Neuromedin B-Expressing Neurons in the Retrotrapezoid Nucleus Regulate Respiratory Homeostasis and Promote Stable Breathing in Adult Mice.

Respiratory chemoreceptor activity encoding arterial Pco2 and Po2 is a critical determinant of ventilation. Currently, the relative importance of several putative chemoreceptor mechanisms for maintaining eupneic breathing and respiratory homeostasis is debated. Transcriptomic and anatomic evidence suggests that bombesin-related peptide Neuromedin-B (Nmb) expression identifies chemoreceptor neurons in the retrotrapezoid nucleus (RTN) that mediate the hypercapnic ventilatory response, but functional support is missing. In this study, we generated a transgenic Nmb-Cre mouse and used Cre-dependent cell ablation and optogenetics to test the hypothesis that RTN Nmb neurons are necessary for the CO2-dependent drive to breathe in adult male and female mice. Selective ablation of ∼95% of RTN Nmb neurons causes compensated respiratory acidosis because of alveolar hypoventilation, as well as profound breathing instability and respiratory-related sleep disruption. Following RTN Nmb lesion, mice were hypoxemic at rest and were prone to severe apneas during hyperoxia, suggesting that oxygen-sensitive mechanisms, presumably the peripheral chemoreceptors, compensate for the loss of RTN Nmb neurons. Interestingly, ventilation following RTN Nmb -lesion was unresponsive to hypercapnia, but behavioral responses to CO2 (freezing and avoidance) and the hypoxia ventilatory response were preserved. Neuroanatomical mapping shows that RTN Nmb neurons are highly collateralized and innervate the respiratory-related centers in the pons and medulla with a strong ipsilateral preference. Together, this evidence suggests that RTN Nmb neurons are dedicated to the respiratory effects of arterial Pco2/pH and maintain respiratory homeostasis in intact conditions and suggest that malfunction of these neurons could underlie the etiology of certain forms of sleep-disordered breathing in humans.SIGNIFICANCE STATEMENT Respiratory chemoreceptors stimulate neural respiratory motor output to regulate arterial Pco2 and Po2, thereby maintaining optimal gas exchange. Neurons in the retrotrapezoid nucleus (RTN) that express the bombesin-related peptide Neuromedin-B are proposed to be important in this process, but functional evidence has not been established. Here, we developed a transgenic mouse model and demonstrated that RTN neurons are fundamental for respiratory homeostasis and mediate the stimulatory effects of CO2 on breathing. Our functional and anatomic data indicate that Nmb-expressing RTN neurons are an integral component of the neural mechanisms that mediate CO2-dependent drive to breathe and maintain alveolar ventilation. This work highlights the importance of the interdependent and dynamic integration of CO2- and O2-sensing mechanisms in respiratory homeostasis of mammals.

Assessment of Sleep Disorders in Patients with CVID.

Inborn errors of immunity have been associated with reduced health-related quality of life and increased fatigue. Sleep disorders, which have been shown to contribute to fatigue and other health concerns, are prevalent in the general population, but there are limited studies evaluating these conditions in patients with common variable immunodeficiency (CVID). Our aim was to evaluate the prevalence of fatigue, sleep disturbances, and sleep-disordered breathing in adults with CVID. Patients completed 4 validated, self-administered questionnaires and a 1-night disposable home sleep apnea test. Our results demonstrated increased median Patient-Reported Outcomes Measurement Information System fatigue scores of 58.7 in patients with CVID in addition to clinically significant fatigue as measured by Fatigue Severity Scale score (median, 5.2) and overall poor sleep quality based on global Pittsburgh Sleep Quality Index score (median, 9.0). For CVID patients who completed the home sleep apnea test, 76.9% met criteria for sleep-disordered breathing with an Apnea-Hypopnea Index score of 5 or greater. The results of our study indicate that patients with CVID may have increased rates of undiagnosed sleep disorders that may contribute to increased fatigue and reduced health-related quality of life.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Immediate Effect of Continuous Positive Airway Pressure Therapy on Sleep and Respiration in Patients with Multiple System Atrophy and Sleep-Disordered Breathing.

BACKGROUND: Sleep-disordered breathing (SDB; including stridor and sleep apnea syndromes) is frequent in multiple system atrophy (MSA), but the immediate effect of continuous positive airway pressure (CPAP) therapy is incompletely determined. OBJECTIVE: We sought to evaluate the acute effect and safety of CPAP therapy on SDB and sleep architecture, as well as the clinical characteristics of nonresponders to CPAP therapy. METHODS: The measures of 63 consecutive patients with MSA who underwent a video-polysomnography during two consecutive nights (a first night in ambient air, a second night with or without CPAP, depending on the presence of SDB and availability of CPAP) in routine care were retrospectively collected. Linear mixed models assessed the two-night change in sleep and respiratory measures, comparing those with and without the CPAP therapy on the second night. RESULTS: SDB was frequent and mainly associated with the cerebellar phenotype. The introduction of CPAP had immediate benefits, including the normalization of the apnea-hypopnea index and a resolution of stridor in more than two-thirds of the cases, decreased arousal index, and increased rapid eye movement sleep. CPAP therapy was well tolerated, and only two patients had emergent central apneas. Nonresponse to CPAP was generally associated with more severe motor disease. CONCLUSIONS: CPAP seems a well-tolerated and effective therapy in patients with MSA and SDB in the short term. This treatment shows remarkable immediate benefits by objectively improving both respiratory disturbances and sleep architecture. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Evaluation and management of dyspnea as the dominant presenting feature in neuromuscular disorders.

Dyspnea is a common symptom in neuromuscular disorders and, although multifactorial, it is usually due to respiratory muscle involvement, associated musculoskeletal changes such as scoliosis or, in certain neuromuscular conditions, cardiomyopathy. Clinical history can elicit symptoms such as orthopnea, trepopnea, sleep disruption, dysphagia, weak cough, and difficulty with secretion clearance. The examination is essential to assist with the diagnosis of an underlying neurologic disorder and determine whether dyspnea is from a cardiac or pulmonary origin. Specific attention should be given to possible muscle loss, use of accessory muscles of breathing, difficulty with neck flexion/extension, presence of thoraco-abdominal paradox, conversational dyspnea, cardiac examination, and should include a detailed neurological examination directed at the suspected differential diagnosis. Pulmonary function testing including sitting and supine spirometry, measures of inspiratory and expiratory muscle strength, cough peak flow, sniff nasal inspiratory pressure, pulse oximetry, transcutaneous CO2, and arterial blood gases will help determine the extent of the respiratory muscle involvement, assess for hypercapnic or hypoxemic respiratory failure, and qualify the patient for noninvasive ventilation when appropriate. Additional testing includes dynamic imaging with sniff fluoroscopy or diaphragm ultrasound, and diaphragm electromyography. Polysomnography is indicated for sleep related symptoms that are not otherwise explained. Noninvasive ventilation alleviates dyspnea and nocturnal symptoms, improves quality of life, and prolongs survival. Therapy targeted at neuromuscular disorders may help control the disease or favorably modify its course. For patients who have difficulty with secretion clearance, support of expiratory function with mechanical insufflation-exsufflation, oscillatory devices can reduce the aspiration risk.

Self-applied somnography: technical feasibility of electroencephalography and electro-oculography signal characteristics in sleep staging of suspected sleep-disordered adults.

Sleep recordings are increasingly being conducted in patients' homes where patients apply the sensors themselves according to instructions. However, certain sensor types such as cup electrodes used in conventional polysomnography are unfeasible for self-application. To overcome this, self-applied forehead montages with electroencephalography and electro-oculography sensors have been developed. We evaluated the technical feasibility of a self-applied electrode set from Nox Medical (Reykjavik, Iceland) through home sleep recordings of healthy and suspected sleep-disordered adults (n = 174) in the context of sleep staging. Subjects slept with a double setup of conventional type II polysomnography sensors and self-applied forehead sensors. We found that the self-applied electroencephalography and electro-oculography electrodes had acceptable impedance levels but were more prone to losing proper skin-electrode contact than the conventional cup electrodes. Moreover, the forehead electroencephalography signals recorded using the self-applied electrodes expressed lower amplitudes (difference 25.3%-43.9%, p < 0.001) and less absolute power (at 1-40 Hz, p < 0.001) than the polysomnography electroencephalography signals in all sleep stages. However, the signals recorded with the self-applied electroencephalography electrodes expressed more relative power (p < 0.001) at very low frequencies (0.3-1.0 Hz) in all sleep stages. The electro-oculography signals recorded with the self-applied electrodes expressed comparable characteristics with standard electro-oculography. In conclusion, the results support the technical feasibility of the self-applied electroencephalography and electro-oculography for sleep staging in home sleep recordings, after adjustment for amplitude differences, especially for scoring Stage N3 sleep.

Craniofacial risk factors for obstructive sleep apnea-systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is caused by temporary partial or complete constriction of the upper airway during sleep which leads to reduced blood oxygen and cardiovascular risks. Main symptoms vary between adults and children leading to misdiagnosis or delayed patient identification. To improve early diagnosis, lateral cephalograms can provide craniofacial measurements associated with a higher risk of OSA. In order to identify the most relevant craniofacial measurements, a systematic literature review with meta-analysis was conducted combining the terms 'orthodontic*', 'craniofacial', 'cephalometr*', 'cephalogram', 'OSA*', 'UARS', 'SDB', 'sleep disordered breathing', 'sleep apnea' and 'sleep apnoea'. Of 3016 publications, 19 were included in the systematic review and meta-analysis, 15 with adult patients and four with children. A total of 16 measurements (six angles, 10 distances) were compared, nine showed a possible influence in patients with OSA compared to controls: NSBa angle (-0.28°), ANB angle (+0.33°), ML-NSL angle (+0.34°), Me-Go-Ar angle (+0.33°), SN distance (-0.70 mm), N-ANS distance (-0.36 mm), MP-H distance (+1.18 mm), uvula length (+1.07 mm) and thickness (+0.96 mm). Posterior airway measurements were not sufficiently described or comparably measured to be statistically analysed. There is some evidence for altered craniofacial anatomy in patients with OSA compared to controls. Lateral cephalograms should be screened for these aspects routinely to improve early diagnosis of OSA and craniofacial orthopaedics should complement the interdisciplinary treatment plan for young patients with OSA.

The role of atypical deglutition in children and adolescents with moderate to severe obstructive sleep apnea syndrome.

This cross-sectional study aimed to assess the prevalence of atypical deglutition (tongue thrust) in children diagnosed with moderate to severe obstructive sleep apnea syndrome (OSAS) and to explore its associations, particularly in relation to the type of dentition (mixed or permanent). The study was conducted over a 5 year period at a paediatric hospital in Paris, France. Children aged 6-18 years with moderate to severe OSAS (apnea-hypopnea index ≥5/h) underwent a comprehensive evaluation, including the recording of demographic data, symptoms of snoring and breathing issues, and otolaryngology examination. The swallowing pattern was assessed and orthodontic evaluations were performed. Cephalometric radiography and pharyngometry tests (pharyngeal collapsibility was computed) were conducted. The study found a high prevalence of atypical deglutition in children with mixed 74% [56-87] or permanent 38% [25-51] dentition. In children with mixed dentition and atypical deglutition, the pharyngeal compliance and lower facial dimensions were increased. In children with permanent dentition, atypical deglutition was associated with more severe OSAS and a lower hyoid bone position. Independent of the type of dentition, atypical deglutition was associated with an increase in the apnea-hypopnea index, an increase in the lower facial dimension, increased pharyngeal compliance, and a more caudal hyoid bone position. Atypical deglutition was strongly associated with increased pharyngeal collapsibility, more severe OSAS and altered facial measurements in children. The findings suggest that identifying atypical deglutition in children with OSAS could help to guide a personalised therapeutic approach, including myofunctional therapy.

A sleep stage estimation algorithm based on cardiorespiratory signals derived from a suprasternal pressure sensor.

Automatic estimation of sleep structure is an important aspect in moving sleep monitoring from clinical laboratories to people's homes. However, the transition to more portable systems should not happen at the expense of important physiological signals, such as respiration. Here, we propose the use of cardiorespiratory signals obtained by a suprasternal pressure (SSP) sensor to estimate sleep stages. The sensor is already used for diagnosis of sleep-disordered breathing (SDB) conditions, but besides respiratory effort it can detect cardiac vibrations transmitted through the trachea. We collected the SSP sensor signal in 100 adults (57 male) undergoing clinical polysomnography for suspected sleep disorders, including sleep apnea syndrome, insomnia, and movement disorders. Here, we separate respiratory effort and cardiac activity related signals, then input these into a neural network trained to estimate sleep stages. Using the original mixed signal the results show a moderate agreement with manual scoring, with a Cohen's kappa of 0.53 in Wake/N1-N2/N3/rapid eye movement sleep discrimination and 0.62 in Wake/Sleep. We demonstrate that decoupling the two signals and using the cardiac signal to estimate the instantaneous heart rate improves the process considerably, reaching an agreement of 0.63 and 0.71. Our proposed method achieves high accuracy, specificity, and sensitivity across different sleep staging tasks. We also compare the total sleep time calculated with our method against manual scoring, with an average error of -1.83 min but a relatively large confidence interval of ±55 min. Compact systems that employ the SSP sensor information-rich signal may enable new ways of clinical assessments, such as night-to-night variability in obstructive sleep apnea and other sleep disorders.

Obstructive sleep apnea and cognitive functioning in the older general population: The moderating effect of age, sex, ApoE4, and obesity.

Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.

Obstructive sleep apnea may induce sleep-wake cycle dysregulation: An actigraphic study.

Obstructive sleep apnea (OSA) causes sleep fragmentation and excessive daytime sleepiness (EDS). OSA has been hypothesised to impair the circadian sleep-wake rhythm, and this dysregulation may in turn exacerbate OSA-related diurnal symptoms. Hence, this study aimed to assess the sleep-wake rhythm through actigraphy, and its relationship with EDS in patients with untreated OSA. Patients with moderate-severe OSA (apnea-hypopnea index ≥15/h) and healthy controls (HC) underwent a 7-day actigraphic recording to evaluate the sleep-wake rhythm. Participants underwent a sleep medicine visit and completed the self-report questionnaires assessing EDS (Epworth sleepiness scale, ESS), sleep quality (Pittsburgh sleep quality index, PSQI), and chronotype (morningness-eveningness questionnaire, MEQ). This study included 48 OSA patients (72.9% males; mean age 56.48 ± 9.53 years), and 22 HC (45.5% males; mean age 53.73 ± 18.20 years). After controlling for MEQ scores, actigraphic recording showed that the OSA patients present a lower sleep time (p = 0.011) and sleep efficiency (p = 0.013), as well as a higher sleep latency (p = 0.047), and sleep fragmentation (p = 0.029) than the HC. Regarding the sleep-wake rhythm actigraphic parameters, the OSA patients showed a lower average activity during the most active 10-hour period (p = 0.036) and a lower day/night activity ratio (p = 0.007) than the HC. Patients with OSA also reported higher ESS (p = 0.005) and PSQI scores (p < 0.001), and a chronotype less of morning type (p = 0.027) than the HC. In conclusion, this study documented a reduced diurnal motor activity and lower day/night activity ratio in OSA patients than in controls. These findings suggest a dysregulation of the circadian sleep-wake rhythm in OSA, possibly related to both EDS and reduced daytime motor activity.

Spectrum of sleep-disordered breathing and quality of sleep in adolescent and adult patients with spinal muscular atrophy.

Sleep-disordered breathing is common among children with spinal muscular atrophy, but has been hardly studied among adult subjects. Little is known about sleep quality in spinal muscular atrophy. The aims of this study were to evaluate occurrence and characteristics of sleep-disordered breathing and subjective sleep quality among adolescent and adult patients with spinal muscular atrophy type 2 or 3. Twenty patients aged 33.9 ± 15.2 years were studied. They underwent nocturnal cardiorespiratory monitoring, lung and muscular function evaluation, and were administered the Pittsburgh Sleep Quality Index questionnaire. Nineteen patients showed sleep-disordered breathing, with obstructive events in seven subjects and non-obstructive events in the remaining 12. In the latter group, 10 patients showed pseudo-obstructive hypopneas. Patients with non-obstructive sleep-disordered breathing were younger (p = 0.042), had a lower body mass index (p = 0.0001), were more often affected by spinal muscular atrophy type 2 (p = 0.001), and showed worse impairment of respiratory function than patients with obstructive sleep-disordered breathing. Ten patients were classified as poor sleepers and 10 patients good sleepers. In the whole sample, sniff nasal inspiratory pressure proved to be the only independent predictor of sleep quality (p = 0.009). In conclusion, sleep-disordered breathing is common even among adult patients with spinal muscular atrophy type 2 and 3, and may show either obstructive or different types on non-obstructive features. A worse respiratory muscle function is associated to non-obstructive sleep-disordered breathing and poorer sleep quality. Sleep quality should receive greater attention especially in patients with spinal muscular atrophy type 2, who have a poorer respiratory muscle function, as it could affect their quality of life.

The role of physical activity on obstructive sleep apnea severity and hypoxic load, and the mismatch between subjective and objective physical activity assessments.

Obesity is the primary risk factor for the development of obstructive sleep apnea, and physical inactivity plays an important role. However, most studies have either only evaluated physical activity subjectively or objectively in obstructive sleep apnea. The objectives of this study were: (i) to assess the relationship between obstructive sleep apnea severity (both apnea-hypopnea index and desaturation parameters) and both objectively and subjectively measured physical activity after adjustment for anthropometry and body composition parameters; and (ii) to assess the relationship between objective and subjective physical activity parameters and whether obstructive sleep apnea severity has a modulatory effect on this relationship. Fifty-four subjects (age 47.7 ± 15.0 years, 46% males) were categorized into groups according to obstructive sleep apnea severity: no obstructive sleep apnea; mild obstructive sleep apnea; and moderate-to-severe obstructive sleep apnea. All subjects were evaluated with subjective and objective physical activity, anthropometric and body composition measurements, and 3-night self-applied polysomnography. A one-way ANOVA was used to evaluate the differences between the three obstructive sleep apnea severity groups and multiple linear regression to predict obstructive sleep apnea severity. Differences in subjectively reported sitting time (p ≤ 0.004) were found between participants with moderate-to-severe obstructive sleep apnea, and those with either mild or no obstructive sleep apnea (p = 0.004). Age, body mass index and neck circumference explained 63.3% of the variance in the apnea-hypopnea index, and age, body mass index and visceral adiposity explained 67.8% of the variance in desaturation parameters. The results showed that the person's physical activity does not affect obstructive sleep apnea severity. A weak correlation was found between objective and subjective physical activity measures, which could be relevant for healthcare staff encouraging patients with obstructive sleep apnea to increase their physical activity.

Early sleep apnea treatment in stroke (eSATIS) - a multicentre, randomised controlled, rater-blinded, clinical trial: The association of post-stroke cognition with sleep-disordered breathing and its treatment.

Sleep-disordered breathing (SDB) is linked to cognitive dysfunction. Although SDB is common in stroke patients, the impact of SDB and its early treatment on cognitive functioning after stroke remains poorly investigated. Therefore, we explored the association between SDB and post-stroke cognitive functioning, including the impact of early SDB treatment with adaptive servo-ventilation (ASV) on cognitive recovery from acute event to 3 months post-stroke. We used data from two studies, which included ischaemic stroke patients (n = 131) and no-stroke controls (n = 37) without SDB (apnea-hypopnea index, AHI <5/h) and with SDB (AHI≥20/h). Cognitive functioning was assessed within 7 days and 3 months post-stroke in stroke patients, or at study inclusion in no-stroke control group, respectively. Stroke patients with SDB were randomized to ASV treatment (ASV+) or usual care (ASV-). Linear regression adjusted for main confounders assessed the impact of SDB and its treatment on cognitive recovery. The intention-to-treat analysis did not show significant associations of SDB ASV+ (n = 30) versus SDB ASV- (n = 29) with cognitive recovery. In an exploratory subanalysis, compliant SDB ASV+ (n = 14) versus SDB ASV- showed improvements with ASV in visual memory and cognitive flexibility. Combining the stroke and non-stroke datasets, SDB (n = 85) versus no-SDB (n = 83) was associated with deficits in visual memory and response inhibition independently of stroke. SDB ASV- versus no-SDB (n = 51) was associated with less improvement in visual memory. There was no substantial evidence for benefits of intention-to-treat ASV on cognitive recovery. Exploratory analysis indicated that compliant ASV treatment could benefit visual memory and cognitive flexibility, whereas untreated SDB could contribute to a poor recovery of visual memory.

The association of diabetes with progression of sleep-disordered breathing based on a prospective cohort.

AIM: Prospective studies suggest that sleep-disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep-disordered breathing. METHODS: The participants from Sleep Heart Health Study underwent two polysomnograms at a 5-year interval. The relationship of baseline diabetes to change in the apnoea-hypopnoea index (AHI) was examined based on general linear models, adjusting for demographics, lifestyles, history of hypertension, pulmonary function, length of follow-up and baseline AHI. RESULTS: In total, 161 of the 2603 participants were diagnosed with diabetes at the first polysomnograms. Compared with participants without diabetes, those with diabetes had a higher baseline and larger increases in follow-up AHI and obstructive apnoea index (oAI). Diabetes increased 2.52 events per hour (95% confidence interval 0.45-4.59; p = .017) for AHI change and 1.13 events per hour (95% confidence interval 0.04-2.23; p = .042) for oAI change, respectively. In addition, subgroup analysis suggested that the association was consistent across baseline obstructive sleep apnoea severity and body mass index groups. CONCLUSIONS: Baseline diabetes was associated with worsening sleep-disordered breathing over 5 years, which mainly increased the change in AHI and oAI.

Metabolic Syndrome, Modifiable Lifestyle Factors, and Sleep-Disordered Breathing: The Hispanic Community Health Study.

BACKGROUND: US Hispanics/Latinos are disproportionately susceptible to metabolic syndrome (MetS), attributed in part to systemic inequities related to health and lifestyle factors such as low physical activity (PA) levels, diet quality, alcohol use, tobacco use, and sleep disorder. Gender and heritage group differences are vastly understudied and need to be examined in this heterogeneous population. PURPOSE: To examine the relationships between select health and lifestyle factors and MetS among Hispanic gender and heritage subgroups (Hypothesis 1) and determine whether gender and heritage moderate those relationships (Hypothesis 2). METHODS: Participants included 14,155 Hispanic Americans aged 18-76 (59% female, mean age 45.92 ± 13.97) from seven heritage subgroups. This secondary analysis of cross-sectional data from the observational Hispanic Community Health Study/Study of Latinos (HCHS/SOL) dataset used hierarchical multinomial logistic regression to test Hypothesis 1; the dependent variable, MetS, included three categories delineating absence of MetS and presence of MetS with or without related medication use. Hayes' PROCESS macro tested Hypothesis 2. RESULTS: Low PA and sleep-disordered breathing (SDB) each had significant (p < .001) predictive value of MetS group membership, whereas both low and high alcohol use (p < .001) were associated with decreased MetS risk. Cigarette pack-years were not significantly associated with MetS outcomes. Gender moderated the association between MetS and alcohol use (p < .001), cigarette pack-years (p < .001), and SDB (p < .001) such that the effects on MetS were higher in females than males. The association between MetS and diet quality (p < .001) was stronger among males than in females. CONCLUSIONS: Gender and heritage differences were prominent among study variables.

A Position Modification Device for the Prevention of Supine Sleep During Pregnancy: A Randomised Crossover Trial.

OBJECTIVE: To assess the effectiveness and acceptability of a pillow-like position modification device to reduce supine sleep during late pregnancy, and to determine the impacts on the severity of sleep-disordered breathing (SDB) and foetal well-being. DESIGN: Randomised cross-over study. SETTING AND POPULATION: Individuals in the third trimester of pregnancy receiving antenatal care at a tertiary maternity hospital in Australia. METHODS: Participants used their own pillow for a control week and an intervention pillow for a week overnight, in randomised order. Sleep position and total sleep time for each night of both weeks were objectively monitored, with a sleep study and foetal heart rate monitoring performed on the last night of each week. MAIN OUTCOME MEASURES: Primary outcome = percentage of sleep time in the supine position; secondary outcomes = apnoea-hypopnoea index, foetal heart rate decelerations and birthweight centile. RESULTS: Forty-one individuals were randomised with data collected on 35 participants over 469 nights. There was no difference in percentage of total sleep time in the supine position overnight between the control or intervention pillow week (13.0% [6.1, 25.5] vs. 16.0% [5.6, 27.2], p = 0.81 with a mean difference of 2.5% [95% CI] = -0.7, 5.6, p = 0.12), and no difference in the severity of SDB or foetal heart rate decelerations across weeks. However, increased supine sleep was significantly related to a higher apnoea-hypopnoea index (rs = 0.37, p = 0.003), lower birthweight (rs = -0.45, p = 0.007) and lower birthweight centile (rs = -0.45, p = 0.006). The proportion of supine sleep each night of the week varied widely both within and across participants, despite awareness of side-sleeping recommendations. CONCLUSIONS: We found no evidence to suggest that the adoption of a pillow designed to discourage supine sleep was effective in late pregnancy, with women spending an average of 1 h per night supine. Alternative devices should be investigated, incorporating lessons learnt from this study to inform trials of supine sleep minimisation in pregnancy. TRIAL REGISTRATION: Clinical Trial: (Australia New Zealand Clinical Trials Registry): ACTRN12620000371998.

DAHOS Study: Efficacy of dapagliflozin in treating heart failure with reduced ejection fraction and obstructive sleep apnea syndrome - A 3-month, multicenter, randomized controlled clinical trial.

BACKGROUND: The recent discovery of new therapeutic approaches to heart failure with reduced ejection fraction (HFrEF), including sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as well as improved treatment of co-morbidities has provided much needed help to HFrEF. In addition, dapagliflozin, one of the SGLT-2 inhibitors, serves as a promising candidate in treating obstructive sleep apnea (OSA) of HFrEF patients due to its likely mechanism of countering the pathophysiology of OSA of HFrEF. METHODS: This 3-month multicenter, prospective, randomized controlled trial enrolled participants with left ventricular ejection fraction (LVEF) less than 40% and apnea-hypopnea index (AHI) greater than 15. Participants were randomized into two groups: the treatment group received optimized heart failure treatment and standard-dose dapagliflozin, while the control group only received optimized heart failure treatment. The primary endpoint was the difference in AHI before and after treatment between the two groups. Secondary endpoints included oxygen desaturation index (ODI), minimum oxygen saturation, longest apnea duration, inflammatory factors (CRP, IL-6), quality of life score, and LVEF. RESULTS: A total of 107 patients were included in the final analysis. AHI, LVEF and other baseline data were similar for the dapagliflozin and control groups. After 12 weeks of dapagliflozin treatment, the dapagliflozin group showed significant improvements in sleep parameters including AHI, HI, longest pause time, ODI, time spent with SpO2 < 90%, and average SpO2. Meanwhile, the control group showed no significant changes in sleep parameters, but did demonstrate significant improvements in left ventricular end-diastolic diameter, LVEF, and NT-proBNP levels at 12 weeks. In the experimental group, BMI was significantly reduced, and there were improvements in ESS score, MLHFQ score, and EQ-5D-3L score, as well as significant reductions in CRP and IL-6 levels, while the CRP and IL-6 levels were not improved in the control group. The decrease in LVEF was more significant in the experimental group compared to the control group. There were no significant differences in the magnitude of the decreases between the two groups. CONCLUSIONS: Dapagliflozin may be an effective treatment for heart failure complicated with OSA, and could be considered as a potential new treatment for OSA. (Trial registration  www.chictr.org.cn , ChiCTR2100049834. Registered 10 August 2021).

OSA type-III and neurocognitive function.

Obstructive sleep apnea (OSA) due to a hypertrophy of the adenoids and/or the tonsils in otherwise healthy children is associated with neurocognitive dysfunction and behavioural disorders with various degrees of hyperactivity, aggressiveness, sometimes evolving to a label of attention-deficit hyperactivity disorder. Children with anatomical and/or functional abnormalities of the upper airways represent a very specific population which is at high risk of OSA (also called complex OSA or OSA type III). Surprisingly, the neurocognitive consequences of OSA have been poorly studied in these children, despite the fact that OSA is more common and more severe than in their healthy counterparts. This may be explained by that fact that screening for OSA and sleep-disordered breathing is not systematically performed, the performance of sleep studies and neurocognitive tests may be challenging, and the respective role of the underlining disease, OSA, but also poor sleep quality, is complex. However, the few studies that have been performed in these children, and mainly children with Down syndrome, tend to show that OSA, but even more disruption of sleep architecture and poor sleep quality, aggravate the neurocognitive impairment and abnormal behaviour in these patients, underlining the need for a systematic and early in life assessment of sleep and neurocognitive function and behaviour in children with OSA type III.

Associations between body mass index, sleep-disordered breathing, brain structure, and behavior in healthy children.

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9-11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.