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BACKGROUND Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P

BACKGROUND The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4-mg reboxetine plus 5-mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.

RATIONALE: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. OBJECTIVES: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). METHODS: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory “drive” (calibrated intraesophageal diaphragm EMG), ventilation (oronasal “ventilation”), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation–drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. MEASUREMENTS AND MAIN RESULTS: REM sleep (⩾10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], −21.8% [−31.2% to −12.4%] of eupnea; P

Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypo...

Rationale: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea–hypopnea index (AHI). Respiratory event duration is a he...

Rationale: Mandibular advancement device (MAD) treatment efficacy varies among patients with obstructive sleep apnea. Objectives: The current study aims to explain underlying individual differences in efficacy using obstructive sleep apnea endotypic traits calculated from baseline clinical polysomnography: collapsibility (airflow at normal ventilatory drive), loop gain (drive response to reduced airflow), arousal threshold (drive preceding arousal), compensation (increase in airflow as drive increases), and the ventilatory response to arousal (increase in drive explained by arousal). On the basis of previous research, we hypothesized that responders to MAD treatment have a lower loop gain and milder collapsibility. Methods: Thirty-six patients (median apnea–hypopnea index [AHI], 23.5 [interquartile range (IQR), 19.7–29.8] events/h) underwent baseline and 3-month follow-up full polysomnography, with MAD fixed at 75% of maximal protrusion. Traits were estimated using baseline polysomnography according to Sands and colleagues. Response was defined as an AHI reduction ≥ 50%. Results: MAD treatment significantly reduced AHI (49.7%(baseline) [23.9–63.6], median [IQR]). Responders exhibited lower loop gain (mean [95% confidence interval], 0.53 [0.48–0.58] vs. 0.65 [0.57–0.73]; P = 0.020) at baseline than nonresponders, a difference that persisted after adjustment for baseline AHI and body mass index. Elevated loop gain remained associated with nonresponse after adjustment for collapsibility (odds ratio, 3.03 [1.16–7.88] per 1–standard deviation (SD) increase in loop gain [SD, 0.15]; P = 0.023). Conclusions: MAD nonresponders exhibit greater ventilatory instability, expressed as higher loop gain. Assessment of the baseline degree of ventilatory instability using this approach may improve upfront MAD treatment patient selection. Clinical trial registered with www.clinicaltrials.gov (NCT 01532050)

Background Heart failure (HF) is a leading cause of morbidity and mortality and although it is linked to sleep apnea, which physiological stressors most strongly associate with incident disease is unclear. We tested whether sleep apnea-specific hypoxic burden (SASHB) predicts incident HF in two independent cohort studies. Research Question In comparison with apnea-hypopnea index (AHI), how does sleep apnea-specific hypoxic burden predict incident HF? Study Design and Methods The samples were derived from two cohort studies: The Sleep Heart Health Study (SHHS), which included 4,881 middle-aged and older adults (54.4% women), age 63.6 ± 11.1 years; and the Outcomes of Sleep Disorders in Older Men (MrOS), which included 2,653 men, age 76.2 ± 5.4 years. We computed SASHB as the sleep apnea-specific area under the desaturation curve from pre-event baseline. We used Cox models for incident HF to estimate the adjusted hazard ratios (HRs) for natural log-transformed SASHB and AHI adjusting for multiple confounders. Results The SASHB predicted incident HF in men in both cohorts, whereas AHI did not. Men in SHHS and MrOS had adjusted HRs (per 1SD increase in SASHB) of 1.18 (95% CI, 1.02-1.37) and 1.22 (95% CI, 1.02-1.45), respectively. Associations with SASHB were observed in men with both low and high AHI levels. Associations were not significant in women. Interpretation In men, the hypoxic burden of sleep apnea was associated with incident HF after accounting for demographic factors, smoking, and co-morbidities. The findings Suggest that quantification of an easily measured index of sleep apnea-related hypoxias may be useful for identifying individuals at risk for heart disease, while also suggesting targets for intervention.

Background & Aims: With the advancement of science and technology in the current era, cancer in adolescents is not as deadly as before and has only become a chronic disease with a higher survival rate. Despite the advances in cancer treatment and care, the disease is still associated with severe psychological consequences. The impact of cancer on various dimensions of adolescentschr('39') life (especially psychological dimensions) necessitates interventions to foster adaptation in the psychosocial dimension. Adolescents with cancer use a variety of social support resources to deal with the diagnosis and treatment of their disease. Family plays a pivotal role in providing the emotional and social support to these patients, and the perception of family support is considered to be the most important facilitator of health behavior, as well as the most potent strategy to successfully deal with stressors. It seems that the provision of emotional support by the family to adolescents with cancer helps these patients rely on the family and feel confident in coping with their difficult and critical condition, refrain from isolation, and feel encouraged. The present study aimed to evaluate the correlations between perceived family support and psychosocial adjustment with the disease in adolescents with cancer. Materials & Methods: This descriptive-correlational study was conducted based on the error level of α=0.05 with 80% test power and sample size of 85. Considering 10% attrition, 95 adolescents aged 11-20 years diagnosed with cancer, who referred to two hospitals affiliated to Shiraz University of Medical Sciences in 2019, were selected via convenience sampling. Data were collected using a questionnaire containing three sections of demographic characteristics, perceived family support questionnaire, and psychosocial adjustment questionnaire during July-November 2019. Data analysis was performed in SPSS version 16 using descriptive and analytical statistics at the significance level of P

The deregulation of microRNAs (miRs) has been identified in tumor development. Indeed, the restoration of tumor-suppressive miRs has been associated with inhibited tumor development in various cancers. Herein, we aimed to evaluate the impact of combined miR-383-5p restoration, as a tumor-suppressive miR, with taxol therapy in suppressing MDA-MB-231 breast cancer development. MDA-MB-231 cell line was restored with miR-383-5p and treated with paclitaxel both in combined and separate manners. The MTT experiment was carried out to measure the cytotoxicity of the therapeutic approaches on the tumoral cells. Besides, flow cytometry was conducted to assess apoptosis and cell cycle status following the treatments. Furthermore, the expression levels of critical factors contributed to tumor proliferation, migration, apoptosis were investigated via the qRT-PCR and western blotting techniques. The outcomes pointed out that the miR-383-5p might substantially enhance the chemosensitivity of MDA-MB-231 to taxol. Besides, miR-383-5p restoration and the combined therapy of miR-383-5p restoration with paclitaxel could remarkably increase apoptosis, decrease cell viability, arrest the cell cycle, inhibit clonogenicity, suppress tumor migration, suppress the PI3K/Akt signaling pathway, and down-regulate PD-L1 expression of BC cells. The restoration of miR-383-5p can enhance the chemosensitivity of MDA-MB-231 cells to taxol. Despite the anti-tumoral effects of miR-383-5p restoration on MDA-MB-231 breast cancer development, the combined therapy of miR-383-5p restoration with paclitaxel can be more effective in repressing MDA-MB-231 breast cancer development.

Study Objectives The presence of flow limitation during sleep is associated with adverse health consequences independent of obstructive sleep apnea (OSA) severity (apnea-hypopnea index, AHI), but remains extremely challenging to quantify. Here we present a unique library and an accompanying automated method that we apply to investigate flow limitation during sleep. Methods A library of 117,871 breaths (N = 40 participants) were visually classified (certain flow limitation, possible flow limitation, normal) using airflow shape and physiological signals (ventilatory drive per intra-esophageal diaphragm EMG). An ordinal regression model was developed to quantify flow limitation certainty using flow-shape features (e.g. flattening, scooping); breath-by-breath agreement (Cohen’s ƙ); and overnight flow limitation frequency (R2, %breaths in certain or possible categories during sleep) were compared against visual scoring. Subsequent application examined flow limitation frequency during arousals and stable breathing, and associations with ventilatory drive. Results The model (23 features) assessed flow limitation with good agreement (breath-by-breath ƙ = 0.572, p < 0.001) and minimal error (overnight flow limitation frequency R2 = 0.86, error = 7.2%). Flow limitation frequency was largely independent of AHI (R2 = 0.16) and varied widely within individuals with OSA (74[32–95]%breaths, mean[range], AHI > 15/h, N = 22). Flow limitation was unexpectedly frequent but variable during arousals (40[5–85]%breaths) and stable breathing (58[12–91]%breaths), and was associated with elevated ventilatory drive (R2 = 0.26–0.29; R2 < 0.01 AHI v. drive). Conclusions Our method enables quantification of flow limitation frequency, a key aspect of obstructive sleep-disordered breathing that is independent of the AHI and often unavailable. Flow limitation frequency varies widely between individuals, is prevalent during arousals and stable breathing, and reveals elevated ventilatory drive. Clinical trial registration: The current observational physiology study does not qualify as a clinical trial.

Study Objectives New electroencephalogram (EEG) features became available for use in polysomnography and have shown promise in early studies. They include a continuous index of sleep depth (odds-ratio-product: ORP), agreement between right and left sleep depth (R/L coefficient), dynamics of sleep recovery following arousals (ORP-9), general EEG amplification (EEG Power), alpha intrusion and arousal intensity. This study was undertaken to establish ranges and reproducibility of these features in subjects with different demographics and clinical status. Methods We utilized data from the two phases of the Sleep-Heart-Health-Study (SHHS1 and SHHS2). Polysomnograms of 5,804 subjects from SHHS1 were scored to determine the above features. Feature values were segregated according to clinical status of obstructive sleep apnea (OSA), insomnia, insomnia plus OSA, no clinical sleep disorder, and demographics (age, gender, and race). Results from SHHS visit2 were compared with SHHS1 results. Results All features varied widely among clinical groups and demographics. Relative to participants with no sleep disorder, wake ORP was higher in participants reporting insomnia symptoms and lower in those with OSA (p < 0.0001 for both), reflecting opposite changes in sleep pressure, while NREM ORP was higher in both insomnia and OSA (p 0.75). Conclusions The reported results serve as bases for interpreting studies that utilize novel sleep EEG biomarkers and identify characteristic EEG changes that vary with age, gender and may help distinguish insomnia from OSA.

Citation:Azarbarzin A, White DP. Reply to “Impact of obstructive sleep apnea on left ventricular mass index in men with coronary artery disease.” J Clin Sleep Med. 2021;17(2):357.

BACKGROUND: Conventional metrics to evaluate sleep-disordered breathing (SDB) have many limitations, including their inability to identify subclinical markers of cardiovascular (CV) dysfunction. RESEARCH QUESTION: Does sleep study-derived circulation time (Ct) predict mortality, independent of CV risks and SDB severity? STUDY DESIGN AND METHODS: We derived average lung to finger Ct (LFCt) from sleep studies in older men enrolled in the multicenter Osteoporotic Fractures in Men (MrOS) Sleep study. LFCt was defined as the average time between end of scored respiratory events and nadir oxygen desaturations associated with those events. We calculated the hazard ratio (HRs) for the CV and all-cause mortality by LFCt quartiles, adjusting for the demographic characteristics, body habitus, baseline CV risk, and CV disease (CVD). Additional models included apnea-hypopnea index (AHI), time with oxygen saturation as measured by pulse oximetry (SpO(2)) < 90% (T90), and hypoxic burden. We also repeated analyses after excluding those with CVD at baseline. RESULTS: A total of 2,631 men (mean ± SD age, 76.4 ± 5.5 years) were included in this study. LFCt median (interquartile range) was 18 (15-22) s. During an average ± SD follow-up of 9.9 ± 3.5 years, 427 men (16%) and 1,205 men (46%) experienced CV death and all-cause death, respectively. In multivariate analysis, men in the fourth quartile of LFCt (22-52 s) had an HR of 1.36 (95% CI, 1.02-1.81) and 1.35 (95% CI, 1.14-1.60) for CV and all-cause mortality, respectively, when compared with men in the first quartile (4-15 s). The results were similar when additionally adjusting for AHI, T90, or hypoxic burden. Results were stronger among men with no history of CVD at baseline. INTERPRETATION: LFCt is associated with both CV and all-cause mortality in older men, independent of baseline CV burden and SDB metrics. LFCt may be a novel physiologic marker for subclinical CVD and adverse outcomes in patients with SDB.

Obstructive sleep apnea is associated with increased risk of car crashes; however, conventional measures of sleep apnea severity do not clearly identify those individuals who are at greatest risk. Here we tested whether, among individuals with sleep apnea, those with reduced interhemispheric sleep depth coherence, measured by correlation between right and left hemisphere odds ratio product, are at greater risk. The sample was derived from the Sleep Heart Health Study, a prospective observational cohort study, and included 1,378 adults with sleep apnea. The occurrence of a car crash was ascertained by a questionnaire administered 2 years after the sleep study, which asked about the occurrence of crashes during the year prior to questionnaire administration. We computed the sleep depth coherence from electroencephalograms recorded during baseline sleep studies and after 5 years. The weighted kappa coefficient and Bangdiwala's B were 0.34 and 0.59, respectively, indicating a fair to moderate stability over a 5-year interval. Multivariate logistic regression, adjusted for age, sex, race, body mass index and miles driven per year, was used to assess the risk of a car crash. Compared to the lowest quartile of sleep depth coherence (0.86), individuals in the highest quartile (0.93) had a 62% (95% confidence interval, 22%-81%) lower risk of an accident. Further adjustments for usual sleep duration and sleepiness did not meaningfully alter these findings. Higher interhemispheric sleep depth coherence is associated with significantly lower risk of motor vehicle crashes in individuals with sleep apnea. This suggests that high interhemispheric sleep depth coherence may be a marker of resistance to sleep apnea-related adverse neurocognitive outcomes.

Since gastric cancer (GC) is diagnosed at advanced stages, the survival rate is low in affected people. In this regard, investigating the mechanisms underlying GC development, are so critical. MiRNAs, which are small non coding RNAs, as a post transcriptional repressor, regulate expression of target genes by stimulating breakage or transcription suppression of their targets therefore aberrant expression of miRNAs leading to GC carcinogenesis. In the last decades, there have been various studies approving the pivotal role of miRNAs in various phases of GC development including cancer initiation, proliferation, migration, invasion, metastasis, angiogenesis, apoptosis, and drug resistance. Therefore, the present review aimed at summarizing the dysregulated miRNAs which contribute to various cellular and developmental mechanisms such as, proliferation, apoptosis, invasion, migration, and angiogenesis. Moreover, it provides an overview on novel miRNAs involved in drug resistance and circular miRNAs as cancer biomarkers. Thereafter, it is hoped that the present study will shed more light on diagnostic and prognostic biomarkers of GC, and potential GC treatments based on miRNAs.

BackgroundPoor sleep may contribute to chronic kidney disease (CKD) through several pathways, including hypoxia-induced systemic and intraglomerular pressure, inflammation, oxidative stress and endothelial dysfunction. However, few studies have investigated the association between multiple objectively measured sleep dimensions and CKD.MethodsWe investigated the cross-sectional association between sleep dimensions and CKD among 1895 Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study participants who completed in-home polysomnography, wrist actigraphy and a sleep questionnaire. Using Poisson regression models with robust variance, we estimated separate prevalence ratios (PR) and 95% CIs for moderate-to-severe CKD (glomerular filtration rate 2 or albuminuria >30 mg/g) among participants according to multiple sleep dimensions, including very short (≤5 hours) sleep, Apnoea−Hypopnoea Index and sleep apnoea-specific hypoxic burden (SASHB) (total area under the respiratory event-related desaturation curve divided by total sleep duration, %min/hour)). Regression models were adjusted for sociodemographic characteristics, health behaviours and clinical characteristics.ResultsOf the 1895 participants, mean age was 68.2±9.1 years, 54% were women, 37% were white, 28% black, 24% Hispanic/Latino and 11% Asian. Several sleep metrics were associated with higher adjusted PR of moderate-to-severe CKD: very short versus recommended sleep duration (PR=1.40, 95% CI 1.06 to 1.83); SASHB (Box-Cox transformed SASHB: PR=1.06, 95% CI 1.02 to 1.12); and for participants in the highest quintile of SASHB plus sleep apnoea: PR=1.28, 95% CI 1.01 to 1.63.ConclusionsSleep apnoea associated hypoxia and very short sleep, likely representing independent biological mechanisms, were associated with a higher moderate-to-severe CKD prevalence, which highlights the potential role for novel interventions.

Aims Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

Key points In most patients with obstructive sleep apnoea (OSA), there is a spontaneous resolution of the breathing disorders during slow wave sleep (SWS) for yet unknown reasons related to non-anatomical factors. Some recently identified forms of neural memory specific of upper airway muscles may play a role in this phenomenon. In the present study, we show for the first time that a form of memory of the genioglossus (tongue) muscle is greatly enhanced during SWS compared to non-rapid eye movement stage 2 sleep. The present study represents a step forward in understanding the mechanisms responsible for the spontaneous development of stable breathing during SWS in OSA patients and may help the discovery of novel therapeutic strategies for this disease. Abstract Several studies have shown that obstructive sleep apnoea (OSA) improves during slow wave sleep (SWS) for reasons that remain unclear. Recent studies have identified forms of neural memory such as short-term potentiation or after-discharge that can occur in response to upper airway obstruction. Neural memory may play a role in the development of stable breathing during SWS by increasing upper airway muscles activity in this sleep stage. We hypothesize that the after-discharge of the genioglossus muscle following upper airway obstruction is enhanced during SWS compared to non-rapid eye movement stage 2 (N2). During sleep, we performed five-breath drops in continuous positive airway pressure (CPAP-drop) to simulate obstructive events and reflexively activate the genioglossus. Immediately afterwards, CPAP was returned to an optimal level. Once the post-drop ventilation returned to eupnoea, the genioglossus after-discharge was measured as the time it took for genioglossus activity to return to baseline levels. In total, 171 CPAP-drops were analysed from a group of 16 healthy subjects and 19 OSA patients. A mixed-model analysis showed that after-discharge duration during SWS was 208% (95% confidence interval = 112% to 387%, P = 0.022) greater than during N2 after adjusting for covariates (ventilatory drive, CPAP levels). There was also a non-significant trend for a -35% reduction in after-discharge duration following an arousal vs. no-arousal from sleep (95% confidence interval = -59.5% to 5%, P = 0.08). Genioglossus after-discharge is two-fold greater in SWS vs. N2, which could partly explain the breathing stabilization described in OSA patients during this sleep stage.

Background MicroRNAs (miRNAs) are effective regulators of gene expression that play a pivotal role in the pathogenesis of colorectal cancer (CRC) and various other cancers. The high prevalence of aberrant miRNA expression in CRC suggests that they can be used as biomarkers and anticancer molecules for therapeutic purposes. There is evidence that microRNA-299-5p (miR-299-5p) is associated with vital cell processes (e.g. epithelial-mesenchymal transition, proliferation, and tumorigenicity) and its improper expression with tumorigenesis in many types of human cancer. This prospective study investigated the contribution of miR-299-5p to CRC tumorigenesis. Methods The real-time reverse transcription-polymerase chain reaction was used to examine miR-299-5p expression levels prospectively in 40 sample pairs of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). The ability of miR-299-5p to function as a tumor marker was also examined. Results The expression levels of miR-299-5p were significantly downregulated in the group of CRC samples compared with matched noncancerous tissue samples. No significant relationship was found between miR-299-5p expression levels and clinicopathological features. Receiver operating characteristic analysis gave an area under the curve of 71% for miR-299-5p with 68% sensitivity and 78% specificity (P=0.001). Conclusion The miRNA miR-299-5p may be considered as a tumor marker in CRC and could be of assistance as a potential predictive biomarker in the diagnosis of this cancer. Keywords Colorectal cancer, biomarker, microRNA, miR-299-5p Ann Gastroenterol 2017; 30 (3): 322-326

MicroRNAs, a class of gene expression regulatory non-coding RNAs, participate in the pathogenic mechanisms of gastric cancer which is one of the life-treating cancers. Due to its aberrant expression in some types of human cancer, miR-383 has the value of being investigated in relation to cancer treatment and diagnosis. MiR-383 is placed in intron of SGCZ, a protein-coding gene, which is subject to dysregulation in various diseases. The purpose of the current study was to investigate the contribution of miR-383 to intestinal-type gastric adenocarcinoma tumorigenesis. The expression level of miR-383 was investigated by qRT-PCR in pairs of tumorous and adjacent tumor-free tissues of 40 patients with gastric cancer during endoscopy. Also, the susceptibility of miR-383 as a tumor marker and the relationship between its aberrant expression and clinicopathological features were determined. qRT-PCR data showed that miR-383 was dysregulated during gastric tumorigenesis. MiR-383 was dramatically downregulated up to sevenfold in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P

Study objectives Arousals from sleep vary in duration and intensity. Accordingly, the physiological consequences of different types of arousals may also vary. Factors that influence arousal intensity are only partly understood. This study aimed to determine if arousal intensity is mediated by the strength of the preceding respiratory stimulus, and investigate other factors mediating arousal intensity and its role on post-arousal ventilatory and pharyngeal muscle responses. Methods Data were acquired in 71 adults (17 controls, 54 obstructive sleep apnea patients) instrumented with polysomnography equipment plus genioglossus and tensor palatini electromyography (EMG), a nasal mask and pneumotachograph, and an epiglottic pressure sensor. Transient reductions in CPAP were delivered during sleep to induce respiratory-related arousals. Arousal intensity was measured using a validated 10-point scale. Results Average arousal intensity was not related to the magnitude of the preceding respiratory stimuli but was positively associated with arousal duration, time to arousal, rate of change in epiglottic pressure and negatively with BMI (R2 > 0.10, P ≤ 0.006). High (> 5) intensity arousals caused greater ventilatory responses than low (≤ 5) intensity arousals (10.9 [6.8-14.5] vs. 7.8 [4.7-12.9] L/min; P = 0.036) and greater increases in tensor palatini EMG (10 [3-17] vs. 6 [2-11]%max; P = 0.031), with less pronounced increases in genioglossus EMG. Conclusions Average arousal intensity is independent of the preceding respiratory stimulus. This is consistent with arousal intensity being a distinct trait. Respiratory and pharyngeal muscle responses increase with arousal intensity. Thus, patients with higher arousal intensities may be more prone to respiratory control instability. These findings are important for sleep apnea pathogenesis.

Introduction Mature microRNAs (miRNAs) are a large class of gene regulators, regulating 60% of mammalian genes. A cluster of miRNAs is located at 14q32.31 chromosomal region; this cluster is associated with human malignancy. MiR-411 is located in chromosomal region 14q32.31 that contains many tumor suppressive microRNAs. This study is designed to investigate the expression of miR-411 in tissue samples of gastric adenocarcinoma compared with their normal compartments, as well as to study the association between miR-411 expression and clinicopathological parameters. Materials The present study included a total of 40 patients (28 males and 18 females) who suffered from gastric cancer between 2014 and 2015. Total RNA was extracted by Trizol solution, and miRNA expression level was examined by qRT-PCR. Results The results revealed that miR-411 was significantly downregulated in the patient group. Moreover, no relation was found between miR-411 expression and clinicopathological figures. Conclusion The results of the present study were consistent with previous reports indicating the downregulation of miR-411 in cancer tissues. The findings of this study may help better understand the molecular mechanism involved in gastric cancer tumorigenesis and confirm that miR-411 can be helpful in distinguishing between malignant and normal gastric cancer tissues.

Study Objectives Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. Methods Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea–hypopnea index [AHI] from baseline plus a treatment AHI Results In addition to age and body mass index (BMI), event depth and expiratory “pinching” (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, “pinched” expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). Conclusions A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.

Study Objectives The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea–hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. Methods Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. Results The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%–10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. Conclusions There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.

Rationale: There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects improve genioglossus muscle activity and upper airway patency during sleep. Objectives: We aimed to determine the effects of the combination of a norepinephrine reuptake inhibitor (atomoxetine) and an antimuscarinic (oxybutynin) on OSA severity (apnea–hypopnea index [AHI]; primary outcome) and genioglossus responsiveness (secondary outcome) in people with OSA. Methods: A total of 20 people completed a randomized, placebo-controlled, double-blind, crossover trial comparing 1 night of 80 mg atomoxetine plus 5 mg oxybutynin (ato–oxy) to placebo administered before sleep. The AHI and genioglossus muscle responsiveness to negative esophageal pressure swings were measured via in-laboratory polysomnography. In a subgroup of nine patients, the AHI was also measured when the drugs were administered separately. Measurements and Main Results: The participants’ median (interquartile range) age was 53 (46–58) years and body mass index was 34.8 (30.0–40.2) kg/m(2). ato–oxy lowered AHI by 63% (34–86%), from 28.5 (10.9–51.6) events/h to 7.5 (2.4–18.6) events/h (P 10 events/hr), AHI was lowered by 74% (62–88%) (P

Aims MicroRNAs (miRs) play pivotal roles in breast cancer development. The dysregulation of miRs has been associated with PD-L1-mediated immune suppression. This study aimed to examine the effect of transfected miR-383-5p on breast cancer cells and T-cells and its association with clinicopathological features in affected patients. Main methods Initially, miR-383-5p and PD-L1 expression levels were investigated in breast cancer tissues. Then, MDA-MB-231 cells were transfected with miR-383-5p mimics to perform analyses. Cell viability was investigated using the MTT assay, and the annexin V/PI staining assay was performed to examine apoptosis induction. Furthermore, the effect of miR-383-5p on cell migration and cell cycle progression was analyzed using the wound-healing assay and flow cytometry, respectively. Gene and protein expressions were studied using qRT-PCR and western blotting. Finally, the effect of miR-383-5p on T-cells, which were co-cultured with cancer cells, was investigated. Key findings Compared to non-malignant tissues, PD-L1 was up-regulated, and miR-383-5p expression was downregulated in breast cancer tissues. Moreover, miR-383-5p reduced breast cancer cell viability via inducing apoptosis and modulating the expression of apoptosis-related genes. Besides, miR-383-5p could inhibit the migration of breast cancer cells via down-regulating metastasis-related genes. Besides, transfected miR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells. Furthermore, the results showed that miR-383-5p might exert its tumor-suppressive effect via inhibiting the PI3K/AKT/mTOR pathway. The inhibitory effect of transfected miR-383-5p on the PI3K/AKT/mTOR pathway might be the underlying mechanism for inhibiting tumoral PD-L1 expression. Significance Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.

We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V′0,passive) and active (V′0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced activePcrit(median (interquartile range) −5.2 (4.3) cmH2O on desipramineversus−1.9 (2.7) cmH2O on placebo; p=0.049) but not passivePcrit(−2.2 (3.4)versus−0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined asV′0,active−V′0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.

MicroRNAs are non-coding RNAs that regulate the gene expression at post-transcriptional level. This futuristic study characterized the contribution of miR-1287 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription–polymerase chain reaction was used to examine miR-1287 expression levels, prospectively in 40 pairs of CRC tissue samples and adjacent noncancerous tissues (>2 cm from cancer tissue). No significant relationship was found between miR-1287 expression levels and clinicopathological features. Showing significant changes overall, MiR-1287 was significantly upregulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver operating characteristic (ROC) curve also showed ROC area (AROC) of 34 % with 1.0 and 0.02 sensitivity and specificity, respectively. Expression of miR-1287, with a value of 0.34, P value = 1.98, and P > 0.05, revealed that this microRNA has a low sensitivity and specificity to be regarded as a tumor marker. With regard to recent increased rate of CRC in the world, the present study may be a contribution, though very small, in the diagnosis and consequently in the treatment of CRC patients.

Introduction The apnea-hypopnea index has been used to characterize obstructive sleep apnea (OSA) severity. However, this metric is limited in providing information about cardiovascular disease (CVD) risk. Recent studies proposed alternative metrics that capture frequency, duration, depth, and combinations of duration and depth of hypoxemia. This study provides a systematic evaluation of the association between conventional or novel nocturnal hypoxemia metrics and the incidence of CVD and CV mortality in the Sleep Heart Health Study (SHHS). Methods We used data from 5,042 participants of the SHHS. Over 10.7 years, there were 1,312 (26.0%) incident CVD events and 359 (7.1%) CV deaths. We calculated standardized (z-scored) values of eight nocturnal hypoxemia indices, including conventional (e.g., oxygen desaturation index) and novel metrics (e.g., hypoxic burden, respiratory event-related area under desaturation curve and desaturation severity, corresponding to alternative quantitative measurements looking at the shape of each desaturation event). The association between each metric and incidence of CVD or CV mortality was evaluated using Cox proportional hazards models. Age, sex, body mass index, race, ethnicity, smoking, total sleep time, number of respiratory events, and prevalent CVD at baseline were used as covariates. Hazard ratios (HR) are presented as the effect of one standard deviation increase in each correponding metric. Results In unadjusted models, all nocturnal hypoxemia indices were associated with increased incidence of CVD and CV mortality. In adjusted models, longer average desaturation duration was associated with lower CVD incidence (HR[95%CI]=0.93[0.86-0.99];p=0.034), higher hypoxic burden with increased CV mortality (HR[95%CI]=1.22[1.04-1.43];p=0.017), and higher % sleep time with oxygen saturation less than 90% (Tlt90%) with increased CV mortality (HR[95%CI]=1.12[1.00-1.26];p=0.040). Conclusion Different metrics of nocturnal hypoxemia derived from polysomnography were associated with CV risk in the SHHS. However, after covariate adjustment, only shorter average desaturation duration, and higher hypoxic burden and Tlt90% were independent CV risk factors. Support AASM Foundation (194-SR-18,188-SR-17); American Heart Association (19CDA34660137); NIH (U01HL53940,U01HL53941,U01HL63463,U01HL53937, U01HL53938,U01HL53916,U01HL53934,U01HL63429,U01HL53931,HL114473, P01HL094307,HL134015,R35HL135818,1R21HL145492-01,R01HL102321,R01HL128658); The State Research Funding (KUH: 5041767, 5041768; TUH: VTR3242, VTR3228, EVO2089), Academy of Finland (313697, 323536), Business Finland (5133/31/2018), Respiratory Foundation of Kuopio Region, Tampere Tuberculosis Foundation, Research Foundation of Pulmonary Diseases, Foundation of Finnish Anti-Tuberculosis Association.

Inspiratory Flow Limitation (IFL) is a phenomenon associated with narrowing of the upper airway, preventing an increase in inspiratory airflow despite an elevation in intrathoracic pressure. It has been shown that quantification of IFL might complement information provided by standard indices such as the apnea-hypopnea index (AHI) in characterizing sleep disordered breathing and identifying subclinical disease. Defining guidelines for visual scoring of IFL has been of increasing interest, and automated methods are desirable to avoid inter-scorer variability and allow analysis of large datasets. In addition, as recording instrumentation and practices may vary across hospitals and laboratories, it is useful to assess the influence of the recording parameters on the accuracy of the automated classification. We employed nasal pressure signals recorded as part of polysomnography (PSG) studies in 7 patients. Two experts independently classified approximately 2000 breaths per subject as IFL or non-IFL, and we used the consensus scoring as the gold standard. For each breath, we derived features indicative of the shape and frequency content of the signals and used them to train and validate a Support Vector Machine (SVM) to distinguish IFL from non-IFL breaths. We also assessed the effect of signal filtering (down-sampling and baseline-removal) on classification performance. The performance of the classifier was excellent (accuracy ~93%) for the raw signals (collected at 125 Hz with no filtering), and decreased for increasing high-pass cut-off frequencies (fc = [0.05, 0.1, 0.15, 0.2] Hz) down to 84% for fc= 0.2 Hz and for decreasing sampling rate (fs = [20, 50, 75, 100] Hz) down to ~85% for fs=20 Hz. Loss of performance was minimized when the classifier was re-trained using data with matched filtering characteristics (accuracy > 89%). We can conclude that the SVM feature-based algorithm provides a reliable and efficient tool for breath-by-breath classification.

Introduction: We hypothesized that individual differences in the pathophysiological traits of obstructive sleep apnea (OSA) influence the efficacy of respiration-synchronized stimulation of the hypoglossal nerve with upper airway stimulation (UAS) therapy. Aims and objectives: We assessed whether patients with greater baseline collapsibility, lower arousal threshold, and/or higher loop gain exhibited the most residual events on UAS therapy. Methods: Polysomnographic (PSG) recordings at baseline and after 12 months of treatment were examined. Pathophysiological traits were estimated from the baseline PSG according to Sands SA et al. AJRCCM 2018. Multivariate regression, adjusting for baseline apnea/hypopnea index (AHI), was used to combine the traits to predict the residual AHI on treatment. Results: Eleven patients including both responders and non-responders have been studied to date. Overall, AHI fell from 37±10/h to 27±12/h (p=0.07, mean±SD) and apnea index (AI) from 14±8/h to 6±5/h (p=0.01). We found no strong univariate predictor of treatment AHI (trends: higher loop gain R=0.32, lower arousal threshold R=-0.29). Multivariate analysis yielded borderline associations with treatment AHI (higher loop gain: β=+7.5±4.5/h, p=0.1; lower arousal threshold: β=-9.6±5.5/h, p=0.1; greater collapsibility: β=+8.0±5.8/h, p=0.2; β±SEM indicates residual AHI per 1 SD increase in trait ("strength"); total trait ΔR2=0.37 after adjusting for baseline AHI). Conclusions: These preliminary results indicate a probable role for greater ventilatory control instability, greater respiratory arousability, and a more collapsible upper airway as causes of incomplete OSA treatment with UAS.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10 -8 ) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

The abnormal expression of microRNAs (miRNAs) plays a key role in colorectal cancer (CRC). The present study attempted to identify the potential miRNA biomarkers of CRC due to the important role of microRNAs within the DLK1-DIO3 genomic region, especially the role of mir-411-5p in other cancers. This prospective study characterized the contribution of mir-411-5p to CRC tumorigenesis. The Real-time quantitative reverse-transcription –polymerase chain reaction was used to examine miR-411-5p expression levels prospectively in 40 pairs of samples of CRC tissues and adjacent noncancerous tissues (>2 cm from cancer tissue). Also, the relationship between miR-411-5p expression levels and clinicopathological characteristics was explored. The capability of miR-411-5p to function as a tumor marker in CRC was also examined. MiR-411-5p was significantly downregulated in a group of CRC samples compared with matched noncancerous tissues. A receiver operating characteristic (ROC) curve also showed ROC area of 68% for miR-411-5p (P value=0.006) with 70% and 65% sensitivity and specificity, respectively. According to the survey results, miR-411-5p might be considered as a tumor marker in CRC and it might be a promising therapeutic option which may help prevent CRC.

Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available.Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography.Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using "gold standard" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11).Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P 0.0001; and R = 0.76, P 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P 0.0001; and R = 0.64, P 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69-86% vs. ventilatory drive measures; P 0.05). Traits were near-identical using nasal pressure versus pneumotach (N = 11, R ≥ 0.98, both traits; P 0.001).Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.

Background: Cancer has significant traumatic effects on the family members of the patients, particularly in Asia's tightly knitted families. Research evidence suggests a debilitating impact of cancer on the quality of life of the afflicted individuals, their spouses, and their families. Since a few studies have been carried out on the quality of life of adolescents living with parents diagnosed with cancer, especially in Iran, the research team decided to evaluate the quality of life of them and also investigate the effects of supportive-educative program on it. Materials and Methods: The present quasi-experimental, one-group study had a pre-test–post-test design and was performed in Esfahan in 2014. The sample of this study consisted of 30 adolescents. The data gathering tool was the short form of quality of life questionnaire (SF-36). Data were analyzed by descriptive statistics and paired sample t-test. P-value of 0.05 was considered significant. Results: The paired sample t-test showed that before and after presenting the program, there were significant statistical differences in some aspects of quality of life, such as physical functioning (P = 0.01), energy/fatigue (P < 0.0001), emotional well-being (P < 0.0001), social functioning (P = 0.001), pain (P < 0.0001), and general health (P = 0.01). Conclusions: This research showed that supportive-educative program can enhance some aspects of quality of life. Therefore, nurses and other health professionals can use this scheme or similar programs for helping adolescents living with a parent with cancer.

Study objectives In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines. Methods Twelve OSA patients (apnea-hypopnea index >15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure). Results Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 ± 20 vs. 213 ± 18 mL/min), despite elevated respiratory effort during stable breathing (26 ± 2 versus 23 ± 2 cmH2O, p = .03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p = .04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO2 by 14% in both cases (p = .02, .03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort. Conclusions OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events.