Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study.

STUDY OBJECTIVES: Venous blood gases (VBGs) are not consistently considered suitable surrogates for arterial blood gases (ABGs) in assessing acute respiratory failure due to variable measurement error. The physiological stability of patients with chronic ventilatory failure may lead to improved agreement in this setting. METHODS: Adults requiring ABGs for sleep or ventilation titration studies had VBGs drawn before or after each ABG, in a randomized order. Veno-arterial correlation and agreement were examined for carbon dioxide tension (PCO2), pH, oxygen tension (PO2) and oxygen saturation (SO2). RESULTS: We analyzed 115 VBG-ABG pairs from 61 patients. Arterial and venous measures were correlated (with p<0.05) for PCO2 (r=0.84) and pH (r=0.72), but not for PO2 or SO2. Adjusted mean veno-arterial differences (95% limits of agreement) were +5.0mmHg (-4.4 to +14.4) for PCO2; -0.02 (-0.09 to +0.04) for pH; -34.3mmHg (-78.5 to +10.0) for PO2; and -23.9% (-61.3 to +13.5) for SO2. VBGs obtained from the dorsal hand demonstrated a lower mean PCO2 veno-arterial difference (p<0.01). A venous PCO2 threshold of ≥45.8mmHg was >95% sensitive for arterial hypercapnia, so measurements below this can exclude the diagnosis without an ABG. A venous PCO2 threshold of ≥53.7mmHg was >95% specific for arterial hypercapnia, so such readings can be assumed diagnostic. The area under the receiver operating characteristic curve of 0.91 indicated high discriminatory capacity. CONCLUSIONS: A venous PCO2 <45.8mmHg or ≥53.7mmHg would exclude or diagnose hypercapnia, respectively, in patients referred for sleep studies, but VBGs are poor surrogates for ABGs where precision is important. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Register; Name: A comparison of arterial and blood gas analyses in sleep studies; Identifier: ACTRN12617000562370; URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372717.

Mechanisms underlying the prolonged activation of the genioglossus following arousal from sleep.

STUDY OBJECTIVES: Transient arousal from sleep has been shown to elicit a prolonged increase in genioglossus muscle activity that persists following the return to sleep and which may protect against subsequent airway collapse. We hypothesized that this increased genioglossal activity following return to sleep after an arousal is due to persistent firing of inspiratory-modulated motor units (MUs) that are recruited during the arousal. METHODS: Thirty-four healthy participants were studied overnight while wearing a nasal mask with pneumotachograph to measure ventilation and with 4 intramuscular genioglossus EMG electrodes. During stable N2 and N3 sleep, auditory tones were played to induce brief (3-15s) AASM arousals. Ventilation and genioglossus MUs were quantified before the tone, during the arousal and for 10 breaths after the return to sleep. RESULTS: A total of 1089 auditory tones were played and gave rise to 239 MUs recorded across arousal and the return to sleep in 20 participants (aged 23 ±â€…4.2 years and BMI 22.5 ±â€…2.2 kg/m2). Ventilation was elevated above baseline during arousal and the first post-arousal breath (p < .001). Genioglossal activity was elevated for five breaths following the return to sleep, due to increased firing rate and recruitment of inspiratory modulated MUs, as well as a small increase in tonic MU firing frequency. CONCLUSIONS: The sustained increase in genioglossal activity that occurs on return to sleep after arousal is primarily a result of persistent activity of inspiratory-modulated MUs, with a slight contribution from tonic units. Harnessing genioglossal activation following arousal may potentially be useful for preventing obstructive respiratory events.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-ß (Aß) burden, the hallmark of Alzheimer's disease, and cognitive decline. OBJECTIVE: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. METHODS: Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aß burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. RESULTS: Aß burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aß burden when controlling for sleep variables. CONCLUSIONS: Nocturnal hypoxemia was related to brain Aß burden in this sample of OSA participants. Aß burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aß burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether it may be a therapeutic target for dementia prevention in OSA is yet to be determined.

The influence of alcohol on genioglossus single motor units in men and women during wakefulness.

NEW FINDINGS: What is the central question of this study? How does alcohol intake, which worsens obstructive sleep apnoea, alter motor control of the genioglossus muscle, an upper airway dilator, in healthy awake human volunteers, and does alcohol alter genioglossus muscle afterdischarge? What is the main finding and its importance? Alcohol consumption had a very minor effect on the activity of the genioglossus in healthy young individuals studied during wakefulness and did not alter afterdischarge, leaving open the possibility that alcohol worsens obstructive sleep apnoea via other mechanisms. ABSTRACT: Alcohol worsens obstructive sleep apnoea (OSA). This effect is thought to be due to alcohol's depressant effect on upper airway dilator muscles such as the genioglossus, but how alcohol reduces genioglossal activity is unknown. The aim of this study was to investigate the effect of alcohol consumption on genioglossus muscle single motor units (MUs). Sixteen healthy individuals were studied on two occasions (alcohol: breath alcohol concentration ∼0.07% and placebo). They were instrumented with a nasal mask, four intramuscular genioglossal EMG electrodes, and an ear oximeter. They were exposed to 8-12 hypoxia trials (45-60 s of 10% O2 followed by one breath of 100% O2 ) while awake. MUs were sorted according to their firing patterns and quantified during baseline, hypoxia and recovery. For the alcohol and placebo conditions, global muscle activity (mean ± SD peak inspiratory EMG = 119.3 ± 44.1 and 126.5 ± 51.9 µV, respectively, P = 0.53) and total number of MUs recorded at baseline (68 and 67, respectively) were similar. Likewise, the peak discharge frequency did not differ between conditions (21.2 ± 4.28 vs. 22.4 ± 4.08 Hz, P = 0.09). There was no difference between conditions in the number (101 vs. 88, respectively) and distribution of MU classes during hypoxia, and afterdischarge duration was also similar. In this study, alcohol had a very minor effect on genioglossal activity and afterdischarge in these otherwise healthy young individuals studied while awake. If similar effects are observed during sleep, it would suggest that the worsening of OSA following alcohol may be related to increased upper airway resistance/nasal congestion or arousal threshold changes.

Sleep-disordered breathing was associated with lower health-related quality of life and cognitive function in a cross-sectional study of older adults.

BACKGROUND AND OBJECTIVE: The clinical significance of sleep-disordered breathing (SDB) in older age is uncertain. This study determined the prevalence and associations of SDB with mood, daytime sleepiness, quality of life (QOL) and cognition in a relatively healthy older Australian cohort. METHODS: A cross-sectional analysis was conducted from the Study of Neurocognitive Outcomes, Radiological and retinal Effects of Aspirin in Sleep Apnoea. Participants completed an unattended limited channel sleep study to measure the oxygen desaturation index (ODI) to define mild (ODI 5-15) and moderate/severe (ODI ≥ 15) SDB, the Centre for Epidemiological Studies Scale, the Epworth Sleepiness Scale, the 12-item Short-Form for QOL and neuropsychological tests. RESULTS: Of the 1399 participants (mean age 74.0 years), 36% (273 of 753) of men and 25% (164 of 646) of women had moderate/severe SDB. SDB was associated with lower physical health-related QOL (mild SDB: beta coefficient [ß] -2.5, 95% CI -3.6 to -1.3, p < 0.001; moderate/severe SDB: ß -1.8, 95% CI -3.0 to -0.6, p = 0.005) and with lower global composite cognition (mild SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.022; moderate/severe SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.032) compared to no SDB. SDB was not associated with daytime sleepiness nor depression. CONCLUSION: SDB was associated with lower physical health-related quality of life and cognitive function. Given the high prevalence of SDB in older age, assessing QOL and cognition may better delineate subgroups requiring further management, and provide useful treatment target measures for this age group.

Exclusion of EEG-based arousals in wake epochs of polysomnography leads to underestimation of the arousal index.

STUDY OBJECTIVES: There is an internal contradiction in current American Academy of Sleep Medicine standards for arousal index (AI) calculation in polysomnography: Arousals in sleep and wake epochs are counted, but only sleep time is used in the denominator. This study aimed to investigate the impact of including arousals scored in wake epochs on the AI. METHODS: We compared AIs including (AIinc) vs excluding (AIexc) awake-epoch arousals from 100 consecutive polysomnograms conducted for investigation of possible obstructive sleep apnea. To determine the AI that most closely approximated "truth," AIinc and AIexc were compared to an AI calculated from continuous sleep analysis (AIcont) in a 20-polysomnogram subgroup of patients. RESULTS: The median (interquartile range) increase in AIinc was 5.2 events/h (3.5-8.1) vs AIexc (AIinc = 28.0 events/h [18.4-38.9] vs AIexc = 22.9 events/ h [13.1-31.3]), equating to an increase of 25.3% (15.6-40.8). As the AI increased, the difference increased (P < .001), with decreasing sleep efficiency and an increasing apnea-hypopnea index as the strongest predictors of the difference between AIexc and AIinc. The absolute AIexc-AIcont difference (7.7 events/h [5.1-13.6]) was significantly greater than the AIinc-AIcont difference (1.2 events/h [0.6-5.7]; z = -3.099; P = .002). CONCLUSIONS: There was a notable increase in AI when we included wake-epoch arousals, particularly in patients with more severe obstructive sleep apnea or reduced sleep efficiency. However, the AI including wake-epoch arousals best matched the "true" continuous sleep-scoring AI. Our study informs clinical and research practice, highlights epoch scoring pitfalls, and supports the current American Academy of Sleep Medicine standard arousal reporting approach for future standards. CITATION: Wilson DL, Tolson J, Churchward TJ, Melehan K, O'Donoghue FJ, Ruehland WR. Exclusion of EEG-based arousals in wake epochs of polysomnography leads to underestimation of the arousal index. J Clin Sleep Med. 2022;18(5):1385-1393.

Tetraplegic obstructive sleep apnoea patients dilate the airway similarly to able-bodied obstructive sleep apnoea patients.

Context/objective: Obstructive sleep apnoea (OSA) develops soon after cervical spinal cord injury (SCI) at rates higher than the general population, but the mechanisms are not understood. This study aimed to determine whether OSA in SCI is associated with altered pharyngeal muscle dilatory mechanics during quiet breathing, as has been observed in the non-SCI injured with obstructive sleep apnoea.Design: Cross sectional imaging study.Setting: Medical research institute.Participants: Eight cervical SCI patients with OSA were recruited and compared to 13 able-bodied OSA patients and 12 able-bodied healthy controls of similar age and BMI.Interventions and outcome measures: 3T MRI scans of upper airway anatomy and tagged-MRI to characterize airway muscle motion during quiet breathing were collected for analysis.Results: Considerable variation in the patterns of inspiratory airway muscle motion was observed in the SCI group, with some participants exhibiting large inspiratory airway dilatory motions, and others exhibiting counterproductive narrowing during inspiration. These patterns were not dissimilar to those observed in the able-bodied OSA participants. The increase in airway cross-sectional area of able-bodied control participants was proportional to increase in BMI, and a similar, but not significant, relationship was present in all groups.Conclusion: Despite the limited sample size, these data suggest that SCI OSA patients have heterogeneous pharyngeal dilator muscle responses to the negative pressures occurring during inspiration but, as a group, appear to be more similar to able-bodied OSA patients than healthy controls of similar age and BMI. This may reflect altered pharyngeal pressure reflex responses in at least some people with SCI.

Eye blink parameters to indicate drowsiness during naturalistic driving in participants with obstructive sleep apnea: A pilot study.

OBJECTIVES: To determine whether continuous eye blink measures could identify drowsiness in patients with obstructive sleep apnea (OSA) during a week of naturalistic driving. DESIGN: Observational study comparing OSA patients and healthy controls. SETTING: Regular naturalistic driving across one week. PARTICIPANTS: Fifteen untreated moderate to severe OSA patients and 15 age (± 5 years) and sex (female = 6) matched healthy controls. MEASUREMENTS: Participants wore an eye blink drowsiness recording device during their regular driving for one week. RESULTS: During regular driving, the duration of time with no ocular movements (quiescence), was elevated in the OSA group by 43% relative to the control group (mean [95% CI] 0.20[0.17, 0.25] vs 0.14[0.12, 0.18] secs, P = .011). During long drives only, the Johns Drowsiness Scale was also elevated and increased by 62% in the OSA group relative to the control group (1.05 [0.76, 1.33] vs 0.65 [0.36, 0.93], P = .0495). Across all drives, critical drowsiness events (defined by a Johns Drowsiness Scale score ≥2.6) were twice as frequent in the OSA group than the control group (rate ratio [95% CI] =1.93 [1.65, 2.25], P ≤ .001). CONCLUSIONS: OSA patients were drowsier than healthy controls according to some of the continuous real time eye blink drowsiness measures. The findings of this pilot study suggest that there is potential for eye blink measures to be utilized to assess fitness to drive in OSA patients. Future work should assess larger samples, as well as the relationship of eye blink measures to conventional fitness to drive assessments and crash risk.

After-discharge in the upper airway muscle genioglossus following brief hypoxia.

STUDY OBJECTIVES: Genioglossus (GG) after-discharge is thought to protect against pharyngeal collapse by minimizing periods of low upper airway muscle activity. How GG after-discharge occurs and which single motor units (SMUs) are responsible for the phenomenon are unknown. The aim of this study was to investigate genioglossal after-discharge. METHODS: During wakefulness, after-discharge was elicited 8-12 times in healthy individuals with brief isocapnic hypoxia (45-60 s of 10% O2 in N2) terminated by a single breath of 100% O2. GG SMUs were designated as firing solely, or at increased rate, during inspiration (Inspiratory phasic [IP] and inspiratory tonic [IT], respectively); solely, or at increased rate, during expiration (Expiratory phasic [EP] or expiratory tonic [ET], respectively) or firing constantly without respiratory modulation (Tonic). SMUs were quantified at baseline, the end of hypoxia, the hyperoxic breath, and the following eight normoxic breaths. RESULTS: A total of 210 SMUs were identified in 17 participants. GG muscle activity was elevated above baseline for seven breaths after hyperoxia (p < 0.001), indicating a strong after-discharge effect. After-discharge occurred due to persistent firing of IP and IT units that were recruited during hypoxia, with minimal changes in ET, EP, or Tonic SMUs. The firing frequency of units that were already active changed minimally during hypoxia or the afterdischarge period (p > 0.05). CONCLUSION: That genioglossal after-discharge is almost entirely due to persistent firing of previously silent inspiratory SMUs provides insight into the mechanisms responsible for the phenomenon and supports the hypothesis that the inspiratory and expiratory/tonic motor units within the muscle have idiosyncratic functions.

Severe Obstructive Sleep Apnea Is Associated with Higher Brain Amyloid Burden: A Preliminary PET Imaging Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to an increase risk of dementia. Few studies have cross-sectionally examined whether clinically-confirmed OSA is associated with a higher brain amyloid burden. OBJECTIVE: The aim of this study was to compare brain amyloid burden in individuals with untreated OSA and healthy controls, and explore associations between amyloid burden and polysomnographic and subjective measures of sleep, demographics, and mood. METHODS: Thirty-four individuals with OSA (mean age 57.5±4.1 y; 19 males) and 12 controls (mean age 58.5±4.2 y; 6 males) underwent a clinical polysomnogram and a 11C-PiB positron emission tomography (PET) scan to quantify amyloid burden. RESULTS: Amyloid burden was elevated in the OSA group relative to controls, and was significantly higher in those with severe OSA relative to mild/moderate OSA. Correlation analyses indicated that higher amyloid burden was associated with a higher Non-REM apnea hypopnea index, poorer sleep efficiency, and less time spent in stage N3 sleep, when controlling for age. CONCLUSION: Severe OSA is associated with a modest elevation of brain amyloid, the significance of which should be further investigated to explore the implications for dementia risk.

Does Nasal Obstruction Induce Obstructive Sleep Apnea in Healthy Women?

PURPOSE: Obstructive sleep apnea (OSA) is less prevalent among women and is associated with different symptoms and consequences to OSA in men. The reasons for these differences are unknown and difficult to tease apart in clinical populations. If OSA could be temporarily induced in healthy men and women, the causes of some of these differences could be investigated. Nasal blocking has been used to induce OSA in healthy men but its effect in women has not been reported. PATIENTS AND METHODS: A total of 14 healthy individuals (10 women) underwent in-laboratory diagnostic sleep studies on two occasions separated by a week. On one occasion, the nasal passages were blocked, whereas on the other occasion, participants slept naturally. In both conditions, a full-face mask was used to monitor respiratory events. Participants' self-reported sleepiness, mood and performance on a motor learning task were assessed in the evening and morning of both sleep studies. Furthermore, endothelial function and self-reported sleep quality were assessed in the morning following each study. RESULTS: Nasal blockage induced OSA in healthy young (age=22±3 years) and slim (BMI=22.2±3.2 kg/m2) women (control AHI=2.0±2.6, blocked AHI=33.1±36.7 events/hr, p=0.02). One night of OSA was associated with poorer self-reported sleep quality (p<0.001) and increased self-reported snoring (p<0.04), choking and gasping during sleep (p<0.001) but was not associated with alterations in mood, neurocognitive or endothelial function on the following morning. CONCLUSION: Nasal blockage induces OSA in healthy, young, and normal weight women. However, whether the induced OSA is representative of naturally occurring OSA and the technique useful for future studies is unclear.

Integrity of Multiple Memory Systems in Individuals With Untreated Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with working- and autobiographical-memory impairments, and high rates of mood disorder. This study aimed to examine (i) behavioral responses and (ii) neural activation patterns elicited by autobiographical and working memory tasks in moderate-severe untreated OSA patients and healthy controls, and (iii) whether variability in autobiographical and working memory activation are associated with task performance, OSA severity and psychological symptomatology (depression, anxiety). In order to control for the potential confounding effect of elevated rates of clinical depression in OSA, we excluded individuals with a current psychiatric condition. Seventeen untreated OSA participants and 16 healthy controls were comparable with regards to both activation and behavioral performance. OSA was associated with worse subclinical mood symptoms and poorer personal semantic memory. Higher levels of nocturnal hypoxia were associated with increased activation in the occipital cortex and right cerebellum during the working memory task in OSA participants, however, no significant relationships between activation and task performance or depressive/anxiety symptomatology were observed. The neurocognitive substrates supporting autobiographical recall of recent events and working memory in younger, recently diagnosed individuals with OSA appear to be indistinguishable from healthy age-matched individuals. These findings point to the importance of early diagnosis and treatment of OSA in order to preserve cognitive function.

Sleep-disordered breathing does not impact maternal outcomes in women with hypertensive disorders of pregnancy.

OBJECTIVE: Sleep-disordered breathing (SDB) is characterised by intermittent hypoxemia, sympathetic activation and widespread endothelial dysfunction, sharing pathophysiologic features with the hypertensive disorders of pregnancy. We sought to determine whether coexisting SDB would adversely impact the outcomes of women with gestational hypertension (GH) and preeclampsia (PE), and healthy matched controls. STUDY DESIGN: Women diagnosed with GH or PE along with BMI- and gestation-matched normotensive controls underwent polysomnography in late pregnancy to establish the presence or absence of SDB (RDI ≥ 5). Clinical outcomes of hypertensive disease severity were compared between groups, and venous blood samples were taken in the third trimester and at delivery to examine for any impact of SDB on the anti-angiogenic markers of PE. RESULTS: Data was available for 17 women with PE, 24 women with GH and 44 controls. SDB was diagnosed in 41% of the PE group, 63% of the GH group and 39% of the control group. Women with PE and co-existing SDB did not have worse outcomes in terms of gestation at diagnosis of PE (SDB = 29.1 (25.9, 32.1) weeks vs. no SDB = 32.0 (29.0, 33.9), p = n.s.) and days between diagnosis of PE and delivery (SDB = 20.0 (4.0, 35.0) days vs. no SDB = 10.5 (9.0, 14.0), p = n.s.). There were also no differences in severity of hypertension, antihypertensive treatment and biochemical, haematological and anti-angiogenic markers of PE between SDB and no SDB groups. Similar results were observed among women with GH. Healthy control women with SDB were no more likely to develop a hypertensive disorder of pregnancy in the later stages of pregnancy (SDB = 5.9% vs. no SDB = 7.4%, p = n.s.). Increasing the threshold for diagnosis of SDB to RDI ≥ 15 did not unmask a worse prognosis. CONCLUSION: The presence of SDB during pregnancy did not worsen the disease course of GH or PE, and was not associated with high blood pressure or anti-angiogenic markers of hypertensive disease amongst healthy pregnant women. Given the numerous reports of the relationship between SDB and diagnosis of hypertensive disorders of pregnancy, it appears more work is required to distinguish causal, versus confounding, pathways.

The presence of coexisting sleep-disordered breathing among women with hypertensive disorders of pregnancy does not worsen perinatal outcome.

OBJECTIVE: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. STUDY DESIGN: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. RESULTS: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p = .19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group-SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group-SDB = 41.7% vs. No SDB = 25.0%, p = .44), nor did SDB affect the total number of decelerations overnight (HDP group-SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p = .94; control group-SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26-22.26), p = .02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p = .015) and fewer growth restricted babies at birth (30% vs. 68.4%, p = .026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. CONCLUSION: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease.

Genioglossus muscle responses to resistive loads in severe OSA patients and healthy control subjects.

This study aimed to determine whether there is impairment of genioglossus neuromuscular responses to small negative pressure respiratory stimuli, close to the conscious detection threshold, in obstructive sleep apnea (OSA). We compared genioglossus electromyogram (EMGgg) responses to midinspiratory resistive loads of varying intensity (≈1.2-6.2 cmH2O·L-1·s), delivered via a nasal mask, between 16 severe OSA and 17 control participants while the subjects were awake and in a seated upright position. We examined the relationship between stimulus intensity and peak EMGgg amplitude in a 200-ms poststimulus window and hypothesized that OSA patients would have an increased activation threshold and reduced sensitivity in the relationship between EMGgg activation and stimulus intensity. There was no significant difference between control and OSA participants in the threshold (P = 0.545) or the sensitivity (P = 0.482) of the EMGgg amplitude vs. stimulus intensity relationship, where change in epiglottic pressure relative to background epiglottic pressure represented stimulus intensity. These results do not support the hypothesis that deficits in neuromuscular response to negative upper airway pressure exist in OSA during wakefulness; however, the results are likely influenced by a counterintuitive and novel genioglossus muscle suppression response observed in a significant proportion of both OSA and healthy control participants. This suppression response may relate to the inhibition seen in inspiratory muscles such as the diaphragm in response to sudden-onset negative pressure, and its presence provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.NEW & NOTEWORTHY Our study used a novel midinspiratory resistive load stimulus to study upper airway neuromuscular responses to negative pressure during wakefulness in obstructive sleep apnea (OSA). Although no differences were found between OSA and healthy groups, the study uncovered a novel and unexpected suppression of neuromuscular activity in a large proportion of both OSA and healthy participants. The unusual response provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.

The effect of sex and body weight on lung volumes during sleep.

STUDY OBJECTIVES: Low lung volumes are thought to contribute to obstructive sleep apnea (OSA). OSA is worse in the supine versus lateral body position, men versus women, obese versus normal-weight (NW) individuals and REM versus NREM sleep. All of these conditions may be associated with low lung volumes. The aim was to measure FRC during wake, NREM, and REM in NW and overweight (OW) men and women while in the supine and lateral body positions. METHODS: Eighty-one healthy adults were instrumented for polysomnography, but with nasal pressure replaced with a sealed, non-vented mask connected to an N2 washout system. During wakefulness and sleep, repeated measurements of FRC were made in both supine and right lateral positions. RESULTS: Two hundred eighty-five FRC measures were obtained during sleep in 29 NW (body mass index [BMI] = 22 ± 0.3 kg/m2) and 29 OW (BMI = 29 ± 0.7 kg/m2) individuals. During wakefulness, FRC differed between BMI groups and positions (supine: OW = 58 ± 3 and NW = 68 ± 3% predicted; lateral OW = 71 ± 3, NW = 81 ± 3% predicted). FRC fell from wake to NREM sleep in all participants and in both positions by a similar amount. As a result, during NREM sleep FRC was lower in OW than NW individuals (supine 46 ± 3 and 56 ± 3% predicted, respectively). FRC during REM was similar to NREM and no sex differences were observed in any position or sleep stage. CONCLUSIONS: Reductions in FRC while supine and with increased body weight may contribute to worsened OSA in these conditions, but low lung volumes appear unlikely to explain the worsening of OSA in REM and in men versus women.

Randomised controlled trial of polysomnographic titration of noninvasive ventilation.

Noninvasive ventilation (NIV) settings determined during wakefulness may produce patient-ventilator asynchrony (PVA) during sleep, causing sleep disruption and limiting tolerance. This study investigated whether NIV titrated with polysomnography (PSG) is associated with less PVA and sleep disruption than therapy titrated during daytime alone.Treatment-naive individuals referred for NIV were randomised to control (daytime titration followed by sham polysomnographic titration) or PSG (daytime titration followed by polysomnographic titration) groups. Primary outcomes were PVA and arousal indices on PSG at 10 weeks. Secondary outcomes included adherence, gas exchange, symptoms and health-related quality of life (HRQoL).In total, 60 participants were randomised. Most (88.3%) had a neuromuscular disorder and respiratory muscle weakness but minor derangements in daytime arterial blood gases. PVA events were less frequent in those undergoing polysomnographic titration (median (interquartile range (IQR)): PSG 25.7 (12-68) events·h-1 versus control 41.0 (28-182) events·h-1; p=0.046), but arousals were not significantly different (median (IQR): PSG 11.4 (9-19) arousals·h-1 versus control 14.6 (11-19) arousals·h-1; p=0.258). Overall adherence was not different except in those with poor early adherence (<4 h·day-1) who increased their use after polysomnographic titration (mean difference: PSG 95 (95% CI 29-161) min·day-1 versus control -23 (95% CI -86-39) min·day-1; p=0.01). Arterial carbon dioxide tension, somnolence and sleep quality improved in both groups. There were no differences in nocturnal gas exchange or overall measures of HRQoL.NIV titrated with PSG is associated with less PVA but not less sleep disruption when compared with therapy titrated during daytime alone.

Evidence against a subcortical gate preventing conscious detection of respiratory load stimuli.

Respiratory related evoked potentials (RREP) were used to examine respiratory stimulus gating. RREPs produced by consciously detected vs. undetected loads, near the detection threshold, were compared. Participants (n = 17) were instrumented with EEG and a nasal mask connected to a loading manifold, which presented a range of mid-inspiratory resistive loads, plus a control, in a random block design. Participants were cued prior to the stimulus and signalled detection by a button press. There were statistically significant differences in peak-to-peak amplitude of the P1 RREP peak for detected (mean ± SD; 3.86 ± 1.45 µV; P = 0.020) and undetected loads (3.67 ± 1.27 µV; P = 0.002) vs. control (2.36 ± 0.81 µV), although baseline-to-peak differences were not significantly different. In contrast peak-to-peak P3 amplitude was significantly greater for detected (5.91 ± 1.54 µV; P < 0.001) but not undetected loads (3.33 ± 0.98 µV; P = 0.189) vs. control (3.69 ± 1.46 µV), with the same pattern observed for baseline-to-peak measurements. The P1 peak, thought to reflect arrival of somatosensory information, appeared to be present in response to both detected and undetected loads, but the later P3 peak, was present for detected loads only. This suggests that for sub-threshold loads sensory information may reach the cortex, arguing against a sub-cortical gating process.

Sleeping tongue: current perspectives of genioglossus control in healthy individuals and patients with obstructive sleep apnea.

The focus of this review was on the genioglossus (GG) muscle and its role in maintaining upper airway patency in both healthy individuals and obstructive sleep apnea (OSA) patients. This review provided an overview of GG anatomy and GG control and function during both wakefulness and sleep in healthy individuals and in those with OSA. We reviewed evidence for the role of the GG in OSA pathogenesis and also highlighted abnormalities in GG morphology, responsiveness, tissue movement patterns and neurogenic control that may contribute to or result from OSA. We summarized the different methods for improving GG function and/or activity in OSA and their efficacy. In addition, we discussed the possibility that assessing the synergistic activation of multiple upper airway dilator muscles may provide greater insight into upper airway function and OSA pathogenesis, rather than assessing the GG in isolation.