Identification of quality-of-life clusters by the Quebec sleep questionnaire in sleep apnea patients.

Patients with obstructive sleep apnea (OSA) may present different symptoms. The clinical importance of symptom clustering is supported by the difference in the incidence of cardiovascular diseases between hypersomnolent and non-hypersomnolent sleep apnea patients. The objective of this study was to determine if quality-of-life clusters could be identified from the Quebec Sleep Questionnaire (QSQ) in OSA patients. Latent class analysis was used to identify clusters in a multivariate analysis of dichotomic variables (presence or absence of symptoms) for each item the QSQ obtained from 147 patients who fulfilled the questionnaire during its validation and subsequent trials (75.5% males, age: 53 ± 11 years, body mass index (BMI): 30.4 ± 4.7 kg/m2, apnea/hypopnea index (AHI): 31.3 ± 14.8/h). Three clusters were identified. Quality of life was preserved in patients of cluster 1 (20.4% of patients). Patients of cluster 2 (32.6% of patients) had a moderately impaired quality of life, mainly due to daytime somnolence and poor sleep quality. Patients with impaired quality of life (cluster 3, 46.9% of patients) had an important impact in every domain of the QSQ with the highest sleepiness and daytime symptom impairments. Gender, BMI, and AHI did not differ between the three clusters. In conclusion, different quality-of-life clusters can be identified from the QSQ in sleep apnea patients. These clusters are similar to those reported previously. Further studies are needed to validate these clusters in larger and independent cohorts, to evaluate how they respond to OSA treatment, and their relationship with incident outcomes.

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain. METHODS: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population. RESULTS: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1). CONCLUSIONS: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).

Impact of continuous positive airway pressure mode on adherence to treatment in obstructive sleep apnea patients awaiting bariatric surgery.

Obstructive sleep apnea is prevalent in the bariatric population, and is associated with various complications. Despite increasing popularity, automatic positive airway pressure has not yet been studied in this population. The objective was to compare treatment adherence between automatic positive airway pressure and fixed positive airway pressure (continuous positive airway pressure) in obstructive sleep apnea patients awaiting bariatric surgery. This randomized controlled trial involved obese patients newly diagnosed with severe obstructive sleep apnea and awaiting bariatric surgery. The primary outcome was the difference in adherence between automatic positive airway pressure and continuous positive airway pressure pre-operatively. Secondary outcomes included positive airway pressure efficacy, adherence at 1 month, adverse effects, quality of life and peri-operative complications. Analyses were conducted using a modified intention-to-treat methodology. Fifty patients were randomized. Baseline characteristics and duration of positive airway pressure therapy were comparable between groups. At the time of surgery, the percentage of overall nights positive airway pressure used was 96.9% [95% confidence interval: 93.5-100] and 86.0% [95% confidence interval: 66.9-100] in the automatic positive airway pressure and continuous positive airway pressure groups, respectively (p = .047). Average use was 6.3 hr per night [95% confidence interval: 5.1-7.2] and 5.9 hr per night [95% confidence interval: 3.0-8.8], with a difference of 0.4 hr favouring automatic positive airway pressure (p = .75). Nightly use ≥ 4 hr per night was 86.4% and 74.0% in the automatic positive airway pressure and fixed continuous positive airway pressure groups, respectively (p = .22). There were no statistically significant differences regarding adherence at 1 month, efficacy parameters, adverse effects, quality of life and peri-operative complications. With no difference on the safety profile and efficiency parameters, treatment adherence is not improved with automatic positive airway pressure compared with fixed continuous positive airway pressure in obstructive sleep apnea patients awaiting bariatric surgery.

Reliability of Home Nocturnal Oximetry in the Diagnosis of Overlap Syndrome in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and sleep apnea are common conditions and often coexist. The proper diagnosis of sleep apnea may affect the management and outcome of patients with COPD. OBJECTIVE: To determine the accuracy of home nocturnal oximetry to distinguish between nocturnal oxygen desaturation related to COPD alone or to sleep apnea in patients with moderate-to-severe COPD who have significant nocturnal hypoxemia with cyclical changes in saturation. METHODS: This study involved a comparison of home nocturnal oximetry and laboratory-based polysomnography (PSG) in patients with moderate-to-severe COPD considered for inclusion in a trial of nocturnal oxygen therapy. All of the patients had significant nocturnal oxygen desaturation (defined as ≥30% of the recording time with a transcutaneous arterial oxygen saturation <90%) with cyclical changes in saturation suggestive of sleep apnea. RESULTS: PSG was obtained in 90 patients; 45 patients (mean age = 68 years, SD = 8; 71% men; mean forced expiratory volume in 1 s [FEV1] = 50.6% predicted value, SD = 18.6%; data from 41 patients) fulfilled the criteria for sleep apnea (mean apnea-hypopnea index = 32.6 events/h, SD = 19.9) and 45 patients (mean age = 69 years, SD = 8; 87% men; mean FEV1 predicted value 44.6%, SD = 15%) did not (mean apnea-hypopnea index = 5.5 events/h, SD = 3.8). None of the patients' characteristics (including demographic, anthropometric, and physiologic measures) predicted the diagnosis of sleep apnea according to PSG results. CONCLUSION: The diagnosis of sleep apnea in patients with moderate to severe COPD cannot rely on nocturnal oximetry alone, even when typical cyclical changes in saturation are seen on oximetry tracing. When suspecting an overlap syndrome, a full-night, in-laboratory PSG should be obtained.

ERS statement on respiratory muscle testing at rest and during exercise.

Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system.

Adherence to CPAP with a nasal mask combined with mandibular advancement device versus an oronasal mask: a randomized crossover trial.

PURPOSE: Evidence for the management of CPAP-treated obstructive sleep apnea suggests that oronasal masks reduce mouth leaks at the expense of higher pressures and poorer adherence. Some authors have proposed the use of mandibular advancement devices in combination with nasal masks to address this. The aim of this study was to assess adherence to CPAP after 1 month's use of a nasal mask with a mandibular advancement device and to compare adherence with an oronasal mask. METHODS: A randomized crossover trial design to assess whether a mandibular advancement device combined with a nasal mask would improve CPAP adherence compared to an oronasal mask. RESULTS: There was no improvement in CPAP adherence and self-reported interface-related pain was significantly higher with the combined treatment. CONCLUSIONS: Although the combined treatment reduced pressures, likely by improving upper airway patency, it may only be appropriate for a small number of patients due to associated discomfort. TRIAL REGISTRATION: NCT01889472.

Ventilatory support or respiratory muscle training as adjuncts to exercise in obese CPAP-treated patients with obstructive sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) and obesity are interdependent chronic diseases sharing reduced exercise tolerance and high cardiovascular risk. INTERVENTION: A 3-month intervention with innovative training modalities would further improve functional capacity and cardiovascular health than usual cycle exercise training in already continuous positive airway pressure (CPAP)-treated obese patients with OSA. METHODS: Fifty three patients (35

Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial.

BACKGROUND: Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT. METHODS: The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years. DISCUSSION: The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).

Maternal sleep-disordered breathing and the risk of delivering small for gestational age infants: a prospective cohort study.

OBJECTIVE: It is unclear whether objectively measured maternal sleep-disordered breathing (SDB) leads to poor fetal outcomes. In this study, we prospectively assessed whether polysomnography-based diagnosis of SDB in the third trimester is associated with the delivery of small for gestational age (SGA) infants. STUDY DESIGN: Participants were recruited from a multicentre pregnancy cohort study. Eligible participants were evaluated for SDB based on symptoms (snoring and/or witnessed apnoeas assessed using the Pittsburgh Sleep Quality Index questionnaire) and in-home complete polysomnography in the third trimester. SGA was defined as <10th centile using customised birthweight centiles adjusted for maternal parity, prepregnancy body mass index (BMI), ethnicity, gestational age and infant sex. RESULTS: Of the 234 pregnant participants who completed a sleep study, 82% were Caucasian, with mean (SD) age of 31 (4.3) years and a prepregnancy BMI of 23 (4) kg/m(2). The delivery of SGA infants occurred in 27 (12%) of the study participants. The symptoms of SDB had poor overall sensitivity and specificity for diagnosing SDB identified by polysomnography. Symptoms of SDB in the third trimester demonstrated a potential association with delivering an SGA infant, however this did not reach statistical significance (OR 2.36 (95% CI 0.85 to 6.54, p=0.10)). However, the odds of delivering an SGA infant were significantly increased with polysomnography-based diagnosis of maternal SDB (using apnoea-hypopnoea index cut-off of 10, OR 2.65 (95% CI 1.15 to 6.10, p=0.02)). CONCLUSIONS: Objectively measured SDB in the third trimester is significantly associated with the delivery of SGA infants.

Diaphragm and genioglossus corticomotor excitability in patients with obstructive sleep apnea and control subjects.

Corticomotor excitability of peripheral muscles appears to be altered in patients with obstructive sleep apnea. However, there is no evidence of such alteration for upper airway/respiratory muscles that are involved in the pathophysiology of this disease. The aim of this study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor excitability in awake healthy subjects versus patients with obstructive sleep apnea. Corticomotor excitability was assessed by transcranial magnetic stimulation in 12 untreated apneic men (48 ± 10 years; body mass index = 28.9 ± 4.7 kg m(-2); apnea-hypopnoea index = 41 ± 23 events per hour) and nine control men (45 ± 10 years; body mass index = 27.3 ± 3.3 kg m(-2); apnea-hypopnoea index = 7 ± 4 events per hour). Assessments included diaphragm and genioglossus expiratory motor thresholds, and transcranial magnetic stimulation-induced motor-evoked potential characteristics obtained while breathing room air or 5% CO2 (random order) and then 7% CO2 both balanced with pure O2. Transcranial magnetic stimulation twitches were applied during early inspiration and end expiration. Diaphragm motor-evoked potential amplitudes increased and expiratory diaphragm motor-evoked potential latencies decreased during CO2-induced increase in ventilatory drive, with no difference in these responses between patients with obstructive sleep apnea and control subjects. Expiratory genioglossus motor-evoked potential amplitudes were significantly lower in patients with obstructive sleep apnea than in control subjects. Baseline activity of the genioglossus increased with increasing FiCO2, this effect being significantly higher in patients with obstructive sleep apnea than in control subjects. However, neither genioglossus motor-evoked potential amplitudes nor latencies were significantly modified with increasing FiCO2 both in patients with obstructive sleep apnea and in control subjects. Corticomotor excitability of genioglossus and diaphragm are not altered during CO2-induced increase in ventilatory drive in patients with obstructive sleep apnea.

Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.

NEW FINDINGS: What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. ABSTRACT: Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (V̇I,max)and minimal inspiratory airflow (V̇I,min),V̇I,max-V̇I,min flow drop (ΔV̇I),oropharyngeal (POro,peak ) and velopharyngeal peak pressures, oropharyngeal k1 /k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp ) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in V̇I,max and an increase in ΔV̇I occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i) rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii) the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the genioglossus; and (iii) rTMS applied during expiration induces corticomotor facilitation.

Acute haemodynamic effects of continuous positive airway pressure in awake patients with heart failure.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) has been used to treat patients with chronic heart failure (CHF) and sleep-disordered breathing (SDB). CPAP treatment in severe CHF with concomitant SDB and atrial fibrillation has been linked to impairment of cardiac output (CO) as a potential cause for adverse outcome. The aim of the present study was to test whether incremental CPAP application in awake CHF patients with SDB, with and without atrial fibrillation, induces acute alterations of blood pressure (BP), heart rate (HR) and CO. METHODS: During daytime, we applied incremental CPAP (4-10 cmH2O) in 37 stable patients with CHF and SDB. BP and HR were assessed after each 1 cmH2O CPAP increase in 5-min intervals in the entire sample, and CO was assessed at one centre (n = 11). RESULTS: Neither mean BP, HR nor CO changed significantly with incremental CPAP (at 0 and 10 cmH2O: 85 ± 2 and 84 ± 2 mm Hg, P = 1.0, 63 ± 1 to 61 ± 2 b.p.m., P = 0.88 and 2.03 ± 0.5 and 2.35 ± 0.8 L/min/m2 , P = 0.92, respectively). No significant differences in maximum BP drop or HR drop between patients with sinus rhythm and atrial fibrillation were found. In 1 of 37 patients, a prespecified event of haemodynamic compromise (drop of mean BP >15 mm Hg) without clinical signs occurred. CONCLUSIONS: These results contribute to the evidence that CPAP does not cause haemodynamic compromise in the vast majority of normotensive CHF patients with SDB.

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

BACKGROUND: Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). OBJECTIVES: The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. METHODS: Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. RESULTS: AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). CONCLUSIONS: ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials.

Preliminary Assessment of an Ambulatory Device Dedicated to Upper Airway Muscle Training in Patients With Sleep Apnea: Proof-of-Concept Study.

BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a prevalent condition affecting a substantial portion of the global population, with its prevalence increasing over the past 2 decades. OSAHS is characterized by recurrent upper airway (UA) closure during sleep, leading to significant impacts on quality of life and heightened cardiovascular and metabolic morbidity. Despite continuous positive airway pressure (CPAP) being the gold standard treatment, patient adherence remains suboptimal due to various factors, such as discomfort, side effects, and treatment unacceptability. OBJECTIVE: Considering the challenges associated with CPAP adherence, an alternative approach targeting the UA muscles through myofunctional therapy was explored. This noninvasive intervention involves exercises of the lips, tongue, or both to improve oropharyngeal functions and mitigate the severity of OSAHS. With the goal of developing a portable device for home-based myofunctional therapy with continuous monitoring of exercise performance and adherence, the primary outcome of this study was the degree of completion and adherence to a 4-week training session. METHODS: This proof-of-concept study focused on a portable device that was designed to facilitate tongue and lip myofunctional therapy and enable precise monitoring of exercise performance and adherence. A clinical study was conducted to assess the effectiveness of this program in improving sleep-disordered breathing. Participants were instructed to perform tongue protrusion, lip pressure, and controlled breathing as part of various tasks 6 times a week for 4 weeks, with each session lasting approximately 35 minutes. RESULTS: Ten participants were enrolled in the study (n=8 male; mean age 48, SD 22 years; mean BMI 29.3, SD 3.5 kg/m2; mean apnea-hypopnea index [AHI] 20.7, SD 17.8/hour). Among the 8 participants who completed the 4-week program, the overall compliance rate was 91% (175/192 sessions). For the tongue exercise, the success rate increased from 66% (211/320 exercises; SD 18%) on the first day to 85% (272/320 exercises; SD 17%) on the last day (P=.05). AHI did not change significantly after completion of training but a noteworthy correlation between successful lip exercise improvement and AHI reduction in the supine position was observed (Rs=-0.76; P=.03). These findings demonstrate the potential of the device for accurately monitoring participants' performance in lip and tongue pressure exercises during myofunctional therapy. The diversity of the training program (it mixed exercises mixed training games), its ability to provide direct feedback for each exercise to the participants, and the easy measurement of treatment adherence are major strengths of our training program. CONCLUSIONS: The study's portable device for home-based myofunctional therapy shows promise as a noninvasive alternative for reducing the severity of OSAHS, with a notable correlation between successful lip exercise improvement and AHI reduction, warranting further development and investigation.

Association between sleep microarchitecture and cognition in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS: Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS: All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018). CONCLUSION: Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

Auto-servoventilation in heart failure with sleep apnoea: a randomised controlled trial.

We tested the hypotheses that in patients with congestive heart failure (CHF) and sleep disordered breathing (SDB) auto-servoventilation (ASV) improves cardiac function and quality of life. Between March 2007 and September 2009, patients with stable CHF (left ventricular ejection fraction (LVEF) ≤ 40%) and SDB (apnoea/hypopnoea index ≥ 20 events · h(-1)) were randomised to receive either ASV (BiPAP ASV (Philips Respironics, Murrysville, PA, USA), n=37) and optimal medical management, or optimal medical management alone (n=35). Outcomes were assessed at baseline and 12 weeks. The apnoea/hypopnoea index assessed with polysomnography scored in one core laboratory was significantly more reduced in the ASV group (-39 ± 16 versus -1 ± 13 events · h(-1); p<0.001) with an average use of 4.5 ± 3.0 h · day(-1). Both groups showed similar improvements of the primary end-point LVEF (+3.4 ± 5 versus +3.5 ± 6%; p=0.915) assessed with echocardiography. In the ASV group, reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly greater (-360 ± 569 versus +135 ± 625 ng · mL(-1); p=0.010). No differences were observed between the groups in subjective quality of life. In patients with CHF and SDB, ASV reduced NT-proBNP levels, but improvement of LVEF or quality of life was not greater than in the control group. The data support that such patients can be randomised in large-scale, long-term trials of positive airway pressure therapy versus control to determine effects on cardiovascular outcome.

Consecutive transcranial magnetic stimulation twitches reduce flow limitation during sleep in apnoeic patients.

NEW FINDINGS: What is the central question of this study? A transcranial magnetic stimulation (TMS)-induced twitch applied on isolated single breaths over the motor cortex somatotopic representation of the tongue briefly recruits submental muscles and improves airflow dynamics of flow-limited respiratory cycles without arousing sleep apnoea patients. However, the mechanical impact of the TMS-induced twitch applied during consecutive breathing cycles on airflow dynamics remains unknown. What is the main finding and what is its importance? Our results show that application of TMS with the stimulator output set at the sleep submental motor threshold intensity on consecutive respiratory cycles increases inspiratory flow and reduces the turbulent airflow component. These results indicate an improvement of airflow pattern after two single consecutive TMS-induced twitches without arousing sleep apnoea patients. Transcranial magnetic stimulation (TMS)-induced twitches applied on isolated breaths briefly recruit upper airway dilator muscles and improve airflow and inspiratory volume without arousing apnoeic patients from sleep, but the effects of applying such twitches consecutively on airflow dynamics is unknown. The objective of this study was to quantify the effects of five consecutive TMS-induced twitches applied on sleep-induced obstructive hypopnoeic breaths in 10 obstructive sleep apnoea patients. Submental muscle motor threshold (SUBMT) and motor-evoked potential were measured during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, at the beginning of inspiration of consecutive flow-limited respiratory cycles, with the stimulator output set at sleep SUBMT. Maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency and pulse rate variability were assessed. During sleep, SUBMT increased (wakefulness, 25.3 ± 4.9%; NREM sleep, 27.0 ± 6.2%; P = 0.02). During each series of stimulations there was a rise in maximal inspiratory flow (from 306.7 ± 123.2 to 359.8 ± 154.1 ml s(-1); P = 0.0002) and in inspiratory volume (from 346.1 ± 128.1 to 414.9 ± 171.2 ml; P = 0.02) without differences in thoraco-abdominal efforts and inspiratory time. These responses were observed in the absence of arousals and ceased immediately after TMS interruption. Transcranial magnetic stimulation-induced cortical and/or autonomic arousal was observed in 30.2% of all series of stimulation. Consecutive twitch TMS of submental muscles may lead to arousals in a minority of patients but can be applied on consecutive respiratory cycles during sleep and can significantly improve maximal inspiratory flow and inspiratory volume of flow-limited cycles.