Sleep and Breathing

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Comparison of mRNA expression levels of ferroptosis-related molecules between IH group and NC group. IH significantly decreased the expression levels of GPX4, xCT, FTH1, and FACL4 (a and b). IH intermittent hypoxia. p < 0.05, **p < 0.01, and ***p < 0.001
Effect of IH treatment on myocardial damage. a and b Western blotting assays for Bax, Bcl-2, and caspase-3 protein levels have shown that IH contributes to apoptosis and Fer-1 and N-acetylcysteine treatment could alleviate the damage of myocardial tissue. Protein levels were normalized to GAPDH. FIH ferrostatin-1 + IH, AIH N-acetylcysteine + IH, IH intermittent hypoxia; n = 3. Data are presented as the mean ± SD of three independent experiments. p < 0.05, **p < 0.01, and ***p < 0.001
Effect of IH treatment on ferroptosis in myocardial tissues. a and b Western blotting assays for GPX4, xCT, FTH1, and FACL4 protein levels. IH could induce ferroptosis in myocardial tissues and Fer-1 and N-acetylcysteine treatment could relieve it (a and b). Protein levels were normalized to GAPDH. FIH ferrostatin-1 + IH, AIH N-acetylcysteine + IH, IH intermittent hypoxia; n = 3. Data are presented as the mean ± SD of three independent experiments. p < 0.05, **p < 0.01, and ***p < 0.001
Effect of IH treatment on ERS in myocardial tissues. a–d Western blotting assays for NOX4, P53, CHOP, and PERK protein levels. IH could active ERS in myocardial tissues and Fer-1 and N-acetylcysteine treatment could relieve it (a and d). Protein levels were normalized to GAPDH. ERS endoplasmic reticulum stress, IH intermittent hypoxia, FIH ferrostatin-1 + IH, AIH N-acetylcysteine + IH; n = 3. Data are presented as the mean ± SD of three independent experiments. p < 0.05, **p < 0.01, and ***p < 0.001
Article
  • Jiefeng HuangJiefeng Huang
  • Hansheng XieHansheng Xie
  • Yisong YangYisong Yang
  • [...]
  • Qi-Chang LinQi-Chang Lin
Purpose Obstructive sleep apnea (OSA) is related to increased risk of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS). Methods AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis. Results The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of ferroptosis and ERS. Inhibition of ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS. Conclusions Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.
 
Experimental design proposed to carry out this study. OSA, obstructive sleep apnea; BMI, body mass index; FICF, free and informed consent form; PSG, polysomnography; CPAP, continuous positive airway pressure; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale; SSS, Stanford Sleepiness Scale; KSS, Karolinska Sleepiness Scale; MFIS, Modified Fatigue Impact Scale; FOSQ, Functional Outcomes of Sleep Questionnaire; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; PVT, psychomotor vigilance task; MWT, maintenance of wakefulness test; MAD, mandibular advancement device
Flow chart of study participants
Article
Objective This study’s objective was to compare the best long-term treatment, mandibular advancement device (MAD) or continuous positive airway pressure (CPAP), for patients with mild obstructive sleep apnea (OSA) in improving excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life. Methods This study was a single-blind, parallel, randomized clinical trial with controls. The sample was composed of individuals between 18 and 65 years of age with a body mass index of < 35 kg/m² and apnea/hypopnea index above five and less than 15. Participants were submitted to physical examination, polysomnography, and the following questionnaires: Pittsburgh Sleep Quality Index, Berlin Questionnaire, Epworth Sleepiness Scale, Stanford Sleepiness Scale, Karolinska Sleepiness Scale, Modified Fatigue Impact Scale, Functional Outcomes of Sleep Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. They were also presented with the following tests: maintenance of wakefulness test and psychomotor vigilance task. Results Of 79 patients, 25 were in the MAD group, 31 in the CPAP group, and 23 in the control group. Polysomnographic parameters were best normalized with CPAP compared with MAD. Fatigue was improved in the MAD and CPAP groups, with no difference between these treatments. Quality of life was also improved with both treatments, but CPAP was superior to MAD. Daytime sleepiness, mood, and sustained attention showed no difference with the interventions. Greater adherence was obtained with MAD patients than with CPAP measured by hours of use. Conclusions Treatment with CPAP was better at normalizing polysomnographic parameters and improving quality of life in patients with mild OSA. Both treatments improved fatigue with no difference between the two treatments. Neither treatment improved daytime sleepiness, mood or sustained attention. Clinical Trials Database NTC01461486.
 
Article
Purpose Patients with obstructive sleep apnoea (OSA) have a high incidence of vascular endothelial injury. The most important pathophysiological feature of OSA is chronic intermittent hypoxia (CIH). This study aimed to investigate the mechanisms of CIH-related vascular endothelial injury. Methods IH exposure was applied to human umbilical vein endothelial cells (HUVECs). After modeling, cell viability, the expression levels of peroxisome proliferator activated receptor γ (PPARγ), apoptosis-associated proteins and mitochondrial division fusion proteins, and the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed via Cell Counting Kit-8 (CCK-8), western blotting, fluorescent microscope, and flow cytometry, respectively. Rosiglitazone (PPARγ agonist), tempo (the mitochondrial-specific antioxidant), and tempo combined with PPARγ interfering RNA were used to treat HUVECs, respectively. Results After IH exposure, cell viability and levels of MMP decreased, cell apoptosis and ROS levels increased, and the expression levels of PPARγ decreased. Both tempo and rosiglitazone pretreatment ameliorated cell apoptosis and improved cell viability. In addition, mitochondrial function became better after tempo pretreatment. PPARγ interference reversed the protective effects of tempo on IH-related mitochondrial function injury and cell injury. Conclusions PPARγ regulated the apoptosis and cell viability of IH-treated HUVECs by altering mitochondrial function. This finding clarifies the mechanism of CIH-related vascular endothelial injury.
 
Article
Introduction: Floppy eyelid syndrome (FES) is an underdiagnosed condition stereotypically found in obese, middle-aged men, characterized by a lax eyelid tarsus which readily everts without excess mechanical manipulation. Obstructive sleep apnoea (OSA) is the most frequently reported comorbidity in patients suffering from FES. The aim of this study was to determine whether or not individuals with FES present with distinct anthropometric characteristics in comparison to patients without FES suspected of having OSA. Methods: A retrospective case-control study in which FES patients and controls all referred for investigation of suspected OSA, matched for sex, ethnicity, residential location, age (± 2 years), date of sleep study (± 1 month), and type of sleep study were compared for anthropometric, comorbidity, and sleep data differences. Results: OSA prevalence and severity, assessed by apnoea-hypopnea index (AHI), revealed no significant differences between patients with FES (n = 39) and those without (n = 75), (85% vs 88%, p = 0.91 and 31.9 ± 28.7 vs 28.5 ± 16.6, p = 0.81 respectively), despite patients with FES being more obese (p = 0.02). Patients with FES had significantly lower Epworth sleepiness scale (ESS) scores after treatment with CPAP (5.3 ± 4.1 vs 9.4 ± 5.0, p = 0.028). Patients with FES exhibited increased prevalence of hernias (15% vs 4%, p = 0.032), dermatological (41% vs 17%, p = 0.006) and rheumatological (15% vs 3%, p = 0.012) comorbidities. Conclusion: FES patients appear to exhibit a distinct phenotype with increased prevalence of comorbidities related to matrix metalloproteinase dysfunction and significant improvement of daytime hypersomnolence with continuous positive airway pressure (CPAP) treatment.
 
The VOTE classification
PSG at baseline versus PSG at 3 months follow-up with MAD in situ
Predictors known to influence MAD treatment outcome
Potential predictors for dropout
Article
Purpose Previous studies have shown a wide range of efficacy (29 to 71%) of a mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA). Currently, the ability to preselect suitable patients for MAD therapy based on individual characteristics related to upper airway collapsibility is limited. We investigated if the use of non-custom interim MAD during drug-induced sleep endoscopy (DISE) could be a valuable screening tool to predict MAD treatment outcome. Methods In a single-center prospective study including a consecutive series of patients with OSA, we compared DISE outcomes with a MAD in situ with polysomnography results after 3 months of using the same MAD that was used during DISE. Results Of 41 patients who completed the study, the median apnea–hypopnea index (AHI) was 16.0 events/h [IQR 7.4–23.4]. Respiratory outcomes on polysomnography, including apnea index (AI), total AHI, AHI in supine position, and oxygen desaturation index, all significantly improved after 3 months of MAD treatment. With complete improvement of the upper airway obstruction with the MAD in situ during DISE in supine position, patients were 6.3 times more likely to be a responder to MAD treatment compared to patients with a persisting complete obstruction, although not statistically significant (OR 6.3; 95%CI 0.9–42.7; p = 0.060). Conclusion The potential predictive value with regard to MAD therapy outcomes of the use of an interim MAD during DISE would be an important finding, since the prediction of MAD therapy outcome is of great clinical and scientific interest. A study with a larger cohort should be performed to further investigate our findings.
 
The workflow for screening publications according to inclusion and exclusion criteria
Article
Purpose Obstructive sleep apnea (OSA) can impair cognition. Continuous positive airway pressure (CPAP) is a recommended treatment for OSA but its effectiveness on cognitive improvement is uncertain, a finding which may be biased by various durations and adherence to treatment with CPAP. In a meta-analysis assessing high-quality randomized controlled trials (RCTs), we estimated whether or not CPAP benefits cognition in patients with OSA. Methods PRISMA criteria were followed in the performance of this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) of six neuropsychological scores covering eight cognitive domains were used to evaluate the benefit between CPAP and non-CPAP interventions. Subgroups of different therapeutic durations and adherence, which were divided into short-term (< 8 weeks) and long-term (≥ 12 weeks) durations, and poor (nighttime < 4 h/night) and good (nighttime ≥ 4 h/night) adherence were also analyzed. Results Among 16 RCTs, 1529 participants with OSA were included. Comparing the CPAP group and the control group for all treatment durations and adherence, a mild improvement for digit span forward which reflected short-term memory was observed (WMD[95%CI] = 0.67[0.03,1.31], p = 0.04). Trail making test-part B, which reflected executive function was improved for participants with OSA who had good adherence to CPAP (WMD[95%CI] = − 6.24[− 12.60,0.12], p = 0.05). Patients with OSA who received short-term CPAP treatment (WMD[95%CI] = − 7.20[− 12.57, − 1.82], p = 0.009) had a significant improvement in executive function when compared with controls. There was no statistical difference for all scales between long-term (≥ 12 weeks) CPAP treatment group and control group. Conclusion The effectiveness of CPAP on cognitive improvement in patients with OSA is limited, although good adherence to CPAP can mildly benefit executive function with short-term effectiveness.
 
Numbers of screened, excluded, and enrolled patients. Legend: IPF: idiopathic pulmonary fibrosis
Data from cardiopulmonary exercise testing in IPF patients without and with sleep-related breathing disorders. “x” denotes the respective mean values. Legend: SRBD: sleep-related breathing disorders; V′CO2: carbon dioxide output; V′E: minute ventilation; %pred: percent of predicted value
Representative PSG data from a subject with detected central apnea events
Article
Purpose Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear. Patients and methods In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied. Results A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74 years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V′O2(AT) 618.5 ml/min vs. 774.0 ml/min (p = 0.043)) and exhibited a significantly higher V′E/V′CO2(peak) of 43.0 l/l vs. 38.5 l/l (p = 0.037). In search of predictors for SRBD by logistic regression, workload(peak)%pred was identified as a significant variable (p = 0.033). Conclusions SRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.
 
Article
Background Adolescents with sedentary behavior, spending many hours in front of the television and electronic devices, develop early involvement of cardiovascular disease and obesity. These sedentary behaviors increased significantly in this age group during the pandemic of 2020/2021. Sleep directly influences aspects of health, such as blood pressure and cardiac autonomic balance and exercise has a protective effect on these same physiological parameters. Objective This study aimed to examine whether or not physically active adolescents positively influence HRV and cardiovascular parameters despite poor sleep quality. Methods This is an analytic and transversal study. Sleep quality, physical activity levels, blood pressure, and heart rate variability (HRV) were measured. Two-way ANOVA and Tuckey post hoc test evaluated the difference between groups. Results Among 352 adolescents entrolled, mean age was 15.8 ± 0.24 years. It was observed that compared to the physically active group with poor sleep quality, the sedentary poor sleep quality group presented a more significant deficit in blood pressure and autonomic parameters such as pNN50, SD1, and HF. Conclusion Adolescents who practiced physical activity regularly have shown better HRV and sleep quality compared with sedentary adolescents.
 
Diagram detailing participant recruitment and flow through the study procedures. OSAsNO, OSA without (sans) nasal obstruction group; OSAwNO, OSA with nasal obstruction group; NOSE questionnaire, The Nasal Obstruction Symptom Evaluation (NOSE) questionnaire; AHI, apnea–hypopnea index
Total nasal resistance (inspiration) (Pa/cm³/s) with postural change in the three groups. Comparison across groups at each postural: the total nasal resistance (total NR) difference was only significant in the supine postural, showing OSA without nasal obstruction group had lower supine total NR (marked with * in B). Comparison among postural in each group: compared with sitting postural, total NR was higher in supine and lateral postural in Control group (marked with † in A) and was higher in lateral postural in both OSA group (marked with † in B, C). Compared with supine postural, total NR was higher in right lateral postural in Control group (marked with ‡ in A) and was higher in left and right lateral postural in OSA without nasal obstruction group (marked with ‡ in B), but had no different in OSA with nasal obstruction group. There was no difference in total NR between left and right postural in each group. *p < 0.05 compared with the control group; †p < 0.05 compared with sitting posture; ‡p < 0.05 compared with supine posture
Nasal resistance increment during sitting to supine postural change. *p < 0.05 compared with control; **p < 0.01 compared with control; ins, inspiration; exp, expiration
Article
Objective Increased nasal resistance (NR) can augment upper airway collapse in patients with obstructive sleep apnea (OSA). Posture change can lead to altered nasal resistance. Our study aimed to investigate the influence of posture changes on NR in patients with OSA. Methods Healthy controls without subjective nasal obstruction (apnea–hypopnea index (AHI) < 5 events/h), patients with OSA and subjective nasal obstruction, and patients with OSA and no subjective nasal obstruction were recruited. NR was measured by active anterior rhinomanometry in sitting, supine, left-lateral, and right-lateral postural positions. Total NR and postural change-related NR increments were calculated and compared among groups. Results In total, 26 healthy controls and 72 patients with OSA (mean AHI 39.7 ± 24.8 events/h) were recruited. Of patients with OSA, 38/72 (53%) had subjective nasal obstruction. Compared with controls, patients with OSA and no subjective nasal obstruction had lower total NR (inspiration, p = 0.037; expiration, p = 0.020) in the supine postural position. There was no difference in sitting, left-lateral, and right-lateral total NR among groups. Total NR was higher in lateral compared to sitting posture in both patients with OSA and in controls. The NR increment for sitting to supine postural change was significantly lower in patients with OSA (inspiration, p = 0.003; expiration, p = 0.005) compared with controls. The change in NR showed no statistically significant difference among groups in supine-left or supine-right postural change. Conclusion Patients with OSA had lower supine total NR and lower total NR increment in the sitting to supine postural change, which may be related to a different posture-related NR regulatory mechanism. This study provides a new exploratory direction for the compensatory mechanism of the upper airway to collapse during sleep.
 
AHI distribution
BMI distribution
Correlation between AHI and BMI in group 1
Correlation between AHI and BMI in group 2
Low AT and severity of OSA
Article
Introduction Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma. Methods A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%. Results Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference ( p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant. Conclusions This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor.
 
Article
Objective To investigate the association between multimorbidity and sleep medication use in women. Methods A population-based cross-sectional study was conducted on women (20–69 years) in Southern Brazil. Sleep medications were identified using the Therapeutic and Chemical Anatomical Classification. Multimorbidity was operationalized according to two cutoff points: diagnosis of either two or more or three or more chronic conditions and presence or absence of obesity. Explanatory variables included sociodemographic, behavioral, and health factors including obesity and common mental disorders (CMD) (assessed using the Self-Reporting Questionnaire 20 for CMD). Crude and adjusted prevalence ratios (PR) and 95% confidence intervals (95%CIs) were estimated with Poisson regression with robust variance using various adjustment models. Results In a sample of 1128 women, the prevalence of sleep medications was 14.3% (95%CI 12.2–16.3). After adjustments, the association between multimorbidity and sleep medication use yielded the following PR: multimorbidity ≥ 2:1.78 (95%CI, 1.23–2.56) and multimorbidity ≥ 3:1.90 (95%CI, 1.36–2.68). When obesity was included in the model, the effect was in the same direction but smaller, indicating that the presence of multimorbidity had an independent effect on the use of sleep medications, even after adjusting for CMD. Conclusion The presence of multimorbidity increased the probability of using sleep medications by approximately 80%, regardless of the observed cutoff point, inclusion of obesity in multimorbidity, and adjustment for CMD. Specific aspects of some chronic conditions may interfere with sleep quality, predisposing women to begin use of these medications at early ages and, consequently, to continue their use throughout later life.
 
Flow diagram of literature search
Forest plot for the change in serum testosterone concentration between OAS group and control group in men
Forest plot for subgroup analysis of the change in serum testosterone concentration between the men and women
Sensitivity analyses
The funnel plot
Article
Purpose Testosterone deficiency (TD) negatively affects male sexuality, reproduction, general health, and quality of life. In recent years, decreased serum testosterone levels have been reported to be caused by obstructive sleep apnea (OSA). However, these results are controversial and lack the support of a large number of high-quality studies. Hence, we performed a meta-analysis to assess the association between OSA and serum testosterone levels. Methods To identify eligible studies, we conducted a systematic retrieval in the electronic databases (PubMed, Web of Science, the Cochrane Library, EMBASE) from their inception to September 2021. We chose studies with definitive diagnoses of OSA, including effects of OSA on testosterone level. Random effect model was used for analysis. Results This meta-analysis included 24 case–control studies with 1389 patients (1268 male patients) and 845 controls (745 male control). The serum testosterone levels in the male OSA group were significantly lower than that of control group [SMD = − 0.97, 95% CI (− 1.47, − 0.47)], while there was no difference in female patients with OSA and control [SMD = 0.06, 95% CI (− 0.22, 0.33)]. Subgroup analysis showed that race, age, body mass index (BMI), and detection method were the reason for high heterogeneity (I² = 94.9%). Conclusions The results indicated that OSA is significantly correlated with the decrease in serum testosterone levels in men. Male patients with OSA should be alerted to secondary diseases caused by low testosterone levels.
 
Article
Purpose Circadian rhythm affects maximal short-term performance, and it is an important determinant of the training component. This review aimed to summarise the influence of circadian rhythm on peak and mean power output of muscle, fatigue index, and blood lactate levels. Methods English language articles were searched through the following databases: PubMed, Web of Science, Science Direct, and Google Scholar, and pertinent randomized control trials were scrutinized. Results The search revealed 17,481 articles, and 29 were included in this systematic review based on inclusion and exclusion criteria. Randomized control trials were selected, and the methodological validity of articles was evaluated using the ‘Cochrane risk of bias tool’. Findings suggest that outcome variables muscle peak power output (p < 0.0001, Z = 7.22, I² = 57.42, SMD = − 0.91, 95% confidence interval CI = − 1.16, − 0.67), muscle mean power output (p < 0.0001, Z = 5.66, I² = 83.85, SMD = − 0.75, 95% CI = − 1.01, − 0.49), and fatigue index (p = 0.02, Z = 2.41, I² = 2.49, SMD = − 0.39, 95% CI = − 0.72, − 0.07) were higher in the evening while the level of blood lactate was higher in the morning (p = 0.79, Z = 0.27, I² = 0.73, SMD = − 0.05, 95% CI = − 0.46, − 0.35). Conclusion The results show that diurnal variation affects both peak and mean power output of muscle as well as fatigue index. However, there is no remarkable effect of circadian rhythm on blood lactate level. A major factor attributed to this finding was the variation in the training experience of participants. For an effective training prescription, it is very important to consider the effect of the biological clock on muscle power output since anaerobic exercise performance is discernibly influenced by the time of the day.
 
Graphical representation of the scoring undertaken, and intervention provided for each group at each time-point (n = 10 scorers from 5 sleep centres for each group). Scoring reliability was measured at baseline, 3 months and 6 months (grey horizontal bars) using the same 16 PSG fragments at each time point and for each group. EPT PSGs were used to provide EPT reports to the EPTPassive and EPTActive groups. Training PSGs were used to provide EPT reports and active method alignment training to the EPTActive group only. EPT external proficiency testing, PSG polysomnography
Event-by-event reliability for respiratory event scoring (a) and arousal scoring (b) measured using PSA, as well as epoch-by-epoch reliability of sleep scoring (c) measured using К, for Control, EPTPassive, and EPTActive groups, at baseline and after 6 months of intervention. Control group: received no feedback on performance; EPTPassive group: received EPT reports only; EPTActive group: received EPT and method alignment intervention. EPT external proficiency testing, PSA proportion of specific agreement, К Cohen’s kappa statistic. White circles represent the median from 15 PSGs for each scorer; black squares represent back-transformed group means. *p < 0.05 compared to baseline
Article
Purpose This study evaluated whether or not polysomnography (PSG) inter-scorer reliability (ISR) across sleep centres could be improved by external proficiency testing (EPT), or by EPT combined with method alignment training. Methods Experienced scorers form 15 sleep centres were randomised to the following: (1) a control group, (2) a group that received a self-directed intervention of EPT reports (EPTPassive) or (3) a group that received an active intervention of method alignment training and EPT reports (EPTActive). Respiratory, arousal and sleep scoring ISR from sixteen PSG fragments were compared between groups across time. Results Among 30 scorers, there were no ISR changes in controls between baseline (BL) and 6 months (6 m). Both EPT groups showed ISR improvement from BL to 6 m for respiratory, arousal and sleep scoring (p < 0.05). Respiratory scoring back-transformed mean (95CI) proportion of specific agreement (PSA) for the EPTPassive group improved from 0.78 (0.72–0.84) to 0.80 (0.74–0.86) and for the EPTActive group from 0.80 (0.74–0.85) to 0.82 (0.76–0.88). Arousal scoring PSA for the EPTPassive group improved from 0.72 (0.66–0.77) to 0.74 (0.69–0.79) and for the EPTActive group from 0.71 (0.65–0.76) to 0.77 (0.72–0.82). Sleep scoring kappa for the EPTPassive group improved from 0.64 (0.58–0.69) to 0.73 (0.68–0.77) and for the EPTActive group from = 0.75 (0.71–0.80) to 0.80 (0.76–0.85). Overall, poorer performers achieved greater improvement. Conclusion External proficiency testing produced modest, statistically significant PSG inter-scorer reliability improvements among experienced scorers across sleep centres, with potential to improve clinical management of individual patients and increase research study statistical power.
 
PRISMA flow diagram
Article
Purpose Obstructive sleep apnoea (OSA) is a common, significantly underdiagnosed sleep-related breathing disorder, characterised by upper airway collapse and resultant intermittent hypoxia. Oxygen plays an important role in collagen synthesis and as a result in wound healing. An association between OSA and wound healing has not been clearly delineated. A systematic review was performed to understand this association. Methods Randomised controlled trials, cohort, cross-sectional and case–control studies evaluating the relationship between OSA or OSA-related symptoms and wound healing in adult populations were searched in the systematic review using electronic databases PubMed, EMBASE and Ovid MEDLINE. Main results A total of 11 cohort studies and 1 case–control study with a total of 58,198,463 subjects were included. Most studies suggest that patients diagnosed with OSA or who are at high risk of having OSA are more likely to suffer from wound complications. Patients with OSA have been found to be at higher risk for post-operative wound infection and wound dehiscence. Contradictory results were obtained on time to heal, with one study concluding that individuals with OSA were more likely to heal earlier when compared to patients without OSA. Quality of evidence, however, was deemed very low due to high risk of bias. Conclusions This systematic review did identify an association between OSA and wound healing. However, due to the very low-quality evidence, further research is warranted to better characterise this association and investigate whether or not treating OSA can indeed affect wound healing.
 
Operating room setting
Tasks performed: (1a-b) zooming in and focusing onto two specific structures; (2) positioning Tabotamp® gauze over a rectangle on the soft palate
Response to each questionnaire item, divided according to age (< 40 vs > 40 years)
Comparison of visualization of the surgical field in the setting of direct-vision surgery (A) and exoscope-assisted surgery (B)
Article
Purpose The application of 3D exoscopic technology is spreading worldwide, in several surgical scenarios. In this study, we present the first-time use of the exoscopic system (VITOM® and Versacrane™) in a cadaver simulation of transoral Snore Surgery. Methods All participants (n = 14) were asked to perform 2 exercises that simulate tasks required in Snore Surgery, they were then administered a questionnaire assessing their evaluation of the applied exoscopic technology. Participants were divided into groups according to age and experience. Results Mean zooming and focusing time was higher in young surgeons than in seniors, and similar results were obtained for mean procedural times. The responses to the questionnaire showed that in the vast majority (86%), the exoscopic technology was well rated. Conclusion The exoscope can be considered a useful tool, thanks to its magnifying power and high-definition images, as well as for its indirect ability to enhance staff involvement in the procedure and for educational purposes.
 
The process of creating a score; OSA, Obstructive sleep apnea; PSG, polysomnography; KCMH, King Chulalongkorn Memorial Hospital
The diagnostic performance of NH-OSA in each cohort
Performance of the NH-OSA score for each possible threshold, an online calculator
Article
Background: Diagnosis of obstructive sleep apnea requires polysomnography which has limited availability. We aimed to develop and validate a risk score in predicting clinically significant OSA among the Thai population. Methods: We reviewed polysomnographic studies performed in adults diagnosed with OSA in King Chulalongkorn Memorial Hospital from 2017 to 2019. 1798 and 450 patients were randomly enrolled in development and validation cohorts, respectively. A risk score was developed using multiple factor analysis and logistic regression. The NH-OSA score was externally validated at the Bangkok Christian Hospital. We compared its performance to existing screening scores (STOP-BANG, Berlin Questionnaire, Epworth Sleepiness Scale (ESS), and NoSAS score). Result: The NH-OSA score allocates 1 point for having neck circumference ≥ 13 inches (in women) or 15 inches (in men), 4 points for the presence of hypertension, 3 or 5 or 7 points for having a body mass index of 23-24.9, 25-30, ≥ 30 kg/m2, respectively, 9 points for the presence of moderate or severe snoring, and 5 points for age ≥ 40 years. With a cutoff value at 14 points, the sensitivity and specificity were 82.1% and 68.7%, respectively. The AUC was 0.75 (0.73-0.78). Both internal and external validation study revealed high AUC of 0.74 (0.68-0.80) and 0.75 (0.60-0.90), respectively. These were greater when compared to STOP-BANG, Berlin Questionnaire, ESS, and NoSAS score. Conclusion: NH-OSA is a newly developed tool which has good performance in predicting clinically significant OSA with high validity among the Thai population. It could help screen patients at risk of OSA for further investigation.
 
This image depicts the measurement of lateral pharyngeal wall thickness. The white arrowheads represent the internal wall of internal carotid artery and the white arrows represent the pharynx. The distance between the two points represents the lateral pharyngeal wall thickness on that side
The image depicts the measurement of tongue base thickness. The white bold arrow represents the skin surface and the thin arrows highlight the tongue surface. The red arrow represents the tongue base. The distance between these two points is taken as tongue base thickness
Scatter plot demonstrating relationship between AHI and TBT
Scatter plot demonstrating relationship between AHI and LPWT
Receiver operating characteristics (ROC) curve for predicting the probability of severe OSA using neck circumference, TBT, and LPWT
Article
Introduction In resource-limited settings, obstructive sleep apnea (OSA) often goes undiagnosed as polysomnography (PSG) is expensive, time-consuming, and not readily available. Imaging studies of upper airway have been tried as alternatives to PSG to screen for OSA. However, racial differences in upper airway anatomy preclude generalizability of such studies. We sought to test the hypothesis that ultrasonography (USG), an inexpensive, readily available tool to study soft tissue structures of the upper airway, would have predictive value for OSA in South Asian people. Methods Adult patients with sleep-related complaints suspicious for OSA were taken for overnight PSG. After the PSG, consecutive patients with and without OSA were studied with submental ultrasonography to measure tongue base thickness (TBT) and lateral pharyngeal wall thickness (LPWT). Results Among 50 patients with OSA and 25 controls, mean age was 43.9 ± 11.4 years, and 39 were men. Patients with OSA had higher TBT (6.77 ± 0.63 cm vs 6.34 ± 0.54 cm, P value = 0.004) and higher LPWT (2.47 ± 0.60 cm vs 2.12 ± 0.26 cm, P value = 0.006) compared to patients without OSA. On multivariate analysis, TBT, LPWT, and neck circumference were identified as independent factors associated with OSA. These variables could identify patients with severe OSA with a sensitivity of 72% and a specificity of 76%. Conclusion Patients with OSA have higher tongue base thickness and lateral pharyngeal wall thickness proportionate to the severity of the disease, independent of BMI and neck circumference. These findings suggest that sub-mental ultrasonography may be useful to identify patients with severe OSA in resource-limited settings.
 
Article
Purpose Chronic intermittent hypoxia (CIH) is a major cause of cognitive dysfunction in people with obstructive sleep apnea syndrome (OSAS), as it damages synapse structure, and function. This study aimed to investigate the potential mechanisms resulting in cognitive impairment caused by CIH in patients with OSAS. Methods Healthy adult SD male rats (n = 36) were randomly divided into four groups: control, CIH, WP1066, and dimethyl sulfoxide (DMSO). The CIH, WP1066, and DMSO groups were exposed to intermittent hypoxic environments for 8 h per day for 28 d. The WP1066 group received intraperitoneal injection of WP1066, a selective signal transducer and activator of transcription-3 (STAT3) inhibitor. All the experimental rats were subjected to the Morris water maze. Hippocampal tissue samples (n = 6 per group) were used for western blot analysis, and brain tissue samples (n = 3 per group) were used for immunohistochemistry and hematoxylin and eosin staining. Results The cognition of rats exposed to prolonged CIH was impaired. P-STAT3 expression was found to be higher in CIH rats than in control rats. Postsynaptic density95 (PSD95) expression was significantly reduced in rats with CIH-induced learning and memory impairment, but it significantly increased after the STAT3 signaling pathway was blocked, which improved learning and memory ability. However, inhibition of the STAT3 signaling pathway failed to improve the decline of synaptophysin (SYP) protein caused by CIH. Conclusions When rats are exposed to CIH, STAT3 in the brain is activated, PSD95 and SYP levels decrease, and cognition is impaired. Inhibition of the STAT3 signaling pathway increases PSD95 to recover postsynaptic plasticity, thereby improving cognitive dysfunction.
 
Study flow chart
Proportion of time in supine position according to sleep study type and OSA diagnosis
Article
Purpose Different devices have been used for the diagnosis of obstructive sleep apnea (OSA), which differ in the number of sensors used. The numerous sensors used in more complex sleep studies such as in-lab polysomnography may influence body position during sleep. We hypothesized that patients submitted to in-lab polysomnography (PSG) would spend more time in the supine position than patients submitted to an ambulatory Portable Monitor (PM) sleep study. Methods Body position during PSG and PM studies was compared among two distinct groups of patients matched for age, body-mass index (BMI), apnea–hypopnea index (AHI), and gender. Predictors of time spent in the supine position were determined using a multiple linear regression model. Results Of 478 participants who underwent either PSG or PM studies, mean age: 61[43–66] years; males: 43.9%; BMI: 28.4[26.1–31.1]kg/m²; AHI 14[7–27] events/hour). Participants who underwent PSG studies spent more time in the supine position (41[16–68]% than participants who underwent PM studies (34[16–51]%), P = 0.014. Participants with OSA spent more time in the supine position than participants without OSA, both among the PSG and PM groups P < 0.05). Gender, BMI, OSA severity, and sleep study type were independent predictors of time spent in the supine position. Conclusion In-lab PSG may increase time spent in the supine position and overestimate OSA severity compared to a PM sleep study. OSA diagnosis is also associated with increased time spent in the supine position. The potential influence on the sleeping position should be taken into account when choosing among the different sleep study types for OSA diagnosis.
 
Distribution of various parameters in each cluster. Footnotes: Blue shade represents presence of the variable; white shade represents absence of the variable. For continuous variables (WHR, neck circumference) the distribution of the variable in each cluster around the population mean is depicted.
Predictive importance of various parameters in defining clusters
Article
Purpose Over the last decade, advances in understanding the pathophysiology, clinical presentation, systemic consequences and treatment responses in obstructive sleep apnea (OSA) have made individualised OSA management plausible. As the first step in this direction, this study was undertaken to identify OSA phenotypes. Methods Patients diagnosed with OSA on level 1 polysomnography (PSG) were included. Clinical and co-morbidity profile, anthropometry and sleepiness scores were compiled. On PSG, apnea–hypopnea index, positional indices, sleep stages and desaturation indices (T90) were tabulated. Cluster analysis was performed to identify distinct phenotypes among included patients with OSA. Results One hundred patients (66 males) with a mean age of 49.5 ± 13.3 years were included. Snoring was reported by 94% subjects, and 50% were excessively sleepy. Two-thirds of subjects had co-morbidities, the most frequent being hypertension (55%) and dyslipidemia (53%). Severe OSA was diagnosed on PSG in 42%, while 29% each had mild and moderate OSA, respectively. On cluster analysis, 3 distinct clusters emerged. Cluster 1 consisted of older, obese subjects with no gender predilection, higher neck circumference, severe OSA with more co-morbidities and higher T90. Cluster 2 comprised of younger, less obese males with snoring, witnessed apnea, moderate and supine predominant OSA. Cluster 3 consisted of middle-aged, obese males with lesser co-morbidities, mild OSA and lower T90. Conclusions This study revealed three OSA clusters with distinct demographic, anthropometric and PSG features. Further research with bigger sample size and additional parameters may pave the way for characterising distinct phenotypes and individualising OSA management.
 
Mandibular advancement splint
Study flowchart
Individual AHI results (n = 15)
Article
Purpose: Sleep-disordered breathing (SDB) is common in pregnancy and is associated with adverse health consequences for both mother and child. Mandibular advancement splints (MAS) have been shown to improve sleep quality, daytime sleepiness and snoring in non-pregnant women. The effectiveness of MAS for treating SDB in pregnancy is unknown. This pilot study aimed to evaluate the efficacy and adherence to MAS in pregnant women with SDB. Methods: Women with mild-moderate SDB (apnea-hypopnea index (AHI) 10-29/h) on level 2 polysomnography (PSG) performed at 22.0 ± 5.5 weeks' gestation were treated with a MAS during pregnancy to 6 months postpartum. An embedded micro-recorder measured adherence. PSG was repeated while on titrated treatment, and off treatment in the postpartum period. Results: Among 17 women completing the study, MAS was worn ≥ 4 h/night for 57.5 ± 36.7% of nights during the antepartum period. While using MAS, nightly snoring time decreased from 25.9 ± 24.5% at baseline to 6.4 ± 7.8% when treated during pregnancy (p = .003). AHI decreased from 17.6 ± 5.1 to 12.9 ± 6.3 (p = .02) and fell by ≥ 30% and below 15/h in 60% of participants. During the postpartum period, MAS was used for ≥ 4 h/night on 24.8 ± 27.9% of nights. Moreover, the mean AHI off MAS was 17.9 ± 13.1; 88% of women had persistent SDB (AHI ≥ 10). Conclusions: In this cohort, treatment efficacy and objective adherence were variable. Device use was less frequent in the postpartum period even though a substantial number of women had persistent SDB after delivery. Clinical trial registered with www. Clinicaltrials: gov number: NCT03138291.
 
Consort flow diagram of the study. PTSD, post-traumatic stress disorder; CPAP, continuous positive airway pressure; RBD, REM-related behavioral disorder; RLS, restless leg syndrome; RES, residual excessive sleepiness
Percentage of veterans with residual excessive sleepiness (RES) as a function of CPAP use
Article
Purpose The causes of residual excessive sleepiness (RES) in patients with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are multifactorial and modulated by comorbid conditions. The aim of the present study was to elucidate clinical and polysomnographic determinants of RES in continuous positive airway pressure (CPAP)-adherent OSA veterans with PTSD. Methods The study protocol consisted of a retrospective analysis of consecutive cases of patients with PTSD who presented to the Veterans Affairs sleep clinics with adequately treated OSA between June 1, 2017 and October 15, 2021. Based on the Epworth Sleepiness Scale (ESS), patients were categorized into RES (ESS ≥ 11) and no RES (ESS < 11) groups. Demographic and PSG data were subjected to univariate and multivariate analyses to ascertain predictive factors of RES. Results Out of 171 veterans with PTSD who were adherent to CPAP, 59 (35%) continued to experience RES. The RES group had a decrease in mean ESS score of 1.2 ± 4.5 after CPAP treatment compared with 4.6 ± 4.9 for the no RES group (< 0.001). A dose–response was observed between CPAP use and RES (p = 0.003). Multivariate regression analysis identified higher baseline ESS (OR 1.30; 95% CI 1.16–1.44), greater percentage of time spent in REM sleep (OR 0.91; 95% CI 0.85–0.96), CPAP use less than 6 h (OR 2.82; 95% CI 1.13–7.01), and a positive screen for depression (OR 1.69; 95% CI 1.03–4.72) as independent predictors of RES in patients with PTSD and OSA. Conclusion RES is highly prevalent in patients with PTSD and OSA despite adherence to CPAP and is independently associated with percentage time spent in REM, duration of CPAP utilization, and symptoms of depression.
 
Pie chart showing prevalence data for reported “eye problems” in 259 sleep clinic patients. Cataracts (10%); corneal abrasion (1%); diabetic retinopathy (1%); dry eyes (1%); Fuch’s syndrome (1%); glaucoma (1%); herpetic lesion (1%); macular degeneration (1%); pterygium (surfer’s eye, 2%); no eye problem (76%); unspecified (3%); other (9%). Note: (1) does not include reports of long/short sightedness or use of spectacle/contact lenses; (2) total > 100% because some individuals reported more than one “eye problem”
Pie chart showing prevalence data for retinal abnormalities identified by retinal photography in 396 sleep clinic patients. No pathology (7%); non-specific maculopathy (3%); peripapillary atrophy (PPA, 47%); retinopathy (8%); large cup (5%); naevus (11%); epiretinal membrane (10%; consisting of epiretinal membrane only (1%), surface wrinkling (3%) and cellophane reflex (8%); early age-related macular degeneration (AMD, 9%); intermediate AMD (11%); late AMD (1%); pale disc (1%); retinal emboli (0.3%); macular telangiectasis (0.3%); viterous detachment (4%); macular hole (1%); other pathologies (7%); drusen number < 10 (56%); drusen number ≥ 10 (15%)
Example of peripapillary atrophy observed in a sleep clinic patient. Retinal photograph showing peripapillary atrophy (PPA; white arrow) in a 53-year-old male with very severe OSA (AHI: 81.3 events/h)
Article
Study objectives There has been long-standing interest in potential links between obstructive sleep apnea (OSA) and eye disease. This study used retinal photography to identify undiagnosed retinal abnormalities in a cohort of sleep clinic patients referred for polysomnography (PSG) and then determined associations with PSG-quantified sleep-disordered breathing (SDB) severity. Methods Retinal photographs ( n = 396 patients) were taken of each eye prior to polysomnography and graded according to validated, standardized, grading scales. SDB was quantified via in-laboratory polysomnography (PSG; n = 385) using standard metrics. A questionnaire ( n = 259) documented patient-identified pre-existing eye disease. Within-group prevalence rates were calculated on a per patient basis. Data were analyzed using multivariate logistic regression models to determine independent predictors for retinal abnormalities. P < 0.05 was considered significant. Results Main findings were (1) 76% of patients reported no pre-existing “eye problems”; (2) however, 93% of patients had at least one undiagnosed retinal photograph-identified abnormality; (3) most common abnormalities were drusen (72%) and peripapillary atrophy (PPA; 47%); (4) age was the most common risk factor; (5) diabetes history was an expected risk factor for retinopathy; (6) patients with very severe levels of SDB (apnea hypopnea index ≥ 50 events/h) were nearly three times more likely to have PPA. Conclusion Retinal photography in sleep clinic settings will likely detect a range of undiagnosed retinal abnormalities, most related to patient demographics and comorbidities and, except for PPA, not associated with SDB. PPA may be indicative of glaucoma, and any association with severe SDB should be confirmed in larger prospective studies.
 
Frequency of responses to the attitude items concerning the importance of OSA and its diagnosis, Brazil, 2021
Frequency of responses to attitude items (C-D-E) concerning one’s confidence in the identification and treatment of OSA, Brazil, 2021. (*OSA, obstructive sleep apnea; CPAP, continuous positive airway pressure)
Article
Purpose To analyse the psychometric properties of the translated and cross-culturally adapted version of the OSAKA (Obstructive Sleep Apnea Knowledge and Attitudes) questionnaire in the Brazilian Portuguese language. Methods The OSAKA instrument was translated by two independent translators, and the back-translated conciliated version was presented and approved by Washington University, which holds the intellectual property for the OSAKA questionnaire. Physicians from different specialties electronically completed the OSAKA instrument and the ASKME (Assessment of Sleep Knowledge in Medical Education) questionnaire, which was used as an auxiliary instrument to analyse the construct validity. Results The questionnaire was tested with 176 physicians. The items from the knowledge and attitudes domains presented acceptable internal consistency values, with McDonald’s omega coefficients (Ω) of 0.70 and 0.73, respectively. The OSAKA questionnaire showed a moderate correlation with the ASKME instrument (r = 0.60, p < 0.001) and excellent retest reliability, with an intraclass correlation coefficient of 0.81. There were differences in knowledge between the medical specialties (p < 0.001). Regarding attitudes, most respondents considered obstructive sleep apnoea and its diagnosis to be important and felt confident in identifying it, but the same majority did not feel confident in treating the disease. Conclusion The OSAKA instrument, as a translated and cross-culturally adapted Brazilian Portuguese version, presented psychometric properties with adequate reliability and validity.
 
Expansion appliances. A Tooth tissue-borne. B Tooth-bone. C Bone-borne
Application of the polygraphy on the patient
CONSORT flow diagram
Article
Background The purpose of this clinical study was to assess the effects of different rapid maxillary expansion appliances on the severity of obstructive sleep apnea (OSA). Material and methods Patients having a narrow maxilla and identified with OSA were divided randomly into three groups: tooth tissue-borne, tooth-borne, and bone-borne expanders. Changes in sleep parameters at baseline and 3-month follow-up detected by polygraphy were the primary outcome. Treatment of the crossbite was the secondary outcome. Dunn-Bonferroni tests, Kruskal–Wallis, and Wilcoxon analysis were applied for intra- and inter-group differences at p < 0.05 significance level. Results Among 46 patients randomized, apnea-hypopnea index (AHI) changed from baseline to follow-up in all groups (− 1.6, p = 0.280; 0.6, p = 0.691; − 0.45, p = 0.796, respectively), with no between-group difference (p = 0.631). Oxygen desaturation index (ODI) altered from baseline to follow-up in all groups (0.80, p = 0.977; 0.20, p = 0.932; and − 1.00, p = 0.379, respectively), with no between-group difference (p = 0.858). There was no significant difference in minimum oxygen saturation from baseline to follow-up in all groups (0.00, p = 0.401; − 2.00, p = 0.887; 0.50, p = 0.407, respectively). No significant changes were observed in supine AHI from baseline to follow-up in all groups (0.00, p = 0.581; − 1.00, p = 0.393; 0.00, p = 0.972, respectively). The upper intermolar width increased from baseline to follow-up in all groups (5.04, p = 0.000; 3.15, p = 0.001; 5.41, p = 0.00, respectively) with no between-group difference (p = 0.560). Maxillary width increased from baseline to follow-up in all groups (4.25, p = 0.001; 4.74, p = 0.00; 4.49, p = 0.001, respectively) with no inter-group difference (p = 0.963). Conclusions The amount of skeletal and dental expansion obtained in the maxilla was similar in all groups. Rapid maxillary expansion was not found to be effective in OSA treatment. Trial registration ClinicalTrials.gov Identifier: NCT04604392.
 
Flowchart of propensity score matching, which was used to assemble well-balanced groups based on the variables age, BMI and baseline AHI. ESS, Epworth Sleepiness Scale; HNS, hypoglossal nerve stimulation; PAP, positive airway pressure; ESS, Epworth Sleepiness Scale; BMI, body mass index; AHI, apnea–hypopnea index
Comparison of mean absolute reduction of ESS in participants with UAS and PAP from baseline to 12-month follow-up (p = 0.042). ESS, Epworth Sleepiness Scale; HNS, hypoglossal nerve stimulation; PAP, positive airway pressure
Mean disease alleviation (MDA) for PAP and HNS therapy. MDA is equal to the surface area of the rectangle for which the length is given by the adjusted adherence (usage time/total sleep time), and the height is given by the therapeutic efficacy (AHI baseline minus AHI with therapy applied, expressed in percentage). MDA provides a measure of overall therapeutic effectiveness. PAP, positive airway pressure; HNS, hypoglossal nerve stimulation
Article
Purpose Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea–hypopnea index (AHI), and (3) effectiveness. Methods Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated. Results Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP. Conclusion Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments. Trial registration ClinicalTrial.gov Identifier: NCT03756805.
 
Recruitment procedure
Article
Purpose This study aimed to assess the prevalence of poor sleep quality and to describe its predictors in diabetic patients having chronic venous insufficiency and varicose veins treated with cyanoacrylate glue. Methods This single-center, prospective cohort study was conducted between March 2018 and March 2021. A total of 103 patients with diabetes mellitus and chronic venous insufficiency (CEAP classification at stages C3–C6) treated with cyanoacrylate glue for varicose veins were recruited. A questionnaire form, Pittsburg Sleep Quality Index, Berlin Questionnaire, and Diagnostic Criteria for Restless Legs Syndrome were used for data collection. A Doppler USG assessment was performed in the first clinical examination. Results Almost half of the participants had had diabetes mellitus for 10 years or more, and 52% had good glucose control. Among the study sample, 61% were poor sleepers, 47% of the participants were RLS positive, and 51% had a high risk of sleep apnea. RLS, HbA1c, and dressing at home had positive associations with poor sleep quality (p < 0.05) on the fifth day after the peripheral embolization. One month after the operation, participants had better sleep quality; however, there were no statistically significant differences between the assessments of RLS and the risk of OSA compared to the fifth day after the operation (p > 0.05). Conclusions This prospective study showed that restless legs syndrome, a high level of HbA1c, and dressed injection area of the skin are associated with poor sleep quality in patients with diabetes having chronic venous insufficiency and varicose veins treated with cyanoacrylate glue. Additionally, participants had better sleep quality 1 month after the peripheral embolization compared to the fifth day after the operation.
 
PRISMA flow chart of the review
Article
Background Adolescence is a developmental period characterised by rapid physical and psychological changes that heighten the risk for inadequate sleep. Fortunately, physical activity programs (PAPs) are an easy-to-do intervention that has been associated with improved sleep outcomes in different population groups. This systematic review aimed to provide evidence to support the effects of PAPs on sleep outcomes among apparently healthy adolescents. Methods A systematic literature search was performed in online databases of PubMed, Cochrane Library, and PEDro for all dates up to April 2022. All relevant clinical trials reporting on the effects of PAPs on sleep among adolescents were included using a pre-defined inclusion/exclusion criterion (PROSPERO: CRD42020171852). The methodological quality of the included studies was assessed using ‘specific checklists per design’ (RCTs) provided by the Dutch Cochrane Centre. Qualitative synthesis was used to report the results of the review. Results Two RCTs were included and analysed in the review. Both studies were of good methodological quality but lacked blinding. The PAPs in the reviewed studies included mainly aerobic exercises in the form of cross-country running in the mornings, SMS-delivered motivational messages to increase daily step counts, and use of a pedometer and step diaries. Sleep was measured both subjectively by means of sleep questionnaires and objectively using sleep electroencephalographic recordings. Nevertheless, qualitative synthesis is suggestive of an overall positive effect of PAPs on some sleep outcomes in adolescents, albeit with limited to moderate evidence. Conclusion PAPs appear to have a beneficial effect on some sleep outcomes among apparently healthy adolescents. Nevertheless, the body of evidence is currently scanty, thus warranting the need for more high-quality RCTs.
 
Article
Purpose Habitual snoring (HS) is a prominent symptom of sleep-disordered breathing; thus, it is also important to consider the associated, multidimensional risk factors for HS in children. This study was aimed to identify risk factors for HS in children. Methods A cross-sectional survey was performed in Chengdu. Children aged 2–14 years from four districts were randomly chosen to participate. Questionnaires were voluntarily completed by the children’s guardians. Results The survey included 926 boys and 622 girls, who were an average of 6.4 ± 3.0 years old. The sample included 463 habitual snorers (30.4%), 683 occasional snorers (44.8%), and 402 nonsnorers (26.4%). HS was found in 51.8% of children under 7 years old and 26.6% of children aged 7 years old or older. The prevalence of pregnancy complications was significantly lower in mothers who bore children with HS (p = .006). Among the HS group, 86.6% had an immediate family member who snores. Breastfeeding duration among the HS group was significantly less than among the occasional snoring and nonsnoring groups. History of symptoms of allergic rhinitis, rhinosinusitis, tonsillitis, and pneumonia/bronchitis in the past 6 months was associated with HS. Likewise, maternal smoking during pregnancy, maternal exposure to secondhand smoke during pregnancy, and child exposure to secondhand smoke were also associated with HS. Conclusion The prevalence of HS was higher in children under 7 years old. Having a mother with more education, a family history of snoring, a shorter period of breastfeeding, upper respiratory tract inflammation, and passive smoking are important risk factors for HS. Pregnancy complications may be associated with lower prevalence of snoring in childhood.
 
Flow diagram of literature selection according to PRISMA
Forest plots for the influence of OSA on the prevalence of periodontitis
Forest plots for the influence of OSA on PD and CAL: A PD, B CAL
Forest plots for the influence of OSA on BOP, PI and GI: A BOP, B PI, C GI
Forest plots for the influence of OSA on BOP, in the studies employed polysomnography for the diagnostic of OSA
Article
Purpose The present meta-analysis aimed to evaluate quantitively the recent scientific evidence regarding the association between obstructive sleep apnea (OSA) and periodontitis. Methods Databases searched were PubMed, EMBASE, Scopus, and Web of Science. Publications were included according to the inclusion criteria. The following outcomes were evaluated: the prevalence of periodontitis, probing depth (PD), clinical attachment loss (CAL), the percentage of sites with bleeding on probing (BOP), plaque index (PI), and gingival index (GI). The statistical analysis was processed using the software STATA. Results Thirteen eligible studies comprising a total of 31,800 patients were included. The meta-analysis showed an increased prevalence of periodontitis in OSA populations compared to controls. Both PD and CAL were increased in OSA populations compared with controls. (Prevalence of periodontitis: OR 2.348; 95%CI 2.221–2.482; PD: SMD = 0.681, 95% CI: 0.062–1.301, Z = 2.61, P = 0.031; CAL: SMD = 0.694, 95% CI: 0.167–1.22, Z = 2.58, P = 0.01). The study also found significantly increased BOP in patients with OSA after heterogeneity was clarified. (SMD = 0.357, 95% CI: 0.079–0.635, Z = 2.52, P = 0.012). Conclusions The findings suggest that OSA was associated with an increased prevalence of periodontitis.
 
Article
Purpose Body composition is considered to be associated with obstructive sleep apnea (OSA) severity. This cross-sectional study aimed to examine associations of overnight body composition changes with positional OSA. Methods The body composition of patients diagnosed with non-positional and positional OSA was measured before and after overnight polysomnography. Odds ratios (ORs) of outcome variables between the case (positional OSA) and reference (non-positional OSA) groups were examined for associations with sleep-related parameters and with changes in body composition by a logistic regression analysis. Results Among 1584 patients with OSA, we used 1056 patients with non-positional OSA as the reference group. We found that a 1-unit increase in overnight changes of total fat percentage and total fat mass were associated with 1.076-fold increased OR (95% confidence interval (CI): 1.014, 1.142) and 1.096-fold increased OR (95% CI: 1.010, 1.189) of positional OSA, respectively (all p < 0.05). Additionally, a 1-unit increase in overnight changes of lower limb fat percentage and upper limb fat mass were associated with 1.043-fold increased OR (95% CI: 1.004, 1.084) and 2.638-fold increased OR (95% CI: 1.313, 5.302) of positional OSA, respectively (all p < 0.05). We observed that a 1-unit increase in overnight changes of trunk fat percentage and trunk fat mass were associated with 1.056-fold increased OR (95% CI: 1.008, 1.106) and 1.150-fold increased OR (95% CI: 1.016, 1.301) of positional OSA, respectively (all p < 0.05). Conclusion Our findings indicated that nocturnal changes in the body’s composition, especially total fat mass, total fat percentage, lower limb fat percentage, upper limb fat mass, trunk fat percentage, and trunk fat mass, may be associated with increased odds ratio of positional OSA compared with non-positional OSA.
 
Flowchart showing exclusion criteria and group assignment for all pregnant women records available in our REDCap database. Continuous positive airway pressure (CPAP) compliance criteria were > 4 h average use, 70% of the time or greater, for the remainder of pregnancy following OSA diagnosis and CPAP initiation
Article
Purpose To evaluate whether or not continuous positive airway pressure (CPAP) treatment in pregnancies complicated by obstructive sleep apnea (OSA) is associated with a decrease in hypertensive disorders of pregnancy. Methods This was a retrospective cohort study of perinatal outcomes in women who underwent objective OSA testing and treatment as part of routine clinical care during pregnancy. Where diagnostic criteria for OSA were reached (respiratory event index (REI) ≥ 5 events per hour), patients were offered CPAP therapy. Obstetrical outcomes were compared between the control group (no OSA), the group with untreated OSA (OSA diagnosed, not CPAP compliant), and the group with treated OSA (OSA diagnosed and CPAP compliant), with CPAP compliance defined as CPAP use ≥ 4 h, 70% of the time or greater. A composite hypertension outcome combined diagnoses of gestational hypertension (gHTN) and preeclampsia (PreE) of any severity. Results The study comprised outcomes from 177 completed pregnancies. Our cohort was characterized by obesity, with average body mass indices > 35 kg/m², and average maternal age > 30 years old. CPAP was initiated at an average gestational age of 23 weeks (12.1–35.3 weeks), and average CPAP use was 5.9 h (4–8.5 h). The composite hypertension outcome occurred in 43% of those without OSA (N = 77), 64% of those with untreated OSA (N = 77), and 57% of those with treated OSA, compliant with CPAP (N = 23) (p = 0.034). Conclusion Real-world data in this small study suggest that CPAP therapy may modulate the increased risk of hypertensive complications in pregnancies complicated by OSA.
 
ROC curve of multivariate logistic regression model. The good level of accuracy for the model was confirmed by an AUC = 0.91 (P < 0.0001)
Scatterplot showing linear relationship of log-transformed TST90 and AHI. The regression line slope shows the higher dependency of TST90 from AHI in male patients
Linear relationship of log-transformed TST90 and daytime PaO2. The greater slope of the regression line in male population reveals how TST90 changes are more influenced by PaO2 variations
Scatterplot showing a substantial lack of dependency of TST90 from AHI in patients with a previous diagnosis of COPD
Linear relationship of log-transformed TST90 and daytime PaO2. Patients suffering from COPD had a TST90 being not significantly influenced by daytime PaO2
Article
Purpose The impact of obstructive sleep apnea syndrome (OSAS) in terms of mortality, morbidity, and quality of life has been well established. Phenotyping OSAS is essential in order to make the best therapeutic choice. A particular subset of patients with OSAS shows nocturnal respiratory failure, defined by a nighttime oxygen saturation <90% in more than 30% of the total sleep time (TST90). The aim of this study was to identify possible predictive factors for nighttime respiratory failure (NRF) in patients with OSAS. Methods In this retrospective study, patients with suspected OSAS who underwent a sleep study were enrolled. Of 116 patients with moderate/severe OSAS who met the inclusion criteria, 67 also had nocturnal respiratory failure. We compared clinical, anthropometric, and laboratory data in patients with OSAS vs. OSAS and nocturnal respiratory failure. Results Patients with OSAS and nocturnal respiratory failure were more frequently female, had a higher BMI, lower daytime oxygen partial pressure (PaO2) in arterial blood, higher Apnea Hypopnea Index (AHI), and a lower number of sleep hours per night. Chronic obstructive pulmonary disease (COPD) was more diagnosed in the group of patients with nocturnal respiratory failure. A lower number of total sleep hours, lower daytime PaO2, lower AHI, increased oxygen desaturation index (ODI), and the presence of a diagnosed COPD were all found to increase the risk of having nocturnal respiratory failure. Conclusion COPD, AHI, ODI, daytime PaO2, and total sleep hours are the main predictors for NRF in patients with moderate and severe OSAS.
 
SDB in MR patients. Data are presented as n; %. MR, mitral regurgitation; SDB, sleep-disordered breathing
SDB subtypes in MR patients with SDB. Data are presented as n; %. MR, mitral regurgitation; CSA, central sleep apnoea; MSA, mixed sleep apnoea; OSA, obstructive sleep apnoea; SDB, sleep-disordered breathing
Change in AHI after TVMR in patients with and without central sleep apnoea. AHI, apnoea-hypopnoea index (AHI); TMVR, transcatheter mitral valve repair
Left-atrial volume index (LAVI) in patients with mitral regurgitation and central sleep apnoea before and after transcatheter mitral valve repair. n = 8
Article
Purpose The relationship between chronic heart failure and sleep-disordered breathing (SDB) has been frequently described. However, little is known about the association of mitral regurgitation (MR) and SDB or the impact of transcatheter mitral valve repair (TMVR) on SDB. Our aims were first to determine the prevalence of SDB in patients with MR, and second to determine the effect of TMVR on SDB. Methods Patients with MR being evaluated for TMVR at the University Hospital Bonn underwent polygraphy (PG) to determine the prevalence of SDB. After TMVR, a subset of patients was followed up with transthoracic echocardiography (TTE) and PG to evaluate the effect of TMVR on SDB. Results In 53 patients, mean age was 76.0 ± 8.5 years and 62% were male. Patients predominantly had more than moderate mitral regurgitation (94%). SDB was highly prevalent (68%) with predominantly central sleep apnoea (CSA, 67%). After TMVR in 15 patients, the apnoea/hypopnoea index (AHI) and central apnoea index (AI) were significantly reduced among patients with SDB (AHI − 8.0/h, p = 0.021; central AI − 6.9/h, p = 0.046). The left atrial volume index (LAVI) at baseline was significantly higher in patients with CSA than in patients with obstructive sleep apnoea (OSA) and was significantly reduced after TMVR (63.5 ml/m² ± 27.2 vs. 38.3 ml/m² ± 13.0; − 18.4 ml/m², p = 0.027). Conclusion SDB, especially CSA, is highly prevalent in patients with mitral regurgitation. In the follow-up cohort TMVR led to a significant reduction of the AHI, predominantly of central events. The findings of the study suggest that TMVR may be a suitable therapy not only for MR but also for the accompanying CSA. LAVI may be a useful indicator for CSA in patients with MR.
 
Article
Purpose: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO2. Whether this approach may be relevant to other populations, especially slowly progressive neuromuscular diseases (NMD), is unknown. Methods: This study was conducted as a post hoc analysis from a previously published randomized controlled trial (NCT03458507). Patients with NMD treated with domiciliary NIV were stratified according to the level of ventilatory support: high-level tidal volume (HLVT; mL/kg of predicted body weight [PBW]) or high-level pressure support (HLPS), defined as a value above median value of the whole population (> 6.8 mL/kgPBW or 9.0 cmH2O, respectively). Primary outcome was mean nocturnal transcutaneous CO2 pressure (PtcCO2). Secondary outcomes included adherence to NIV, leaks, and side effects. Results: Of a total of 26 patients, 13 were exposed to HLVT, with significantly lower nocturnal PtcCO2 (respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg, p = 0.002). A linear correlation between VT (mL/kgPBW) and mean nocturnal PtcCO2 was evidenced (r = - 0.59, 95%CI [- 0.80; - 0.25], p = 0.002). No significant impact of HLVT was found on secondary outcomes. Conclusion: Despite the lack of power of this post hoc analysis, our results suggest that higher levels of ventilatory support are correlated with lower PtcCO2 in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO2 evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders.
 
Flow chart showing recruitment of patients. *Excluded as device unable to record compliance. Auto-CPAP, auto continuous positive airway pressure
Article
Rationale Despite increased recognition of sleep disordered breathing in hospitalized patients, studies are lacking on the impact of inpatient adherence with positive airway pressure (PAP) therapy on post-discharge adherence. Objectives To assess the predictive value of inpatient adherence to PAP therapy on post-discharge compliance and adherence. Methods We reviewed data on individuals as part of a registry of a hospital-based sleep medicine program between August 2019 and December 2020. Consecutive patients identified as high risk for sleep disordered breathing based on our 2-tier screening process and initiated on Auto-PAP (APAP) therapy were included. Their adherence and post-discharge course were recorded. Primary objectives were polysomnography (PSG) compliance, sleep medicine clinic follow-up compliance, and 30-day adherence to PAP therapy if indicated by PSG. Results In total, 900 individuals were screened during the study period. Of these, 281 were offered inpatient PAP therapy. Patients on bilevel PAP therapy (88 patients) were excluded due to lack of objective compliance recording. Final analysis was performed on 193 patients. Of the 193 patients placed on inpatient APAP, 140 (73%) were adherent to the therapy with average usage of 367 min per day versus 140 min per day in the non-adherent (p < 0.001). There was no significant difference in oxygen desaturation index between the adherent and non-adherent groups (32.4 ± 21.9 events per hour and 34.5 ± 21.9 events per hour consistent; p = 0.5). No demographic and anthropometric characteristics or comorbid conditions were noted. Those who were adherent to PAP therapy in-hospital 47/140 (34%) underwent ambulatory PSG post-discharge compared to 7/53 (13%) of those non-adherent in-hospital (p = 0.002). The adherent group also had significantly higher likelihood for post-discharge clinic follow-up (p = 0.01) and adherence to outpatient PAP therapy (p = 0.01). Conclusions Hospitalized patients identified as high risk for sleep disordered breathing have high adherence to PAP therapy during hospitalization and inpatient adherence predicts outpatient follow-up (both PSG testing and sleep clinic) and home PAP adherence.
 
Article
Background This international study aimed at determining current routine palate surgeries and surgical methods adopted by otolaryngologists who practice surgical management of obstructive sleep apnea (OSA). Methods An international online survey was developed with the collaboration of the YO-IFOS (Young Otolaryngologists-International Federation of Otorhinolaryngological Societies) to assess the current routines in palatal procedures. The surgeons were asked 33 multiple-choice questions. Results A total of 141 sleep surgeons answered the questionnaire, of whom 27% were from Africa, 30% from Asia, 24% from Centre-South America, and 19% from Europe. According to otolaryngology surgical specialties, 51% were sleep surgeons, 31% general ENTs, 8% Rhinologists, 7% Head & Neck surgeons, 2% otologists, and 1% maxillofacial surgeons. Of the 141 respondents, 51% answered they were sleep specialists, whereas 49% were non-sleep specialists. According to specific medical degree, 38% were specialists, 33% were consultants, 25% were professors, and 4% were residents or trainees. Conclusion This study gives an overview of the current surgical practice in OSA management in otolaryngology in different countries.
 
Flow chart of article selection
Forest plot for the association between shift work and TSH
Forest plot for the association between shift work and FT4
Forest plot for the association between shift work and the risk of positive thyroid autoantibodies
Article
Purpose Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. Methods Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle–Ottawa scale was used to assess the quality of included studies. The Mantel–Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I² statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. Results Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05–0.55; P = 0.02; I² = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02–0.40; P = 0.03; I² = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62–2.55; P = 0.52; I² = 63%). Conclusion Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.
 
Model-based simulation of sleep–wake cycles with earlier and later weekday risetimes. A–C Simulations of the sleep–wake cycles in samples with weekday risetime (RT) earlier than 7:00 a.m. and at 7:00 a.m. or later (RT < 7 and RT ≥ 7, n = 443 and 367, respectively) on the interval of 10 days (A) and two subintervals (B, C). Two alternating phases of the sleep–wake regulating process (i.e., wake and sleep states) are simulated as exponential buildups and decays of S(t) with additional modulation of the parameters of these exponential buildups and decays (1) by sine-form function with 24-h period (2). The risetimes and bedtimes on free days serve as the initial times for the buildup and decay phases of the 24-h sleep–wake cycle. They resemble empirical data averaged for weekends in Fig. 3, but additionally suggest the full compensation of the earlier weekday wakeups by the advance shift of the circadian phase and sleep timing in earlier risers. The whole list of parameters of the model is given in supplementary Table A1 of Appendix B. Sd(t) and Sb(t) refer to the highest expected buildup and lowest expected decay of S(t) predicted by these simulations (1)–(2). As shown in the simulations (A), at any of 10 days, a switch from buildup phase to decay phase occurs exactly at Sd(t). In other words, throughout the whole interval of 10 cycles (Sa-Su, Mo-Fr, Sa-Su, and Mo), S(t) does not build up above Sd(t), including the subinterval of 5 weekdays between Mo and Fr (i.e., when, near the end of the weekday decay phase, S(t) does not reach Sb(t) due to early morning wakeups). S(t) for SD: the hypothetical case of sleep deprivation from the first night the first Mo (B). Only such SD caused by prolongation of wakefulness on night hours can lead to a further buildup of S(t) above Sd(t). This hypothetical further buildup might be associated with the accumulation of “sleep debt” that must be “paid back” during the following recovery night. Evidence for such a further buildup was not provided by the simulations of sleep times in samples with RT < 7 and RT ≥ 7 (Table 2 and Fig. 3). Throughout 5 weekdays, S(t) does not build up above Sd(t), even when weekday RT < 7 due to earlier wakeups. The simulations suggested that weekend sleep duration is identical in these subsets, even in the cases when weekday sleep duration is shorter after earlier weekday RT than after later weekday RT. At any of the simulated days, there exists the difference between two subsets of samples in the circadian phase (C). Symbols additionally illustrate bedtimes and risetimes (BT&RT) predicted for free days and empirical data on weekday and weekend rise-and bedtimes (BT and RT) for these two subsets of samples (Fig. 3)
Model-based simulation and bedtimes and risetimes in students with early and later school start times. A–C Simulations of the interval of 10 days (A) and two subintervals of this interval, weekday night between Wednesday and Thursday (B), and weekend night between Saturday and Sunday (C). Symbols additionally illustrate empirical data on bedtimes and risetimes from Table 1 (right) for students with early and later school start times (mean values for 35 pairs of samples). Despite a shorter weekday sleep duration in students with early school start time (B), these simulations suggested the identical duration of weekend sleep after early and later school start times (A, C). Since the advance shift of weekday wakeups differed after early and later school start times (i.e., it was larger after early school start time), this difference leads to the difference in the timing of light exposure that, in turn, leads to the difference in the circadian phase. The difference in the advance shift also explains the difference in weekday sleep duration (i.e., weekday sleep was shorter after early school start time)
Sleep times in 443 and 367 samples with earlier and later weekday risetimes. A–D 12 sleep times. Age: sleep times in samples with earlier and later weekday risetime (RT either < 7 or ≥ 7) were calculated separately for 7 age groups (0–11, 11–14, 14–16, 16–19, 19–25, 25–45, and 45–85 years, n = 140, 124, 128, 109, 115, 120, and 74, respectively). Additionally, the lines paralleled X-axis illustrate mean sleep times for earlier and later RT obtained by averaging over 7 age groups in two-way ANOVAs. Clock hour or hour ± SEM: mean sleep time for the subsets of samples with earlier and later weekday RT and standard error of this mean. See Table 2 (right) for the results of statistical comparison of two subsets of the whole set of samples with earlier and later weekday RT, and Table 1 (left) for the results of comparison of samples from one of age groups (> 14 and ≤ 16 years)
Article
Background Many people believe they sleep for longer time on weekend nights to make up for sleep lost on weekdays. However, results of simulations of risetimes and bedtimes on weekdays and weekends with a sleep–wake regulating model revealed their inability to prolong weekend sleep. In particular, they predicted identical durations of weekend sleep after weeks with relatively earlier and relatively later risetime on weekdays. In the present study, this paradoxical prediction was empirically confirmed. Methods Times in bed were calculated from weekday and weekend risetimes and bedtimes in pairs of samples of students with early and later school start time and in subsets of samples from 7 age groups with weekday risetime earlier and later than 7:00 a.m. Results Among 35 pairs of students, mean age ± standard deviation was 14.5 ± 2.9 years and among the age group samples, 21.6 ± 14.6 years. As predicted by the simulations, times in bed on weekends were practically identical in the samples with early and later school start time and in two subsets with earlier and later weekday risetime. Conclusions The model-based simulations of sleep times can inform an individual about an amount of irrecoverable loss of sleep caused by an advance shift of wakeups on weekdays.
 
Article
Purpose: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). Methods: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. Results: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. Conclusion: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.
 
Article
Purpose Obstructive sleep apnea syndrome (OSAS) is an important, modifiable risk factor in the pathophysiology of arrhythmias including atrial fibrillation (AF). The purpose of the study was to evaluate cardiac electrophysiologists’ (EPs) perception of OSAS. Methods We designed a 27-item online Likert scale–based survey instrument entailing several domains: (1) relevance of OSAS in EP practice, (2) OSAS screening and diagnosis, (3) perception on treatments for OSAS, (4) opinion on the OSAS care model. The survey was distributed to 89 academic EP programs in the USA and Canada. While the survey instrument questions refer to the term sleep apnea (SA), our discussion of the diagnosis, management, and research on the sleep disorder is more accurately described with the term OSAS. Results A total of 105 cardiac electrophysiologists from 49 institutions responded over a 9-month period. The majority of respondents agreed that sleep apnea (SA) is a major concern in their practice (94%). However, 42% reported insufficient education on SA during training. Many (58%) agreed that they would be comfortable managing SA themselves with proper training and education and 66% agreed cardiac electrophysiologists should become more involved in management. Half of EPs (53%) were not satisfied with the sleep specialist referral process. Additionally, a majority (86%) agreed that trained advanced practice providers should be able to assess and manage SA. Time constraints, lack of knowledge, and the referral process are identified as major barriers to EPs becoming more involved in SA care. Conclusions We found that OSAS is widely recognized as a major concern for EP. However, incorporation of OSAS care in training and routine practice lags. Barriers to increased involvement include time constraints and education. This study can serve as an impetus for innovation in the cardiology OSAS care model.
 
Flow chart showing the inclusion of patients in the present study
Proportion of patients without obstructive sleep apnea–hypopnea syndrome (OSAHS) and mild, moderate, and severe OSAHS in the present study. More than half the patients were diagnosed with moderate or severe OSAHS
Article
Purpose To investigate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) and analyze the effects of OSAHS on the incidence of post-OPCABG complications, length of stay in intensive care unit (ICU) and hospitalization, and hospital expense. Materials and methods This prospective study included patients undergoing OPCABG at Beijing An Zhen hospital from January 2018 to December 2018. OSAHS was diagnosed by using a portable sleep monitor before surgery. Results Among 74 patients, the prevalence of OSAHS and moderate to severe OSAHS (apnea hypopnea index (AHI) ≥ 15) was 70% and 53%, respectively. Compared with the no to mild OSAHS group (AHI < 15), the moderate to severe OSAHS group presented a lower ejection fraction (P = 0.013). Between these two groups, the incidence of post-OPCABG complications; the duration of intubation, ICU stay, and hospitalization; and the hospital expense did not differ. Notably, the ejection fraction was significantly negatively correlated with the duration of ICU stay and hospital expense. Conclusions Patients undergoing OPCABG with severe OSAHS are likely to exhibit a low ejection fraction and poor heart function, which may require a longer ICU stay and incur higher hospital expenses.
 
Patient selection and classification. The study population including 483 patients. Patients with REM-OSA were subdivided into three groups according to the definitions outlined below, and those that did not fall under REM-OSA 1 were defined as IND-OSA. REM OSA definition 1: AHI ≥ 5 and AHIREM/AHINREM ≥ 2. REM OSA definition 2: definition 1 with AHINREM < 15. REM OSA definition 3: definition 1 with AHINREM < 8 and REM sleep duration is ≥ 10.5 min
Article
Purpose The prevalence of rapid eye movement obstructive sleep apnea (REM-OSA) varies among reports. It remains unclear whether or not patients with REM-OSA experience more severe daytime sleepiness and poorer sleep quality than those with sleep-stage-independent obstructive sleep apnea (IND-OSA). We investigated the prevalence of REM-OSA in a Korean population sample and determined whether or not REM-OSA was associated with poor sleep quality and daytime sleepiness. Method In this retrospective study. we defined “REM-OSA 1” as an apnea–hypopnea index (AHI) ≥ 5 and AHIREM/AHINREM ratio ≥ 2. Patients who also had an AHINREM < 15 were classified as “REM-OSA 2” and those with an AHINREM < 8 and REM sleep duration ≥ 10.5 min were classified as “REM-OSA 3.” Patient characteristics, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and polysomnography variables were compared between the REM-OSA and IND-OSA groups. Results Among 483 patients, the prevalence rates of REM-OSA 1–3 were 10.3%, 5.5%, and 2.2% respectively. OSA severity was significantly lower in REM-OSA 1–3 than in IND-OSA. The proportion of women was significantly higher in REM-OSA 1–3 than IND-OSA groups. Patients with REM-OSA 2 and 3 had a significantly lower body mass index than those with IND-OSA. Patients with moderate-to-severe REM-OSA had significantly higher PSQI scores than those with IND-OSA. The AHIREM was significantly correlated with the ESS and PSQI scores. Conclusions Despite the relatively low prevalence and severity of REM-OSA, it may reduce sleep quality and increase daytime sleepiness in some patients.
 
Sleep-promoting protocol in the ICU
The relationship between noise levels and sleep quality
The incidence of delirium in the intervention and control groups
Article
Purpose This study aimed to evaluate the effect of a protocol of nonpharmacological interventions to improve sleep quality in the intensive care unit (ICU). Due to its close relationship with sleep quality, the effects of the same interventions on noise levels and delirium rates were also evaluated in this study. Methods This pretest–posttest design with a control group was carried out in a medical ICU over 8 months. Data were collected using Acute Physiology and Chronic Health Evaluation II, the Glasgow Coma Scale, the Richmond Agitation-Sedation Scale, the Richards-Campbell Sleep Questionnaire (RCSQ), the Confusion Assessment Method for the Intensive Care Unit, and noise measurement devices. In the first phase of the study, patients receiving standard care in the ICU were followed. After the first stage, a training session was held for nurses to raise awareness and information. Then, the sleep-promoting protocol created by the researchers was applied. The ambient noise level was measured continuously. Results A total of 78 patients with a mean age of 70.0 ± 13.2 years were followed in the ICU for an average of 7.3 ± 3.8 days. With protocol implementation, the ambient noise level in the ICU was reduced from 70.9 ± 3.8 dB(A) to 62.7 ± 3.5 dB(A) (p < 0.01); the RCSQ scores of the patients increased from 48.3 ± 1.4 to 62.1 ± 1.8 (p < 0.01). Although statistically nonsignificant, efforts to improve sleep quality also reduced the development of delirium by 15%. Conclusion It is possible to improve sleep quality and reduce noise levels in an ICU with a protocol consisting of multicomponent nonpharmacological interventions.
 
Article
Purpose Transcutaneous trigeminal electrical neuromodulation (TTEN) is a new treatment modality that has a potential to improve sleep through the suppression of noradrenergic activity. This study aimed to explore the changes of subjective and objective sleep parameters after 4-weeks of daily session of transcutaneous trigeminal electrical neuromodulation in a group of patients with insomnia. Methods In a group of patients with insomnia, TTEN targeting the ophthalmic division of the trigeminal nerve was utilized to test the effects of transcutaneous trigeminal electrical neuromodulation. Patients went through daily 20-min sessions of TTEN for 4 weeks. Polysomnography parameters, Pittsburgh sleep quality index, insomnia severity index, and Epworth sleepiness scale were obtained pre- and post-intervention. Changes in these parameters were compared and analyzed. Results Among 13 patients with insomnia there was a statistically significant reduction in Pittsburgh sleep quality index, insomnia severity index, and Epworth sleepiness scale scores after 4-week daily sessions of TTEN. There were no differences in polysomnography parameters pre- and post-intervention. Conclusion This is the first study to demonstrate the effects of TTEN in a group of insomnia patients. TTEN may improve subjective parameters in patients with insomnia. Further replication studies are needed to support this finding. Trial registration The data presented in the study are from a study exploring the effect of TTEN on insomnia (www.clinicaltrials.gov, registration number: NCT04838067, date of registration: April 8, 2021, “retrospectively registered”)
 
Respiratory pattern of a responder before and after HFNC treatment
Responses of AI and HI to HFNC. AI apnea index, HI hypopnea index, NREM nonrapid eye movement, REM rapid eye movement, AHI apnea hypopnea index
Distribution of ΔAI and ΔHI. In the nonresponder group, many patients had a decreased AI with HFNC; however, their HI increased with the therapy. For others, AI had slightly decreased or even increased (but only in three patients), but their HI have almost all decreased with HFNC therapy. Δ:the value off HFNC (baseline) minus the value on HFNC. ●ΔAI ○ΔHIAI: Apnea Index; HI: Hypopnea Index
Relationship of ΔAI and ΔHI. There was a negative correlation between the difference of AI and the difference of HI (Pearson’s test, r =  − 0.804, p = 0.000)
Distribution of ΔAHI in patients ≤ 50 years old and > 50 years old
Article
Purpose Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by the aggravation of upper airway constriction or obstruction, and it is associated with high incidence of various metabolic diseases and high mortality. Continuous positive airway pressure (CPAP) is now recommended as the first-line therapy for OSAHS, but its application is limited by its unsatisfactory patient tolerance. Previous studies have showed that high flow nasal cannula (HFNC) may improve symptoms in some patients with OSAHS. Therefore, the aim of the present study was to evaluate the effect of HFNC on OSAHS in a larger cohort than in previous research and to study the details of its therapeutic characteristics. Methods Polysomnography recording with and without HFNC was performed in 56 OSAHS patients with a wide spectrum of disease severity. Subgroups were divided by different treatment response criteria to identify the effect of this device. Results Of 56 patients enrolled, 9 were of mild severity (AHI, 5 to <15 events/h), 30 were of moderate severity (AHI, 15 to <30 events/h), and 17 patients were severe (AHI ≥ 30 events/h); 34 patients were younger than 50 years old and 22 patients were older than 50 years old. AHI decreased significantly (from 26.9 ± 14.7 to 21.5 ± 17.0 events/h, p < 0.001) after HFNC treatment in general. The subjects of responder group accounted for 21%. There was a negative correlation between the difference of AI and the difference of HI in nonresponder group before and after HFNC treatment, and the negative correlation was strong (Pearson’s test, r = − 0.804, p = 0.000). Of the patients with mild to moderate severity, 76% achieved any AHI reduction and 24% of patients achieved at least 50% reduction in AHI. Older patients (the age of responder group 52.6 ± 11.7 vs. nonresponder group 43.7 ± 12.1 years old, p < 0.05), especially patients older than 50 years, had a better response rate (≤ 50 years 9% vs. > 50 years 41%, p = 0.007). Conclusion HFNC may be useful in treating patients with OSAHS, especially older patients and those with mild to moderate severity. HFNC may be an alternative treatment when patients are intolerant of CPAP.
 
Top-cited authors
Ahmed S. Bahammam
  • King Saud University
Yong Won Cho
  • Keimyung University
Christian Guilleminault
  • Stanford University
Colin M Shapiro
  • University of Toronto
Nico de vries