sectional study.

Sleep-disordered breathing may be induced by, exacerbate, or complicate recovery from critical illness. Disordered breathing during sleep, which itself is often fragmented, can go unrecognized in the intensive care unit (ICU). The objectiveof this study was to investigate the prevalence, severity, and risk factors of sleep-disordered breathing in ICU patients using a single respiratory belt and oxygen saturation signals. Patients in three ICUs at Massachusetts General Hospital wore a thoracic respiratory effort belt as part of a clinical trial for up to 7days and nights. Using a previously developed machine learning algorithm, we processed respiratory and oximetry signals to measure the 3% apnea-hypopnea index (AHI) and estimate AH-specific hypoxic burden and periodic breathing. We trained models to predict AHI categories for 12-h segments from risk factors, including admission variables and bio-signals data, available at the start of these segments. Of 129patients, 68% had an AHI ≥ 5; 40% an AHI > 15, and 19% had an AHI > 30 while critically ill. Median [interquartile range] hypoxic burden was 2.8 [0.5, 9.8] at night and 4.2 [1.0, 13.7] %min/h during the day. Of patients with AHI ≥ 5, 26% had periodic breathing. Performance of predicting AHI-categories from risk factors was poor. Sleep-disordered breathing and sleep apnea events while in the ICU are common and are associated with substantial burden of hypoxia and periodic breathing. Detection is feasible using limited bio-signals, such as respiratory effort and SpO2 signals, while risk factors were insufficient to predict AHI severity.

1436-P: Metformin Increases Skeletal Muscle Mitochondrial Function and Acute Phase Insulin Sensitivity in Obstructive Sleep Apnea

Introduction: Obstructive sleep apnea (OSA) is a prevalent sleep disorder with high type 2 diabetes (T2D) risk. OSA therapy includes positive airway pressure (PAP) treatment, which resolves breathing events but modestly improves metabolic health. Metformin is recommended for T2D prevention but is not advocated in patients with OSA. Our pilot study evaluated the effects of metformin on glucose metabolism and mitochondrial function in OSA patients. Methods: Sixteen adults (50.5±1.6 years, BMI: 36.4±0.8 kg/m2) with OSA (apnea hypopnea index: 53.2±21.1 events/hour) were randomized to receive placebo (n=8) or metformin (n=8) treatment along with PAP for 3 months in a double-blind parallel-group design. Whole body and adipose tissue-specific insulin sensitivity (IS) was determined by oral glucose tolerance test (OGTT) . Skeletal muscle mitochondrial function was determined by high-resolution respirometry using biopsies obtained at baseline and after 3 months of treatment. Results: Change in whole body IS (Matsuda index) was not different in metformin or placebo treated groups (p=0.46) . However, improved acute phase responses during OGTT - glucose uptake (p=0.02) , insulin release (p=0.03) , and suppressed lipolysis (p=0.03) were observed with metformin treatment relative to control. Increased skeletal muscle mitochondrial function was evident with metformin relative to control. Specifically, metformin increased complex I phosphorylation and complex IV electron transfer capacity. Conclusion: Metformin treatment improves acute phase IS and insulin suppression of lipolysis in OSA patients. Strikingly, metformin improved skeletal muscle mitochondrial function independent of changes in second phase glucose disposal and BMI, indicating improved tissue metabolic function. These data suggest that in patients with OSA, improvement in tissue level metabolic function may precede changes in whole-body IS and metformin may improve metabolism. Disclosure E.R.M.Zunica: None. E.C.Heintz: None. R.C.Hebert: None. M.C.Tanksley: None. E.C.Mader: None. J.P.Kirwan: None. C.L.Axelrod: None. P.Singh: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK123456789) ;National Institute of General Medical Sciences (GM123456789)

0754 Effects of Atomoxetine plus a Hypnotic on Obstructive Sleep Apnea (OSA) Severity in Patients with a Moderately Collapsible Pharyngeal Airway

Abstract Introduction The combination of atomoxetine and oxybutynin has demonstrated efficacy in the treatment of OSA. Oxybutynin may play a role as an upper airway dilator muscle activator and/or a hypnotic to improve sleep quality. We assessed the effectiveness of atomoxetine when combined with one of two hypnotics. Trazodone is a known hypnotic with possible effects on pharyngeal muscle activity. The other is lemborexant, an orexin antagonist. The effects of both combinations were assessed in patients with OSA and a moderately collapsible pharyngeal airway. Methods Recruited patients were 18 – 65 years of age, with an AHI 4 (4% desaturation criteria) of 10 – 55 and a BMI < 40 kg/m2. Each had to have a moderately collapsible pharyngeal airway using previously defined criteria based on the average percent desaturation during obstructive events (< 8%) and the ratio of hypopneas to total events (> 50%). After a qualifying PSG, each patient spent three nights in the sleep laboratory with approximately one week between studies. Nights were randomized to placebo, atomoxetine 80 mg plus trazodone 100 mg, and atomoxetine 80 mg plus lemborexant 10 mg. Primary outcomes were AHI 4 and the sleep apnea specific hypoxic burden (HB), the area under the SpO2 curve associated with disordered breathing events. Results Fifteen patients completed the trial (median [interquartile range] age was 52 [48-55] and BMI was 33.6 [30 – 35.1] kg/m2. Atomoxetine plus trazodone showed a strong trend for AHI 4 reduction from placebo (from 18.2 [11.8 – 31.3] to 7.4 [5.4 – 16.1] events/h, p=0.064), a significant reduction in HB from placebo (from 48.2 [31.2 – 79.6] to 18.7 [14.9 – 43.5] % min/h) and a trend for a reduction in HB with atomoxetine plus lemborexant (from 34.1 [12.1 – 128.8] to 18.7 [14.9 – 43.5] % min/h, p=0.055). There was no change in total sleep time or arousal index between treatment arms. Mild adverse events were reported on atomoxetine plus trazodone (2/15 sinusitis, 1/15 heartburn). Conclusion In OSA patients with a moderately collapsible upper airway, the combination of atomoxetine plus trazodone yielded clinically meaningful improvements in measures of sleep disordered breathing and oxygenation while atomoxetine plus lemborexant produced smaller effects. Support (If Any) This study was supported by Apnimed.

Accumulation of pathological Ataxin‐7 in the medulla leads to hypoglossal (XII) motor unit pathology

SCA7 is an autosomal dominant neurological disorder caused by a deleterious CAG repeat expansion in the coding region of the ataxin‐7 gene on chromosome 3. Patients with infantile SCA‐7 have the largest repeat expansion characterized by progressive loss of coordination, dysarthria, dysphagia, retinal degeneration and respiratory distress. These infants succumb to death due to severe hypotonia, aspiration pneumonia and respiratory failure. Our objective is to comprehensively analyze the underlying mechanisms that result in upper airway pathology which exacerbates respiratory insufficiency in SCA7. To do this, we will use an infantile SCA7 mouse model: SCA7266Q Knock‐in (KI) mouse. SCA7266Q KI mice exhibit progressive respiratory dysfunction along with irregular breathing and prolonged apneic events with a significant loss of hypoglossal (XII) motoneurons in the medulla. The XII motoneurons innervate the tongue to maintain the shape, stiffness and position of the tongue and regulate the upper airway patency. Therefore, we hypothesize that the expression of pathological ataxin‐7 in the medulla causes XII motor unit pathology leading to upper airway pathology. To confirm if the reduced number of motoneurons resulted in hypoglossal nerve pathology, we analyzed the efferent nerve output of the XII nerve of 9‐week‐old WT control and SCA72666Q KI mice during eupnea and hypercapnia (7% CO2). Later we performed post‐mortem histological analysis of the XII respiratory centers in the medulla and XII nerves. Specifically, we used immunohistochemistry to identify the cells that accumulate ataxin‐7 and we performed TUNEL assay to evaluate the extent of neurodegeneration in the XII motor pool. We analyzed the demyelination of the nerves by light microscopy and electron microscopy. To identify the cellular mechanisms involved in the XII pathology, we performed transcriptome analysis by bulk RNA sequencing of the medulla and confirmed the findings with qPCR.ResultsXII nerve efferent output is blunted at baseline and hypercapnic challenge in SCA7266QKI mice. There is increased TUNEL+ cells in the XII motor pool with intranuclear accumulation of ataxin‐7 in the astrocytes. Further, demyelination is present in the XII nerves in SCA7266QKI mice. RNA sequencing data of the medulla supports these findings and reveals diminished expression of the transcripts regulating the myelination pathway such as Plp1. There is also a significant decrease in activation of astrocytes with attenuated expression of neurotransmitter transporter such as Slc6a9 and Slc710 that are critical for breathing. In conclusion, intranuclear accumulation of ataxin‐7 in SCA7266QKI mice modulates transcription of astrocytes and influences different signaling pathways that result in neurodegeneration, demyelination, and decreased efferent XII nerve output. These findings are clinically relevant and emphasize the importance of neuropathology that results in dysphagia, aspiration pneumonia and respiratory failure in infantile SCA7.

Methods for home-based self-applied polysomnography: the Multicenter AIDS Cohort Study.

Study ObjectivesAlong with multiple chronic comorbidities, sleep disorders are prevalent in people living with human immunodeficiency virus (HIV) infection. The goal of this study was to establish methods for assessing sleep quality and breathing-related disorders using self-applied home polysomnography in people with and without HIV.MethodsSelf-applied polysomnography was conducted on 960 participants in the Multicenter AIDS Cohort Study (MACS) using the Nox A1 recorder to collect data on the frontal electroencephalogram (EEG), bilateral electrooculograms, and a frontalis electromyogram during sleep. Breathing patterns were characterized using respiratory inductance plethysmography bands and pulse oximetry. Continuous recordings of the electrocardiogram were also obtained. All studies were scored centrally for sleep stages and disordered breathing events.ResultsSuccessful home polysomnography was obtained in 807 of 960 participants on the first attempt and 44 participants on the second. Thus, a successful polysomnogram was obtained in 851 (88.6%) of the participants. Reasons for an unsuccessful study included less than 3 h of data on oximetry (34.6%), EEG (28.4%), respiratory inductance plethysmography (21.0%), or two or more of these combined (16.0%). Of the successful studies (N = 851), signal quality was rated as good, very good, or excellent in 810 (95.2%). No temporal trends in study quality were noted. Independent correlates of an unsuccessful study included black race, current smoking, and cocaine use.ConclusionsHome polysomnography was successfully completed in the MACS demonstrating its feasibility in a community cohort. Given the burden of in-lab polysomnography, the methods described herein provide a cost-effective alternative for collecting sleep data in the home.

Changes in airway patency and sleep-breathing in healthy skeletal Class II children undergoing functional activator therapy.

Several studies agree that an abnormal maxilla-mandible relationship correlates better as an Obstructive Sleep Apnea (OSA) predictor, rather than obesity. One of the orthodontic therapies recommended for this kind of craniofacial deformity is to advance the mandible forward with an orthodontic activator, therefore, the aim of this study is to determine if healthy children that use this appliance experience a widening of the upper airway as well as an improvement in their sleep-breathing patterns. 39 healthy children, 20 for activator group (10 boys and 10 girls, 4 mean age 10.9 + 0.9; BMI 16.2 + 1.4), 19 for control group (13 boys and 6 girls, mean age 5 9.8 + 1.4; BMI 17.6 + 2.1) participated in this study. They were required to submit 2 lateral cephalometric radiographs both at initial and final stages of evaluation, and finally three at- home sleep-breathing monitoring results for the activator group and one for the control group. After radiographic evaluation, it was found that children in the activator group experienced an increase in all measured variables. After evaluation with the sleep monitor, an improvement of sleep-breathing was found in children from the activator group (p<0.05). The activator not only provides a harmonious occlusion and proper development of the mandible, but it also helps improve the quality of sleep-breathing through widening of the upper airway and reducing the number of disordered breathing events in children that undergo this therapy.

Simulation of COVID-19 indoor emissions from coughing and breathing with air conditioning and mask protection effects

The COVID-19 infection has emerged as a disruptive pandemic at worldwide level. The study of the mechanism of contagion is one of the greatest challenges before a mass vaccination campaign that would protect populations. The study can support the development of knowledge and tools to develop possible strategies for containing its spread in future events. The saliva droplet aerosol expelled during breathing or coughing is the main cause for the propagation of the SARS-Cov-2. In this work, a URANS CFD approach was used to simulate the dispersion from the mouth of these particles in closed environments. The air conditioning system was considered. The conditions were varied to determine their impact on the diffusion of the aerosol. Lagrangian and Eulerian numerical approaches were used to model the coughing and the breathing events. These were validated with the puff theory, numerical and experimental results. A realistic case of a meeting room with two persons was simulated. Different characteristics of the expulsed aerosols and different ventilation system configurations were considered to demonstrate how these simulations can support management strategies for indoor occupation. Finally, the effect of the protective mask was introduced to quantify its beneficial effects to support safe indoor occupation.

Hypothalamic-Pituitary-Adrenal Activity in Adverse Events Reporting After Placebo Administration.

Participants of clinical trials who receive a placebo treatment often report a variety of adverse events, sometimes called nocebo effects. The reason why these adverse events occur is not clear, and understanding the underlying mechanisms represents a challenge that is likely to improve the interpretation of clinical trials as well as medical practice. Here, we studied 192 healthy subjects who received placebo oxygen through a mask after reading (READ) or not reading (NO-READ) a list of possible adverse events of oxygen breathing: headache, chest pain, abdominal pain, and cough. The whole hypothalamus-pituitary-adrenal axis was assessed just before and right after placebo breathing by measuring the hypothalamic corticotropin-releasing hormone (CRH), pituitary adrenocorticotropic hormone (ACTH), and adrenal cortisol (COR). In addition, both state and trait anxiety were assessed. We found that 64.5% of the NO-READ group reported no adverse events, 30.2% had one, and only 5.2% had two adverse events. In contrast, only 20.8% of the READ group reported no adverse events, whereas 1, 2, 3, and 4 adverse events were reported with a frequency of 21.8%, 19.8%, 19.8%, and 17.7%, respectively. In addition, when the READ group reported three and four adverse events, CRH, ACTH, and COR were significantly increased compared to the NO-READ group, along with an increase in state anxiety scores. These data indicate that hypothalamic-pituitary-adrenal activity and state anxiety are increased in those subjects who report many adverse events after reading a list of adverse events, thus highlighting a possible neuroendocrine mechanism after placebo administration.

Automatic identification of respiratory events based on nasal airflow and respiratory effort of the chest and abdomen

Objective. Disease may cause changes in an individual’s respiratory pattern, which can be measured as parameters for disease evaluation, usually through manually annotated polysomnographic recordings. In this study, a machine learning model based on nasal airflow and respiratory effort of the chest and abdomen is proposed to automatically identify respiratory events, including normal breathing, hypopnea and apnea. Approach. The nasal airflow and chest–abdominal respiratory effort signals were collected by polysomnography (PSG). Time/frequency domain features, fractional Fourier transform features and sample entropy were calculated to obtain feature sets. Features selected through statistical analysis were used as input variables of the machine learning model. The performance of different input combinations on different models was studied and cross-validated. Main results. The dataset included PSG sleep records of 60 patients provided by the Chinese People’s Liberation Army General Hospital. The extreme gradient boosting-based model (XGBoost) performed best in several models with an accuracy of 0.807 and a F1 score of 0.807, depending on the combination of nasal airflow and two respiratory effort signals. The precision for normal breathing, hypopnea and apnea events were 0.764, 0.789 and 0.871, respectively. In addition, the recall scores were 0.833, 0.768 and 0.823 for normal breathing, hypopnea and apnea events, respectively. Moreover, it was found that the standard deviation and kurtosis of nasal airflow were the most important features of the respiratory event detection model. Significance. Since nasal airflow and respiratory effort of the chest and abdomen contain the characteristics of respiratory events, their combined use can improve the classification performance for identification of respiratory events. With this method, respiratory events can be automatically detected and labeled from the PSG records, which can be used to screen for patients with sleep apnea–hypopnea syndrome.

Prematurity, the diagnosis of bronchopulmonary dysplasia, and maturation of ventilatory control.

Infants born before 32 weeks gestational age and receiving respiratory support at 36 weeks postmenstrual age (PMA) are diagnosed with bronchopulmonary dysplasia (BPD). This label suggests that their need for supplemental oxygen (O2 ) is primarily due to acquired dysplasia of airways and airspaces, and that the supplemental O2 is treating residual parenchymal lung disease. However, emerging evidence suggests that immature ventilatory control may also contribute to the need for supplemental O2 at 36 weeks PMA. In all newborns, maturation of ventilatory control continues ex utero and is a plastic process. Among premature infants, supplemental O2 mitigates the hypoxemic effects of delayed maturation of ventilatory control, as well as reduces the duration and frequency of periodic breathing events. Nevertheless, prematurity is associated with altered and occasionally aberrant maturation of ventilatory control. Infants born prematurely, with or without a diagnosis of BPD, are more prone to long-lasting effects of dysfunctional ventilatory control. This review addresses normal and abnormal maturation of ventilatory control and suggests how aberrant maturation complicates assigning the diagnosis of BPD. Greater awareness of the interaction between parenchymal lung disease and delayed maturation of ventilatory control is essential to understanding why a given premature infant requires and is benefitting from supplemental O2 at 36 weeks PMA.

A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers

PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150’s safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21–64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714.

Fast and cost-effective method for non-contact respiration rate tracking using UWB impulse radar

Breathing rate monitoring for a long period provides a valuable indicator about human health and an early warning of possible disasters on the well-being. To gain a comfortable and adequate measurement without restricting the person's privacy, this study investigates a novel non-contact-based solution using ultra wide-band (UWB) impulse radar. We propose a fast and low-cost method for breathing events detection and respiration rate (RR) tracking. This novel approach consists of three main parts: vital signs (VS) patterns extraction based on the Generalized Goertzel Algorithm (GGA) avoiding the prior knowledge of the person's location and overcoming the effect of the clutter. RR tracking built on the complex adaptive notch filter (CANF) with a variable step size to obtain a robust estimation under the presence of sparse random body movement (SRBM) and fast tracking of the breath variability. Finally, we introduce a control chart of the breathing process using the double exponential moving average (DEMA) in order to detect the apnea events. The proposed method is evaluated using two sets of experiments, from mechanical vibrating structure to human subject. The results demonstrate that the proposed system is a promising and effective solution and provides wide usability for continuous monitoring applications. Moreover, it outperforms the state-of-the-art, in terms of computation cost and space complexity.

Estimation of Apnea-Hypopnea Index Using Deep Learning On 3-D Craniofacial Scans.

Obstructive sleep apnea (OSA) is characterized by decreased breathing events that occur through the night, with severity reported as the apnea-hypopnea index (AHI), which is associated with certain craniofacial features. In this study, we used data from 1366 patients collected as part of Stanford Technology Analytics and Genomics in Sleep (STAGES) across 11 US and Canadian sleep clinics and analyzed 3D craniofacial scans with the goal of predicting AHI, as measured using gold standard nocturnal polysomnography (PSG). First, the algorithm detects pre-specified landmarks on mesh objects and aligns scans in 3D space. Subsequently, 2D images and depth maps are generated by rendering and rotating scans by 45-degree increments. Resulting images were stacked as channels and used as input to multi-view convolutional neural networks, which were trained and validated in a supervised manner to predict AHI values derived from PSGs. The proposed model achieved a mean absolute error of 11.38 events/hour, a Pearson correlation coefficient of 0.4, and accuracy for predicting OSA of 67% using 10-fold cross-validation. The model improved further by adding patient demographics and variables from questionnaires. We also show that the model performed at the level of three sleep medicine specialists, who used clinical experience to predict AHI based on 3D scan displays. Finally, we created topographic displays of the most important facial features used by the model to predict AHI, showing importance of the neck and chin area. The proposed algorithm has potential to serve as an inexpensive and efficient screening tool for individuals with suspected OSA.

Reversed-engineered human alveolar lung-on-a-chip model

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

Phrenic and Hypoglossal motor unit pathology in a Spinocerebellar ataxia type 7 mouse model

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by a deleterious CAG repeat expansion in the coding region of the ataxin-7 gene on chromosome 3. Patients with infantile SCA-7 have the largest repeat expansion (>200 repeats) and the most severe disease characterized by progressive loss of coordination, dysarthria, dysphagia and retinal degeneration. Death in these infants results from severe hypotonia, aspiration pneumonia and respiratory failure. To understand the mechanism behind aspiration and respiratory failure in SCA7, we comprehensively examined hypoglossal (XII) and phrenic neuropathology of a mouse model of infantile SCA7: the SCA7-266Q mice. Previously, we showed that SCA7-266Q mice exhibit progressive respiratory dysfunction along with irregular breathing and prolonged apneic events by 9-11 weeks of age. In this study, we performed post-mortem histological analysis of the XII and phrenic motor neurons and nerves in SCA-7 and WT control mice at 9 weeks of age. Specifically, we studied the presence of glial cells and the degree of neurodegeneration within these motor nuclei. We also performed g-ratio analysis on semi-thin sections of the XII and phrenic nerves. Finally, using electron microscopy, we examined the mitochondrial and myelin pathology in XII and phrenic nerves. The phrenic motor neurons exhibit enhanced neurodegeneration, exacerbated astrogliosis and microglial recruitment in the motor neuron pool. In addition, the XII and phrenic nerves of SCA7-266Q mice have increased g-ratio compared to WT controls which signifies thinning of myelin sheaths and is consistent with demyelination. Furthermore, EM images of the XII and phrenic nerves demonstrate an increase in size of mitochondria in SCA7-266Q mice compared to their WT controls. Finally, preliminary qPCR data exhibited an anomaly in the expression of the neuromuscular junction markers in the diaphragm of the SCA7-266Q mice. Clinically, these findings underscore the importance of respiratory neuropathology that is responsible for the dysphagia, aspiration pneumonia and respiratory failure seen in infantile SCA7.

Perceptual snoring as a basis for a psychoacoustical modeling and clinical patient profiling.

The perceptual burden and social nuisance for mainly the co-sleeper can affect the relationship between snorer and bedpartner. Mandibular advancement devices (MAD) are commonly recommended to treat sleep-related breathing such as snoring or sleep apnea. There is no consensus about the definition of snoring particularly with MAD, which is essential for assessing the effectiveness of treatment. We aimed to stablish a notion of perceptual snoring with MAD in place. Sound samples, each 30 min long, were recorded during in-home, overnight, automatic mandibular repositioning titration studies in a population of 29 patients with obstructive sleep apnea syndrome (OSAS) from a clinical trial carried out to validate the MATRx plus. Three unspecialized and calibrated raters identified sound events and classified them as noise, snore, or breathing as well as providing scores for classification certainty and annoyance. Data were analyzed with respect to expiration-inspiration, duration, annoyance, and classification certainty. A Fleiss' kappa (>0.80) and correlation duration of events (>0.90) between raters were observed. Prevalence of all breath sounds: snore 55.6% (N = 6398), breathing sounds 31.7% (N = 3652), and noise 9.3% (N = 1072). Inspiration occurs in 88.3% of events, 96.8% contained at least on expiration phase. Snore and breath events had similar duration, respectively 2.58s (sd 1.43) and 2.41s (sd 1.22). Annoyance is lowest for breathing events (8.00 sd 0.98) and highest for snore events (4.90 sd 1.92) on a VAS from zero to ten. Perceptual sound events can be a basis for analysis in a psychosocial context. Perceived snoring occurs during both expiration as well as inspiration. Substantial amount of snoring remains despite repositioning of the mandible aimed at the reduction of AHI-ODI.

Classification of sleep apnea based on EEG sub-band signal characteristics

Sleep apnea syndrome (SAS) is a disorder in which respiratory airflow frequently stops during sleep. Alterations in electroencephalogram (EEG) signal are one of the physiological changes that occur during apnea, and can be used to diagnose and monitor sleep apnea events. Herein, we proposed a method to automatically distinguish sleep apnea events using characteristics of EEG signals in order to categorize obstructive sleep apnea (OSA) events, central sleep apnea (CSA) events and normal breathing events. Through the use of an Infinite Impulse Response Butterworth Band pass filter, we divided the EEG signals of C3-A2 and C4-A1 into five sub-bands. Next, we extracted sample entropy and variance of each sub-band. The neighbor composition analysis (NCA) method was utilized for feature selection, and the results are used as input coefficients for classification using random forest, K-nearest neighbor, and support vector machine classifiers. After a 10-fold cross-validation, we found that the average accuracy rate was 88.99%. Specifically, the accuracy of each category, including OSA, CSA and normal breathing were 80.43%, 84.85%, and 95.24%, respectively. The proposed method has great potential in the automatic classification of patients' respiratory events during clinical examinations, and provides a novel idea for the development of an automatic classification system for sleep apnea and normal events without the need for expert intervention.

A Hilbert-based method for processing respiratory timeseries

In this technical note, we introduce a new method for estimating changes in respiratory volume per unit time (RVT) from respiratory bellows recordings. By using techniques from the electrophysiological literature, in particular the Hilbert transform, we show how we can better characterise breathing rhythms, with the goal of improving physiological noise correction in functional magnetic resonance imaging (fMRI). Specifically, our approach leads to a representation with higher time resolution and better captures atypical breathing events than current peak-based RVT estimators. Finally, we demonstrate that this leads to an increase in the amount of respiration-related variance removed from fMRI data when used as part of a typical preprocessing pipeline.Our implementation is publicly available as part of the PhysIO package, which is distributed as part of the open-source TAPAS toolbox (https://translationalneuromodeling.org/tapas).

Abstract 17184: An Increase in the Respiratory Effort Immediately Intensifies the Hemodynamic Congestion; a Mechanism for Progressive Cardiac Decompensation

Introduction: An increase in the pulmonary wedge pressure (PCWP) is associated with an increase in the respiratory effort and the sensation of dyspnea. Hypothesis: We investigated the inverse cause and effect relationship, whether an increase in the respiratory effort can by itself aggravate the hemodynamic congestion. Methods: We scrutinized the cardiopulmonary interactions by simultaneously measuring hemodynamic and respiratory indices in heart failure (HF) patients undergoing right heart catheterization. The immediate effects of the respiratory effort on the hemodynamic indices were analyzed by asking the patients to perform short events of apnea and intentional vigorous breathing. The cardiac waves are superimposed on the respiratory waves in the PCWP. To quantify the respiratory effort, the PCWP was decomposed into cardiac and respiratory waves. The respiratory effort (PRESP) was defined as the peak to peak swing in the respiratory wave that modulated the PCWP. Results: HF patients (n=38) exhibited a high PRESP of 9.0±3.2 mmHg, ~3.5-fold higher than the reported normal respiratory effort. The end-expiratory PCWP rose with PRESP, by 0.83±0.06 mmHg for every 1 mmHg of PRESP (p&lt;0.01). The pulmonary artery pressure (PAP) rose with PRESP by 1.40±0.09 mmHg for every 1 mmHg of PRESP. The changes in the respiratory effort had immediate effect on PCWP, within a single breathing-cycle (t =1.67±0.40 s) in all patients. Interestingly, similar changes in the PCWP with PRESP were obtained in all the patients, independently of the HF etiology. Conclusions: An increase in the respiratory effort is not just a result of cardiac decompensation. The respiratory effort has immediate detrimental effects on the PCWP, PAP and the workloads of the heart. The results highlight the existence of a cardiopulmonary vicious cycle the can lead to progressive decompensation, where the respiratory effort plays a pivotal role.