Review and perspective on sleep-disordered breathing research and translation to clinics.

Sleep-disordered breathing, ranging from habitual snoring to severe obstructive sleep apnea, is a prevalent public health issue. Despite rising interest in sleep and awareness of sleep disorders, sleep research and diagnostic practices still rely on outdated metrics and laborious methods reducing the diagnostic capacity and preventing timely diagnosis and treatment. Consequently, a significant portion of individuals affected by sleep-disordered breathing remain undiagnosed or are misdiagnosed. Taking advantage of state-of-the-art scientific, technological, and computational advances could be an effective way to optimize the diagnostic and treatment pathways. We discuss state-of-the-art multidisciplinary research, review the shortcomings in the current practices of SDB diagnosis and management in adult populations, and provide possible future directions. We critically review the opportunities for modern data analysis methods and machine learning to combine multimodal information, provide a perspective on the pitfalls of big data analysis, and discuss approaches for developing analysis strategies that overcome current limitations. We argue that large-scale and multidisciplinary collaborative efforts based on clinical, scientific, and technical knowledge and rigorous clinical validation and implementation of the outcomes in practice are needed to move the research of sleep-disordered breathing forward, thus increasing the quality of diagnostics and treatment.

Multicentre sleep-stage scoring agreement in the Sleep Revolution project.

Determining sleep stages accurately is an important part of the diagnostic process for numerous sleep disorders. However, as the sleep stage scoring is done manually following visual scoring rules there can be considerable variation in the sleep staging between different scorers. Thus, this study aimed to comprehensively evaluate the inter-rater agreement in sleep staging. A total of 50 polysomnography recordings were manually scored by 10 independent scorers from seven different sleep centres. We used the 10 scorings to calculate a majority score by taking the sleep stage that was the most scored stage for each epoch. The overall agreement for sleep staging was κ = 0.71 and the mean agreement with the majority score was 0.86. The scorers were in perfect agreement in 48% of all scored epochs. The agreement was highest in rapid eye movement sleep (κ = 0.86) and lowest in N1 sleep (κ = 0.41). The agreement with the majority scoring varied between the scorers from 81% to 91%, with large variations between the scorers in sleep stage-specific agreements. Scorers from the same sleep centres had the highest pairwise agreements at κ = 0.79, κ = 0.85, and κ = 0.78, while the lowest pairwise agreement between the scorers was κ = 0.58. We also found a moderate negative correlation between sleep staging agreement and the apnea-hypopnea index, as well as the rate of sleep stage transitions. In conclusion, although the overall agreement was high, several areas of low agreement were also found, mainly between non-rapid eye movement stages.

Self-applied somnography: technical feasibility of electroencephalography and electro-oculography signal characteristics in sleep staging of suspected sleep-disordered adults.

Sleep recordings are increasingly being conducted in patients' homes where patients apply the sensors themselves according to instructions. However, certain sensor types such as cup electrodes used in conventional polysomnography are unfeasible for self-application. To overcome this, self-applied forehead montages with electroencephalography and electro-oculography sensors have been developed. We evaluated the technical feasibility of a self-applied electrode set from Nox Medical (Reykjavik, Iceland) through home sleep recordings of healthy and suspected sleep-disordered adults (n = 174) in the context of sleep staging. Subjects slept with a double setup of conventional type II polysomnography sensors and self-applied forehead sensors. We found that the self-applied electroencephalography and electro-oculography electrodes had acceptable impedance levels but were more prone to losing proper skin-electrode contact than the conventional cup electrodes. Moreover, the forehead electroencephalography signals recorded using the self-applied electrodes expressed lower amplitudes (difference 25.3%-43.9%, p < 0.001) and less absolute power (at 1-40 Hz, p < 0.001) than the polysomnography electroencephalography signals in all sleep stages. However, the signals recorded with the self-applied electroencephalography electrodes expressed more relative power (p < 0.001) at very low frequencies (0.3-1.0 Hz) in all sleep stages. The electro-oculography signals recorded with the self-applied electrodes expressed comparable characteristics with standard electro-oculography. In conclusion, the results support the technical feasibility of the self-applied electroencephalography and electro-oculography for sleep staging in home sleep recordings, after adjustment for amplitude differences, especially for scoring Stage N3 sleep.

Reaction time in psychomotor vigilance task is related to hypoxic load in males with sleep apnea.

Oxygen saturation (SpO2 )-based parameters are more strongly linked to impaired daytime vigilance than the conventional diagnostic metrics in patients with obstructive sleep apnea (OSA). However, whether the association between SpO2 -based parameters and impaired daytime vigilance is modulated by sex, remains unknown. Hence, we investigated the interplay between sex and detailed SpO2 -based metrics and their association with impaired vigilance in patients with OSA. The study population consisted of 855 (473 males, 382 females) patients with suspected OSA who underwent overnight polysomnography and psychomotor vigilance task (PVT). The population was grouped by sex and divided into quartiles (Q1-Q4) based on median reaction times (RTs) in the PVT. In addition to conventional diagnostic metrics, desaturation severity (DesSev), fall severity (FallSev), and recovery severity (RecovSev) were compared between the sexes and between the best (Q1) and worst (Q4) performing quartiles by using cumulative distribution functions (CDFs). Additionally, sex-specific covariate-adjusted linear regression models were used to investigate the connection between the parameters and RTs. The CDFs showed significantly higher hypoxic load in Q4 in males compared to females. In addition, the DesSev (ß = 8.05, p < 0.01), FallSev (ß = 6.48, p = 0.02), RecovSev (ß = 9.13, p < 0.01), and Oxygen Desaturation Index (ß = 12.29, p < 0.01) were associated with increased RTs only in males. Conversely, the Arousal Index (ß = 10.75-11.04, p < 0.01) was associated with impaired vigilance in females. The severity of intermittent hypoxaemia was strongly associated with longer RTs in males whereas the Arousal Index had the strongest association in females. Thus, the impact of hypoxic load on impaired vigilance seems to be stronger in males than females.

Multi-centre arousal scoring agreement in the Sleep Revolution.

We investigated arousal scoring agreement within full-night polysomnography in a multi-centre setting. Ten expert scorers from seven centres annotated 50 polysomnograms using the American Academy of Sleep Medicine guidelines. The agreement between arousal indexes (ArIs) was investigated using intraclass correlation coefficients (ICCs). Moreover, kappa statistics were used to evaluate the second-by-second agreement in whole recordings and in different sleep stages. Finally, arousal clusters, that is, periods with overlapping arousals by multiple scorers, were extracted. The overall similarity of the ArIs was fair (ICC = 0.41), varying from poor to excellent between the scorer pairs (ICC = 0.04-0.88). The ArI similarity was better in respiratory (ICC = 0.65) compared with spontaneous (ICC = 0.23) arousals. The overall second-by-second agreement was fair (Fleiss' kappa = 0.40), varying from poor to substantial depending on the scorer pair (Cohen's kappa = 0.07-0.68). Fleiss' kappa increased from light to deep sleep (0.45, 0.45, and 0.53 for stages N1, N2, and N3, respectively), was moderate in the rapid eye movement stage (0.48), and the lowest in the wake stage (0.25). Over a half of the arousal clusters were scored by one or two scorers, and less than a third by at least five scorers. In conclusion, the scoring agreement varied depending on the arousal type, sleep stage, and scorer pair, but was overall relatively low. The most uncertain areas were related to spontaneous arousals and arousals scored in the wake stage. These results indicate that manual arousal scoring is generally not reliable, and that changes are needed in the assessment of sleep fragmentation for clinical and research purposes.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Evaluating User Compliance in Mobile Health Apps: Insights from a 90-Day Study Using a Digital Sleep Diary.

Sleep diaries are the gold standard for subjective assessment of sleep variables in clinical practice. Digitization of sleep diaries is needed, as paper versions are prone to human error, memory bias, and difficulties monitoring compliance. METHODS: 45 healthy eligible participants (Mage = 50.3 years, range 23-74, 56% female) were asked to use a sleep diary mobile app for 90 consecutive days. Univariate and bivariate analysis was used for group comparison and linear regression for analyzing reporting trends and compliance over time. RESULTS: Overall compliance was high in the first two study months but tended to decrease over time (p < 0.001). Morning and evening diary entries were highly correlated (r = 0.932, p < 0.001) and participants significantly answered on average 4.1 days (95% CI [1.7, 6.6]) more often in the morning (M = 60.2, sd = 22.1) than evening ((M = 56.1, sd = 22.2), p < 0.001). CONCLUSION: Using a daily diary assessment in a longitudinal sleep study with a sleep diary delivered through a mobile application was feasible, and compliance in this study was satisfactory.

Deep learning-based algorithm accurately classifies sleep stages in preadolescent children with sleep-disordered breathing symptoms and age-matched controls.

Introduction: Visual sleep scoring has several shortcomings, including inter-scorer inconsistency, which may adversely affect diagnostic decision-making. Although automatic sleep staging in adults has been extensively studied, it is uncertain whether such sophisticated algorithms generalize well to different pediatric age groups due to distinctive EEG characteristics. The preadolescent age group (10-13-year-olds) is relatively understudied, and thus, we aimed to develop an automatic deep learning-based sleep stage classifier specifically targeting this cohort. Methods: A dataset (n = 115) containing polysomnographic recordings of Icelandic preadolescent children with sleep-disordered breathing (SDB) symptoms, and age and sex-matched controls was utilized. We developed a combined convolutional and long short-term memory neural network architecture relying on electroencephalography (F4-M1), electrooculography (E1-M2), and chin electromyography signals. Performance relative to human scoring was further evaluated by analyzing intra- and inter-rater agreements in a subset (n = 10) of data with repeat scoring from two manual scorers. Results: The deep learning-based model achieved an overall cross-validated accuracy of 84.1% (Cohen's kappa κ = 0.78). There was no meaningful performance difference between SDB-symptomatic (n = 53) and control subgroups (n = 52) [83.9% (κ = 0.78) vs. 84.2% (κ = 0.78)]. The inter-rater reliability between manual scorers was 84.6% (κ = 0.78), and the automatic method reached similar agreements with scorers, 83.4% (κ = 0.76) and 82.7% (κ = 0.75). Conclusion: The developed algorithm achieved high classification accuracy and substantial agreements with two manual scorers; the performance metrics compared favorably with typical inter-rater reliability between manual scorers and performance reported in previous studies. These suggest that our algorithm may facilitate less labor-intensive and reliable automatic sleep scoring in preadolescent children.

Consumer sleep technology for the screening of obstructive sleep apnea and snoring: current status and a protocol for a systematic review and meta-analysis of diagnostic test accuracy.

There are concerns about the validation and accuracy of currently available consumer sleep technology for sleep-disordered breathing. The present report provides a background review of existing consumer sleep technologies and discloses the methods and procedures for a systematic review and meta-analysis of diagnostic test accuracy of these devices and apps for the detection of obstructive sleep apnea and snoring in comparison with polysomnography. The search will be performed in four databases (PubMed, Scopus, Web of Science, and the Cochrane Library). Studies will be selected in two steps, first by an analysis of abstracts followed by full-text analysis, and two independent reviewers will perform both phases. Primary outcomes include apnea-hypopnea index, respiratory disturbance index, respiratory event index, oxygen desaturation index, and snoring duration for both index and reference tests, as well as the number of true positives, false positives, true negatives, and false negatives for each threshold, as well as for epoch-by-epoch and event-by-event results, which will be considered for the calculation of surrogate measures (including sensitivity, specificity, and accuracy). Diagnostic test accuracy meta-analyses will be performed using the Chu and Cole bivariate binomial model. Mean difference meta-analysis will be performed for continuous outcomes using the DerSimonian and Laird random-effects model. Analyses will be performed independently for each outcome. Subgroup and sensitivity analyses will evaluate the effects of the types (wearables, nearables, bed sensors, smartphone applications), technologies (e.g., oximeter, microphone, arterial tonometry, accelerometer), the role of manufacturers, and the representativeness of the samples.

Obstructive sleep apnea-related intermittent hypoxaemia is associated with impaired vigilance.

Obstructive sleep apnea (OSA)-related intermittent hypoxaemia is a potential risk factor for different OSA comorbidities, for example cardiovascular disease. However, conflicting results are found as to whether intermittent hypoxaemia is associated with impaired vigilance. Therefore, we aimed to investigate how desaturation characteristics differ between the non-impaired vigilance and impaired vigilance patient groups formed based on psychomotor vigilance task (PVT) performance and compared with traditional OSA severity parameters. The study population comprised 863 patients with suspected OSA who underwent a PVT test before polysomnography. The conventional OSA parameters, for example, the apnea-hypopnea index, oxygen desaturation index, and arousal index were computed. Furthermore, the median desaturation area, fall area, recovery area, and desaturation depth were computed with the pre-event baseline reference and with reference to the 100% oxygen saturation level. Patients were grouped into best- and worst-performing quartiles based on the number of lapses in PVT (Q1: PVT lapses <5 and Q4: PVT lapses >36). The association between parameters and impaired vigilance was evaluated by cumulative distribution functions (CDFs) and binomial logistic regression. Based on the CDFs, patients in Q4 had larger desaturation areas, recovery areas, and deeper desaturations when these were referenced to 100% saturation compared with Q1. The odds ratio (OR) of the median desaturation area (OR = 1.56), recovery area (OR = 1.71), and depth (OR = 1.65) were significantly elevated in Q4 in regression models. However, conventional OSA parameters were not significantly associated with impaired vigilance (ORs: 0.79-1.09). Considering desaturation parameters with a 100% SpO2 reference in the diagnosis of OSA could provide additional information on the severity of OSA and related daytime vigilance impairment.

A-phase index: an alternative view for sleep stability analysis based on automatic detection of the A-phases from the cyclic alternating pattern.

STUDY OBJECTIVES: Sleep stability can be studied by evaluating the cyclic alternating pattern (CAP) in electroencephalogram (EEG) signals. The present study presents a novel approach for assessing sleep stability, developing an index based on the CAP A-phase characteristics to display a sleep stability profile for a whole night's sleep. METHODS: Two ensemble classifiers were developed to automatically score the signals, one for "A-phase" and the other for "non-rapid eye movement" estimation. Both were based on three one-dimension convolutional neural networks. Six different inputs were produced from the EEG signal to feed the ensembles' classifiers. A proposed heuristic-oriented search algorithm individually tuned the classifiers' structures. The outputs of the two ensembles were combined to estimate the A-phase index (API). The models can also assess the A-phase subtypes, their API, and the CAP cycles and rate. RESULTS: Four dataset variations were considered, examining healthy and sleep-disordered subjects. The A-phase average estimation's accuracy, sensitivity, and specificity range was 82%-87%, 72%-80%, and 82%-88%, respectively. A similar performance was attained for the A-phase subtype's assessments, with an accuracy range of 82%-88%. Furthermore, in the examined dataset's variations, the API metric's average error varied from 0.15 to 0.25 (with a median range of 0.11-0.24). These results were attained without manually removing wake or rapid eye movement periods, leading to a methodology suitable to produce a fully automatic CAP scoring algorithm. CONCLUSIONS: Metrics based on API can be understood as a new view for CAP analysis, where the goal is to produce and examine a sleep stability profile.

The European Sleep Research Society - past, present and future.

It is 50 years ago, in 1972, that the founding conference of the European Sleep Research Society (ESRS) was organised in Basel. Since then the Society has had 13 presidents and a multitude of board members and has organised, among other things, another 24 congresses. At this 50th anniversary, as the 26th ESRS congress is approaching, we have summarised the history of the ESRS. In this review, we provide a background to show why the foundation of a European society was a logical step, and show how, in the course of the past 50 years, the Society changed and grew. We give special attention to some developments that occurred over the years and discuss where the ESRS stands now, and how we foresee its future.

Novel oxygen desaturation parameters are associated with cardiac troponin I: Data from the Akershus Sleep Apnea Project.

Novel diagnostic markers for obstructive sleep apnea beyond the apnea-hypopnea index (AHI) have been introduced. There are no studies on their association with markers of subclinical myocardial injury. We assessed the association between novel desaturation parameters and elevated cardiac troponin I and T. Participants with polysomnography (498) from the Akershus Sleep Apnea study were divided into normal and elevated biomarker groups based on sex-specific concentration thresholds (cardiac troponin I: ≥4 ng/L for women, ≥6 ng/L for men; and cardiac troponin T: ≥7 ng/L for women, ≥8 ng/L for men). Severity of obstructive sleep apnea was evaluated with the AHI, oxygen desaturation index, total sleep time with oxygen saturation below 90% (T90), lowest oxygen saturation (Min SpO2 %), and novel oxygen desaturation parameters: desaturation duration and desaturation severity. How the AHI and novel desaturation parameters predicted elevated cardiac troponin I and cardiac troponin T levels was assessed by the area under the curve (AUC). Based on multivariable-adjusted linear regression, the AHI (ß = 0.004, p = 0.012), desaturation duration (ß = 0.007, p = 0.004), and desaturation severity (ß = 0.147, p = 0.002) were associated with cardiac troponin I levels but not cardiac troponin T. T90 was associated with cardiac troponin I (ß = 0.006, p = 0.009) and cardiac troponin T (ß = 0.005, p = 0.007). The AUC for the AHI 0.592 (standard error 0.043) was not significantly different from the AUC of T90 (SD 0.640, p = 0.08), desaturation duration 0.609 (SD 0.044, p = 0.42) or desaturation severity 0.616 (SD 0.043, p = 0.26) in predicting myocardial injury as assessed by cardiac troponin I. Oxygen desaturation parameters and the AHI were associated with cardiac troponin I levels but not cardiac troponin T levels. Novel oxygen desaturation parameters did not improve the prediction of subclinical myocardial injury compared to the AHI.

Importance of Getting Enough Sleep and Daily Activity Data to Assess Variability: Longitudinal Observational Study.

BACKGROUND: The gold standard measurement for recording sleep is polysomnography performed in a hospital environment for 1 night. This requires individuals to sleep with a device and several sensors attached to their face, scalp, and body, which is both cumbersome and expensive. Self-trackers, such as wearable sensors (eg, smartwatch) and nearable sensors (eg, sleep mattress), can measure a broad range of physiological parameters related to free-living sleep conditions; however, the optimal duration of such a self-tracker measurement is not known. For such free-living sleep studies with actigraphy, 3 to 14 days of data collection are typically used. OBJECTIVE: The primary goal of this study is to investigate if 3 to 14 days of sleep data collection is sufficient while using self-trackers. The secondary goal is to investigate whether there is a relationship among sleep quality, physical activity, and heart rate. Specifically, we study whether individuals who exhibit similar activity can be clustered together and to what extent the sleep patterns of individuals in relation to seasonality vary. METHODS: Data on sleep, physical activity, and heart rate were collected over 6 months from 54 individuals aged 52 to 86 years. The Withings Aura sleep mattress (nearable; Withings Inc) and Withings Steel HR smartwatch (wearable; Withings Inc) were used. At the individual level, we investigated the consistency of various physical activities and sleep metrics over different time spans to illustrate how sensor data from self-trackers can be used to illuminate trends. We used exploratory data analysis and unsupervised machine learning at both the cohort and individual levels. RESULTS: Significant variability in standard metrics of sleep quality was found between different periods throughout the study. We showed specifically that to obtain more robust individual assessments of sleep and physical activity patterns through self-trackers, an evaluation period of >3 to 14 days is necessary. In addition, we found seasonal patterns in sleep data related to the changing of the clock for daylight saving time. CONCLUSIONS: We demonstrate that >2 months' worth of self-tracking data are needed to provide a representative summary of daily activity and sleep patterns. By doing so, we challenge the current standard of 3 to 14 days for sleep quality assessment and call for the rethinking of standards when collecting data for research purposes. Seasonal patterns and daylight saving time clock change are also important aspects that need to be taken into consideration when choosing a period for collecting data and designing studies on sleep. Furthermore, we suggest using self-trackers (wearable and nearable ones) to support longer-term evaluations of sleep and physical activity for research purposes and, possibly, clinical purposes in the future.

Improving Machine Learning Technology in the Field of Sleep.

The authors discuss the challenges of machine- and deep learning-based automatic analysis of obstructive sleep apnea with respect to known issues with the signal interpretation, patient physiology, and the apnea-hypopnea index. Their goal is to provide guidance for sleep and machine learning professionals working in this area of sleep medicine. They suggest that machine learning approaches may well be better targeted at examining and attempting to improve the diagnostic criteria, in order to build a more nuanced understanding of the detailed circumstances surrounding OSA, rather than merely attempting to reproduce human scoring.

The Future of Sleep Measurements: A Review and Perspective.

This article provides an overview of the current use, limitations, and future directions of the variety of subjective and objective sleep assessments available. This article argues for various ways and sources of collecting, combining, and using data to enlighten clinical practice and the sleep research of the future. It highlights the prospects of digital management platforms to store and present the data, and the importance of codesign when developing such platforms and other new instruments. It also discusses the abundance of opportunities that data science and machine learning open for the analysis of data.

Sleep medicine catalogue of knowledge and skills - Revision.

The 'catalogue of knowledge and skills' for sleep medicine presents the blueprint for a curriculum, a textbook, and an examination on sleep medicine. The first catalogue of knowledge and skills was presented by the European Sleep Research Society in 2014. It was developed following a formal Delphi procedure. A revised version was needed in order to incorporate changes that have occurred in the meantime in the International Classification of Sleep Disorders, updates in the manual for scoring sleep and associated events, and, most important, new knowledge in sleep physiology and pathophysiology. In addition, another major change can be observed in sleep medicine: a paradigm shift in sleep medicine has taken place. Sleep medicine is no longer a small interdisciplinary field in medicine. Sleep medicine has increased in terms of recognition and importance in medical care. Consequently, major medical fields (e.g. pneumology, cardiology, neurology, psychiatry, otorhinolaryngology, paediatrics) recognise that sleep disorders become a necessity for education and for diagnostic assessment in their discipline. This paradigm change is considered in the catalogue of knowledge and skills revision by the addition of new chapters.