Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Abnormal Activity of Neck Inspiratory Muscles during Sleep as a Prognostic Indicator in Chronic Obstructive Pulmonary Disease.

Rationale: In patients with chronic obstructive pulmonary disease (COPD), increased activity of neck inspiratory muscles has been reported as a compensatory response to hyperinflation-related diaphragmatic dysfunction. The persistence of this activity during sleep could attenuate sleep-related hypoventilation and also negatively impact sleep and clinical outcomes.Objectives: To assess the persistence of neck-muscle activity during sleep in patients with COPD recovering from severe exacerbations (i.e., requiring hospitalization) and its impact on sleep quality and recurrence of exacerbations.Methods: Video polysomnography with neck-muscle EMG was performed in patients with COPD who were recovering from a severe exacerbation. The follow-up period lasted 6 months to record the next severe exacerbation.Measurements and Main Results: Twenty-nine patients were included in the study (median [25th-75th percentile] age, 71 [64-72] yr; 55% male; body mass index, 24 [21-29]; FEV1% predicted, 37 [29-45]; and BODE [body mass index, airflow obstruction, dyspnea, and exercise] index, 6 [5-7]). Twenty-six of these patients exhibited sleep-related neck-muscle activity, which was intermittent (limited to stage 3 sleep) in 17 and permanent throughout sleep in 9. α-Delta EEG activity during stage 3 sleep was observed in 87% of the patients. Compared with patients with no or intermittent neck-muscle activity, those with permanent neck-muscle activity showed more disrupted sleep, had experienced more exacerbations in the previous year, and suffered their next severe exacerbation earlier.Conclusions: Sleep-related neck-muscle activity occurs frequently in patients with COPD who are recovering from a severe exacerbation and seems to negatively affect sleep quality and prognosis; therefore, identification of this activity might improve COPD management after a severe exacerbation.

Patterns of adaptive servo-ventilation settings in a real-life multicenter study: pay attention to volume! : Adaptive servo-ventilation settings in real-life conditions.

BACKGROUNDS: To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). METHODS: The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer's software for 6 months. RESULTS: One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25-75) initial Apnea-Hypopnea-Index of 50 (38-62)/h, an ASV-treatment duration of 2.88 (1.76-4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p < 0.001). MV differences between ASV-F (p = 0.002) and ASV-V (p < 0.001) were not homogenously distributed across clusters, suggesting specific cluster and ASV-algorithm interactions. Individual ASV-data suggest that the hyperventilation risk is not related to the cluster nor the ASV-monitoring type. CONCLUSIONS: Real-life ASV settings are associated with combinations of baseline and follow-up variables wherein cardiological variables remain clinically meaningful. At the patient level, a hyperventilation risk exists regardless of cluster or ASV-monitoring type, spotlighting a future role of MV-telemonitoring in the interest of patient-safety. TRIAL REGISTRATION: The OTRLASV study was registered on ClinicalTrials.gov (Identifier: NCT02429986 ). 1 April 2015.

Postural preinspiratory cortical activity, genioglossus activity and fluid shift in awake obstructive sleep apnoea patients.

NEW FINDING: What is the central question of this study? Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal-dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity? What is the main finding and its importance? The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. ABSTRACT: The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg-positive-pressure application. Moving from the sitting position to the supine position reduces respiratory-related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity.

Adrenergic reactions during N3 sleep arousals in sleepwalking and sleep terrors: The chicken or the egg?

To understand the mechanisms of N3 sleep interruptions in patients with sleepwalking episodes and/or sleep terrors (SW/ST), we evaluated whether autonomic reactions preceded or accompanied behavioural arousals from NREM sleep stage N3. In 20 adult patients with SW/ST and 20 matched controls without parasomnia, heart rate and pulse wave amplitude were measured beat-to-beat during the 10 beats preceding and during the 15 beats succeeding a motor arousal from N3 sleep. Respiratory rate and amplitude were measured during the same 25 successive beats. In patients with SW/ST, the N3 arousals were associated with a 33% increase in heart rate, a 57% decrease in pulse wave amplitude (indicating a major vasoconstriction), a 24% increase in respiratory rate and a doubling of respiratory amplitude. Notably, tachycardia and vasoconstriction started 4 s before motor arousals. A similar profile (tachycardia and vasoconstriction gradually increasing from the 4 s preceding arousal and post-arousal increase of respiratory amplitude, but no polypnea) was also observed, with a lower amplitude, during the less frequent 38 quiet N3 arousals in control subjects. Parasomniac arousals were associated with greater tachycardia, vasoconstriction and polypnea than quiet arousals, with the same pre-arousal gradual increases in heart rate and vasoconstriction. Autonomic arousal occurs 4 s before motor arousal from N3 sleep in patients with SW/ST (with a higher adrenergic reaction than in controls), suggesting that an alarming event during sleep (possibly a worrying sleep mentation or a local subcortical arousal) causes the motor arousal.

Evening sock marks as an adjunct to the clinical prediction of obstructive sleep apnea.

STUDY OBJECTIVES: Fluid overload shifting from the legs to the upper airway during sleep promotes obstructive sleep apnea (OSA) and interventions targeting fluid attenuate OSA. Fluid shift has been previously measured by bioelectrical impedance, a complex and time-consuming technique not applicable in the daily clinical settings. The aim of this study is to evaluate the presence of clinically detectable fluid overload and shift and its association with OSA. METHODS: Patients undergoing sleep study for suspected OSA were asked to report the presence of 11 signs/symptoms associated to excessive accumulation of fluid in different parts of the body at different times of the day. RESULTS: Among 392 patients (male: 53%, median [interquartile range] age: 56 years [1], body mass index, BMI: 29 kg/m2 [2]) included in the study, 135 (34%) had moderate-to-severe OSA (apnea hypopnea index, AHI ≥ 15). Daytime fluid accumulation and nocturnal fluid shift, clinically detectable by patient-reported "evening sock marks," "heavy legs during the day," and "morning stuffed nose," were prevalent in the entire population (46%, 43%, and 33%, respectively). In multivariate analysis, evening sock marks was an independent correlate of having an AHI ≥ 15, together with male sex, older age, and self-reported snoring and apneas. CONCLUSIONS: Clinically detectable fluid overload and shift are prevalent in patients addressed for suspected OSA, and evening sock marks, a marker for leg swelling, is an independent correlate of moderate-to-severe OSA. This sign might contribute to OSA diagnosis and identification of patients likely to be treated by interventions targeting fluid overload and shift.

What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study) : Adaptive servo-ventilation in real-life conditions.

BACKGROUNDS: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. METHODS: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. RESULTS: 177/214 patients were analysed (87.57% male) with a median (IQ25-75) age of 71 (65-77) years, an ASV-treatment duration of 2.88 (1.76-4.96) years, an ASV-usage of 6.52 (5.13-7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6-13.5) to 6 (3-9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38-62)/h to a residual device index of 1.9 (0.7-3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). CONCLUSIONS: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. TRIAL REGISTRATION: The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986 ) on 1 April 2015.

Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans.

NEW FINDINGS: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. ABSTRACT: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory-related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.

Echocardiographic evaluation in subjects with α1-Antitrypsin deficiency.

BACKGROUND: α1-Antitrypsin (AAT) deficiency (AATD) is a genetic condition associated with early-onset panacinar emphysema and, less often, vascular disease. Recently, abnormal elastic properties of ascending aortic wall were described in ZZ genotype AATD subjects who incidentally showed an increased left ventricular mass. MATERIALS AND METHODS: To evaluate biventricular dimensions, valvular apparatus, systolic and diastolic function, 33 AATD subjects with ZZ genotype and 33 healthy subjects matched for age and sex underwent a complete echocardiographic assessment. RESULTS: Compared to controls, AATD subjects showed increased left ventricular mass (160 ± 59 g vs. 121 ± 70 g, P < 0.001), a higher incidence of left and right ventricular diastolic dysfunction (30% vs. 16%, P < 0.001 and 45% vs. 20%, P < 0.001, respectively) and mitral valve prolapse (35% vs. 6%, P < 0.001). In contrast, there was no difference between the two groups in diameters and systolic function of both ventricles and in the ejection fraction of left ventricle. The functions of aortic and tricuspidal valves were also similar. CONCLUSIONS: In the presence of greater left ventricular mass, a significantly higher incidence of left and right ventricular diastolic dysfunction and mitral valve prolapse occurs in AATD subjects (ZZ genotype). These findings strongly suggest an abnormal remodelling process in cardiac tissue in AATD.

Oronasal masks require higher levels of positive airway pressure than nasal masks to treat obstructive sleep apnea.

PURPOSE: The purpose of this study was to compare the therapeutic pressure determined by an automated CPAP device (AutoCPAP) during the titration period, between nasal and oronasal mask and the residual apnea-hypopnea index (AHI) on a subsequent poligraphy performed with the established therapeutic CPAP. METHODS: As a retrospective study, 109 subjects with moderate and severe obstructive sleep apnea-hypopnea (apnea-hypopnea index≥15 events/h) were studied. CPAP titration was performed using an auto-titrating device. RESULTS: There was significant difference in the mean pressure delivered with autoCPAP between the group of patients using the nasal mask (mean 10.0 cmH2O±2.0 SD) and the group which used the oronasal mask (mean 11.2 cmH2O±2.1) (p<0.05). Residual apneas were lower when using a nasal mask: average AHI of 2.6±2.5 compared to 4.5±4.0 using an oronasal mask (p<0.05). On multivariate analysis, the only independent predictor of the level of therapeutic pressure of CPAP was the type of mask used (r=0.245, p 0.008). CONCLUSIONS: Therapeutic CPAP level for OSAH is higher when administered via oronasal mask, leaving more residual events. These findings suggest that nasal mask should be the first choice for OSAH treatment.

Are Depressive Symptoms in Obstructive Sleep Apnea Attributable to a Syndrome of Dysregulation of Rhythms and Hyperactivity (DYMERS)?

Background: Obstructive sleep apnea (OSA) is characterized by repeated airway obstructions during sleep, causing hypopnea, apnea, intermittent hypoxia, and sleep fragmentation. The severity of OSA is measured using the apnea-hypopnea index (AHI), with AHI ≥ 5 indicating OSA. This study aims to assess the frequency and type of depressive disorder characteristics of OSA patients and to evaluate the impact on quality of life, also considering the presence of hyperactivity. Methods: A case-control study using OSA patients referred to Cagliari's sleep disorder center. Controls were matched by age and sex from community databases. OSA diagnoses were made with AHI > 15. Depressive episodes were identified using BDI-SF, and H-QoL (Health related Quality of Life) was measured with the SF-12, focusing on item 10 for hyper-energy. Results: The clinical sample (n = 25) had a higher frequency of depressive episodes (36%) compared to controls (7% and 4%). Depressed OSA patients had worse H-QoL and higher hyper-energy scores, but the additional burden from depression was relatively low. Conclusions: The OSA sample has a higher frequency of depressive episodes compared to the general population. Depressive episodes in OSA patients are linked to higher scores on item 10 of the SF-12, indicating hyper-energy despite lower overall quality of life scores. While OSA significantly impacts quality of life, the additional burden from depression is less severe than in other chronic diseases. These findings suggest that depressive episodes in OSA may be related to rhythm dysregulation and hyperactivity (DYMERS).

Prevalence and Risk by Age and Sex of Sleep Dysregulation and Depressive Episodes in Bipolar and Depressive Disorders in a Community Survey in Sardinia, Italy.

Background/Objectives: Sleep disturbances often accompany mood disorders and persistent insomnia after mood symptoms have resolved may be a marker of poor outcome. The association between sleep symptoms and mood disorders seems to change with age and sex. This study aims to assess the frequency of depressive episodes and sleep disorders in the general population through an agile screening questionnaire and to evaluate the association of depressive episodes and sleep symptoms by sex and age categories. Methods: 774 women and 728 men from Sardinia aged > 16 years old were enrolled. The Patient Health Questionnaire (PHQ-9) was administered through a computer-assisted telephonic interview. Results: The frequency of depressive episodes was double in women (10.6% vs. 4.4%; p < 0.0001), with the highest values in women > 75 yo (17.4%). The frequency of sleep dysregulation was double in women (18.7% vs. 9.6%; p < 0.0001), with the highest values in women > 75 yo (35.9%) and the lowest in the group of men > 75 yo. The group of young males showed the lowest frequency of depressive episodes (1.4%) and a frequency of sleep dysregulation (9.1%) similar to that of the other groups of age and sex. Sleep dysregulation without depressive episodes presented a higher distribution in the elderly, both in males (20.7%) and in females (18.5%). No significative differences were found across sex and age groups in the distribution of depressive episodes without sleep dysregulation. Conclusions: The use of an agile screener such as PHQ9 in the general population and/or in populations at risk can be a valuable tool in finding those individuals in whom sleep dysregulation may represent an early warning signal, one that may be thoroughly evaluated to identify and treat possible sleep disorders early.

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

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

Screening of obstructive sleep apnea syndrome by the deep breathing technique.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with alterations in heart rate variability (HRV) in relation to chronic autonomic dysfunction. We tested the ability of the deep breathing technique-a simple way to evaluate HRV-to identify patients with OSAS. METHODS: Consecutive patients referred for suspected OSAS (without obesity, diabetes, and heart diseases) were included. They underwent a measure of HRV at rest and of heart rate oscillations during expiration vs inspiration (DeltaHRDB) when breathing deeply at the resonant frequency of 6 cycles per minute (deep breathing technique) while sitting awake, followed by a nighttime polysomnography. We measured DeltaHRDB and performed temporal and spectral HRV analysis. RESULTS: Of 31 included participants (77% male), 14 had mild to moderate OSAS (apnea-hypopnea index median [IQR]: 18 [12]) and 17 had no OSAS. The conventional HRV analysis did not reveal any difference between the groups with vs without OSAS. However, the DeltaHRDB was lower in those with than without OSAS. Lower DeltaHRDB correlated with higher apnea-hypopnea index, arousal index, and desaturation degree. A DeltaHRDB below 11 beats per minute (bpm) predicted OSAS with a sensitivity of 100% and specificity of 86%. CONCLUSIONS: The deep breathing technique accurately identifies a reduction in cardiac changes in patients with mild to moderate OSAS. It could be used as a simple screening tool to select patients for polysomnography. CITATION: Onanga M, Joanny S, Rivals I, et al. Screening of obstructive sleep apnea syndrome by the deep breathing technique. J Clin Sleep Med. 2023;19(2):293-302.

Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) patients, respiratory insufficiency is a major burden. Diaphragm conditioning by electrical stimulation could interfere with lung function decline by promoting the development of type 1 muscle fibres. We describe an ancillary study to a prospective, non-randomized trial (NCT00420719) assessing the effects of diaphragm pacing on forced vital capacity (FVC). Sleep-related disturbances being early clues to diaphragmatic dysfunction, we postulated that they would provide a sensitive marker. Stimulators were implanted laparoscopically in the diaphragm close to the phrenic motor point in 18 ALS patients for daily conditioning. ALS functioning score (ALSFRS), FVC, sniff nasal inspiratory pressure (SNIP), and polysomnographic recordings (PSG, performed with the stimulator turned off) were assessed before implantation and after four months of conditioning (n = 14). Sleep efficiency improved (69 ± 15% to 75 ± 11%, p = 0.0394) with fewer arousals and micro-arousals. This occurred against a background of deterioration as ALSFRS-R, FVC, and SNIP declined. There was, however, no change in NIV status or the ALSFRS respiratory subscore, and the FVC decline was mostly due to impaired expiration. Supporting a better diaphragm function, apnoeas and hypopnoeas during REM sleep decreased. In conclusion, in these severe patients not expected to experience spontaneous improvements, diaphragm conditioning improved sleep and there were hints at diaphragm function changes.

Attenuation of obstructive sleep apnea by compression stockings in subjects with venous insufficiency.

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.

Influence of upper airway size on volume exhaled under negative pressure during evaluation of upper airway collapsibility.

STUDY OBJECTIVES: It has been shown that volume exhaled in the first 0.5 s after application at the mouth of 5 cmH(2)O negative pressure (V,NEP(0.5)) during wakefulness strongly reflects critical pressure (Pcrit) during sleep but only in males with neck circumference (NC) >37 cm. The aim of this study was to establish the relationship between upper airway (UA) size and V,NEP(0.5), to obtain V,NEP(0.5) values as percent predicted and then correlate them with Pcrit obtained in the same subjects. PATIENTS AND MEASUREMENTS: In 20 (8 women) normal subjects (age, 39 ± 16 years; BMI, 22.5 ± 3.0 kg/m(2); AHI, 0.8 ± 1.0), NC, mean pharyngeal cross-sectional area (APmean) by acoustic pharyngometry and V,NEP(0.5) in the supine position were measured. Correlations between APmean, NC and V,NEP(0.5) were performed. A strong relationship was found between APmean and NC, and the predicted V,NEP(0.5) values were obtained using the equation derived from the relationship between V,NEP0.5 and NC. Subsequently, nine normal subjects (age, 26.3 ± 2.5 yrs, BMI 23.9 ± 3.2 kg/m(2), AHI 2.3 ± 0.5), ten snorers (age, 68 ± 11 years; BMI, 26.6 ± 4.6 kg/m(2); AHI, 3.5 ± 0.8) and ten OSAH patients (age, 64 ± 9 years; BMI, 32 ± 4.9 kg/m(2); AHI, 43.8 ± 24.4) underwent measurement of V,NEP(0.5) in the supine position while awake and Pcrit during sleep. Correlations between Pcrit and both V,NEP(0.5) and V,NEP(0.5) expressed as percent predicted were performed in all subjects. RESULTS: Controls had V,NEP(0.5) of 387 ± 103 mL (100.1 ± 13% predicted) and Pcrit of -3.7 ± 2.0 cmH(2)O, snorers had V,NEP(0.5) of 320 ± 33 mL (62 ± 12% predicted) and Pcrit of -0.6 ± 0.3 cmH(2)O while OSAH patients had V,NEP(0.5) of 295 ± 67 mL (48 ± 12% predicted) and Pcrit of 1.0 ± 1.0 cmH(2)O. The linear regression analysis showed a close and highly significant correlation between V,NEP(0.5) percent predicted and Pcrit (r (2) = 0.79, p < 0.001). CONCLUSIONS: V,NEP(0.5) expressed as percent predicted according to NC strongly reflects Pcrit in a wide range of values and can be used as a surrogate of Pcrit to assess UA collapsibility independently from UA size and sex.

Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre.

Prader-Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients' caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects.

Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure.

BACKGROUND: Obstructive sleep apnea (OSA) and central sleep apnea are common in patients with heart failure. We hypothesized that in such patients, severity of OSA is related to overnight rostral leg fluid displacement and increase in neck circumference, severity of central sleep apnea is related to overnight rostral fluid displacement and to sleep Pco(2), and continuous positive airway pressure alleviates OSA in association with prevention of fluid accumulation in the neck. METHODS AND RESULTS: In 57 patients with heart failure (ejection fraction or=50% of apneas and hypopneas obstructive) and a central-dominant group (>50% of events central). Patients with OSA received continuous positive airway pressure. In obstructive-dominant patients, there were inverse relationships between overnight change in leg fluid volume and both the overnight change in neck circumference (r=-0.780, P<0.001) and the apnea-hypopnea index (r=-0.881, P<0.001) but not transcutaneous Pco(2). In central-dominant patients, the overnight reduction in leg fluid volume correlated inversely with the apnea-hypopnea index (r=-0.919, P<0.001) and the overnight change in neck circumference (r=-0.568, P=0.013) and directly with transcutaneous Pco(2) (r=0.569, P=0.009). Continuous positive airway pressure alleviated OSA in association with prevention of the overnight increase in neck circumference (P<0.001). CONCLUSIONS: Our findings suggest that nocturnal rostral fluid shift is a unifying concept contributing to the pathogenesis of both OSA and central sleep apnea in patients with heart failure.