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Keywords = sleep-disordered breathing (SDB)

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17 pages, 1738 KiB  
Article
Multimodal Fusion Multi-Task Learning Network Based on Federated Averaging for SDB Severity Diagnosis
by Songlu Lin, Renzheng Tang, Yuzhe Wang and Zhihong Wang
Appl. Sci. 2025, 15(14), 8077; https://doi.org/10.3390/app15148077 - 20 Jul 2025
Viewed by 524
Abstract
Accurate sleep staging and sleep-disordered breathing (SDB) severity prediction are critical for the early diagnosis and management of sleep disorders. However, real-world polysomnography (PSG) data often suffer from modality heterogeneity, label scarcity, and non-independent and identically distributed (non-IID) characteristics across institutions, posing significant [...] Read more.
Accurate sleep staging and sleep-disordered breathing (SDB) severity prediction are critical for the early diagnosis and management of sleep disorders. However, real-world polysomnography (PSG) data often suffer from modality heterogeneity, label scarcity, and non-independent and identically distributed (non-IID) characteristics across institutions, posing significant challenges for model generalization and clinical deployment. To address these issues, we propose a federated multi-task learning (FMTL) framework that simultaneously performs sleep staging and SDB severity classification from seven multimodal physiological signals, including EEG, ECG, respiration, etc. The proposed framework is built upon a hybrid deep neural architecture that integrates convolutional layers (CNN) for spatial representation, bidirectional GRUs for temporal modeling, and multi-head self-attention for long-range dependency learning. A shared feature extractor is combined with task-specific heads to enable joint diagnosis, while the FedAvg algorithm is employed to facilitate decentralized training across multiple institutions without sharing raw data, thereby preserving privacy and addressing non-IID challenges. We evaluate the proposed method across three public datasets (APPLES, SHHS, and HMC) treated as independent clients. For sleep staging, the model achieves accuracies of 85.3% (APPLES), 87.1% (SHHS_rest), and 79.3% (HMC), with Cohen’s Kappa scores exceeding 0.71. For SDB severity classification, it obtains macro-F1 scores of 77.6%, 76.4%, and 79.1% on APPLES, SHHS_rest, and HMC, respectively. These results demonstrate that our unified FMTL framework effectively leverages multimodal PSG signals and federated training to deliver accurate and scalable sleep disorder assessment, paving the way for the development of a privacy-preserving, generalizable, and clinically applicable digital sleep monitoring system. Full article
(This article belongs to the Special Issue Machine Learning in Biomedical Applications)
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15 pages, 1110 KiB  
Review
Sleep-Disordered Breathing and Interactions with Opioids: A Narrative Review
by Peyton J. Murin, Jora Wang and Yuri Chaves Martins
J. Clin. Med. 2025, 14(13), 4758; https://doi.org/10.3390/jcm14134758 - 4 Jul 2025
Viewed by 674
Abstract
Opioid use in patients with sleep disordered breathing (SDB) presents therapeutic challenges within chronic pain and sleep medicine. Opioids impair respiratory drive through μ-opioid receptor activation in brainstem respiratory centers, exacerbating both obstructive and central apneas. Chronic opioid use is also linked to [...] Read more.
Opioid use in patients with sleep disordered breathing (SDB) presents therapeutic challenges within chronic pain and sleep medicine. Opioids impair respiratory drive through μ-opioid receptor activation in brainstem respiratory centers, exacerbating both obstructive and central apneas. Chronic opioid use is also linked to a high prevalence of central sleep apnea and increased nocturnal hypoventilation. Simultaneously, SDB contributes to heightened pain sensitivity via intermittent hypoxia, systemic inflammation, and alterations in neural plasticity. These mechanisms may influence opioid efficacy and dosing requirements. This review summarizes current evidence on how SDB and opioid use interact, emphasizing chronic opioid use in the setting of chronic pain management. We discuss the underlying mechanisms, clinical impacts, and potential avenues for enhanced diagnosis and therapy in this population. We conclude that the intersection of SDB and opioid use presents a complex clinical challenge that demands a multidisciplinary approach. Enhanced screening, personalized pharmacologic strategies, and integration of advanced diagnostics are essential for mitigating risks and optimizing care. Future research should focus on mechanistic studies and interventional trials to guide evidence-based management of this high-risk population. Full article
(This article belongs to the Section Anesthesiology)
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12 pages, 274 KiB  
Article
Sleep Disturbances and Obstructive Sleep Apnea in Children and Adolescents with Cerebral Palsy: An Observational Study
by Isabella Meneses da Silva, Maria Clara Helena do Couto, Sanseray da Silveira Cruz-Machado, Leticia Monteiro de Andrade, Ana Elisa Zuliani Stroppa Marques, Celia Maria Giacheti, Cristiane Rodrigues Pedroni and Luciana Pinato
Neurol. Int. 2025, 17(7), 101; https://doi.org/10.3390/neurolint17070101 - 30 Jun 2025
Viewed by 338
Abstract
Background/Objectives: Cerebral palsy (CP) is a neurodevelopmental disorder associated with sleep disturbances, particularly sleep-disordered breathing (SDB), and is often linked to an increased risk of obstructive sleep apnea (OSA). OSA is underdiagnosed in this population due to the lack of standardized methods and [...] Read more.
Background/Objectives: Cerebral palsy (CP) is a neurodevelopmental disorder associated with sleep disturbances, particularly sleep-disordered breathing (SDB), and is often linked to an increased risk of obstructive sleep apnea (OSA). OSA is underdiagnosed in this population due to the lack of standardized methods and limited access to appropriate diagnostic technologies and appropriate equipment. Thus, this study aimed to investigate the presence and severity of sleep disorders, with a particular focus on OSA, in children and adolescents with CP compared to their typically developing peers. Methods: This observational, clinical, and prospective study included 28 children and adolescents with CP and 32 age- and sex-matched typically developing individuals. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (SDSC) and a high-resolution oximeter plus actigraphy combined with a cloud-based algorithm for the detection of obstructive sleep apnea (Biologix® system), which provided data on oxygen saturation, snoring, movement during sleep, and total sleep time. Results: According to the SDSC, 92% of children and adolescents with CP presented scores indicative of sleep disturbances, compared to 31% of typically developing individuals. SDB was the most prevalent subtype (64%) and overnight oximetry revealed that 100% of the CP group presented oxygen desaturation index (ODI) values consistent with a diagnosis of OSA. The CP group also exhibited significantly lower mean SpO2, longer snoring duration, shorter total sleep time, and prolonged sleep latency compared to the typically developing group. Conclusions: Children and adolescents with cerebral palsy (CP) exhibit a high prevalence of sleep disturbances, with increasing evidence indicating a significant occurrence of sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA). Full article
17 pages, 670 KiB  
Article
Effects of Oral Appliance Therapy with a Mouth Shield in Periodontitis Patients Who Snore: A Split-Mouth Randomized Controlled Trial
by Ju-Ying Lin, Emet Schneiderman, Jason Hui, Carlos Parra Carrasquer, William Stenberg, Zohre German, Jason Adam Harvey and Preetam Schramm
Dent. J. 2025, 13(7), 292; https://doi.org/10.3390/dj13070292 - 27 Jun 2025
Viewed by 338
Abstract
Background: Periodontitis is linked to sleep-disordered breathing (SDB), including snoring, with 50–75% of cases involving mouth breathing (MB). Standard treatment includes scaling and root planing (SRP). Oral appliance therapy (OAT) is used to treat snoring and SDB. OAT plus a mouth shield [...] Read more.
Background: Periodontitis is linked to sleep-disordered breathing (SDB), including snoring, with 50–75% of cases involving mouth breathing (MB). Standard treatment includes scaling and root planing (SRP). Oral appliance therapy (OAT) is used to treat snoring and SDB. OAT plus a mouth shield (OAT+) worn during sleep may reduce MB to enhance periodontal health. This study evaluated whether OAT+, as an adjunct to SRP, improves periodontal health by reducing periodontal pathogens and facilitating upper airway patency. Methods: Fourteen participants with mild–moderate periodontitis were randomized to receive SRP on one side of the mouth at baseline (T0). Pocket depth (PD), bleeding on probing (BOP), and plaque index (PI) were recorded, and bacterial DNA from periodontal pockets were analyzed via PCR at baseline (T0) and 12 weeks (T3). At 4 weeks (T1), all participants received a self-titrated myTAP® OA, followed by a mouth shield at 8 weeks (T2). Sleep metrics, including respiratory disturbance index (RDI), were recorded using the NOX T3 at T0–T3. Results: BOP and deep PD levels exhibited slight improvements from the baseline for both SRP and non-SRP (OAT+ only) treated sites but did not achieve significance. BOP decreased significantly more from the baseline in the SRP than in the non-SRP group at T3 (p = 0.028); P. gingivalis’ presence declined on both sides (p = 0.0135). Other periodontal and bacterial parameters showed no significant differences between or within groups. Snoring (p = 0.011), MB (p = 0.025), and RDI (p = 0.019) significantly decreased with OAT+ at T3. Conclusions: In mild–moderate periodontitis patients who snore, OAT+ reduces snoring, MB, and obstructive events, serving as an adjunct to SRP with no negative clinical effects over the short term. The combined therapy yielded similar results to OAT+ alone, likely due to minimization of MB. Its capacity to improve the oral environment is worthy of further investigation. Full article
(This article belongs to the Special Issue Dentistry in the 21st Century: Challenges and Opportunities)
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7 pages, 398 KiB  
Article
Evaluating Obstructive Sleep Apnea Utilizing Arterial Tonometry in Individuals with Cystic Fibrosis
by Michelle Chiu, Bethany Bartley, Elizabeth Gootkind, Salma Batool-Anwar, Donald G. Keamy, Thomas Bernard Kinane, Lael M. Yonker and Kevin S. Gipson
Adv. Respir. Med. 2025, 93(3), 20; https://doi.org/10.3390/arm93030020 - 17 Jun 2025
Viewed by 451
Abstract
Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific [...] Read more.
Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific recommendations available to help clinicians identify patients with CF who are at increased risk of sleep disorders. Home sleep apnea testing using a validated peripheral arterial tonometry (PAT) device may offer an accurate diagnosis of OSA in a more convenient and low-cost method than in-lab polysomnography. In this single-center study of 19 adults with CF, we found an increased prevalence of OSA among individuals with CF compared to general population estimates. Although associations with an FEV < 70% predicted and a modified Mallampati score ≥ 3 were observed, these odds ratios did not reach statistical significance, likely reflecting limited power in this small pilot sample. There was no association found between the self-reported presence of nocturnal cough or snoring and OSA. We also found no association between OSA and abnormal scores on commonly used, validated sleep questionnaires, suggesting that CF-specific scales may be needed for effective screening in the CF clinic. Full article
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12 pages, 602 KiB  
Article
Effects of SGLT2 Inhibitors on Sleep Apnea Parameters and Cheyne–Stokes Respiration in Patients with Acute Decompensated Heart Failure: A Prospective Cohort Study
by Petar Kalaydzhiev, Tsvetelina Velikova, Yanitsa Davidkova, Gergana Voynova, Angelina Borizanova, Natalia Spasova, Neli Georgieva, Radostina Ilieva, Elena Kinova and Assen Goudev
Biomedicines 2025, 13(6), 1474; https://doi.org/10.3390/biomedicines13061474 - 14 Jun 2025
Viewed by 642
Abstract
Background: Sleep-disordered breathing (SDB), particularly Cheyne–Stokes respiration (CSR), is highly prevalent among patients hospitalized with acute decompensated heart failure (ADHF) and is associated with worse clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in heart failure, but their effects on nocturnal [...] Read more.
Background: Sleep-disordered breathing (SDB), particularly Cheyne–Stokes respiration (CSR), is highly prevalent among patients hospitalized with acute decompensated heart failure (ADHF) and is associated with worse clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in heart failure, but their effects on nocturnal respiratory parameters remain underexplored. Objectives: This study aims to evaluate the impact of SGLT2i therapy on key respiratory and cardiac indices including CSR burden, oxygenation, and right heart function in patients with ADHF and reduced left ventricular ejection fraction. Methods: In this single-center prospective cohort study, 60 patients with ADHF, LVEF < 40%, and a baseline apnea–hypopnea index (AHI) > 5 were assessed before and three months after the initiation of SGLT2i therapy. Sleep respiratory parameters were measured using home polygraphy (ApneaLinkTM), while cardiac and renal indices were evaluated by echocardiography, NT-proBNP, and the estimated glomerular filtration rate (eGFR). Structural and functional echocardiographic changes were analyzed both at baseline and following the 3-month treatment period. Patient-reported outcomes were assessed using the Epworth Sleepiness Scale (ESS) and Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: After 3 months of SGLT2i therapy, significant improvements were observed in daytime sleepiness (ESS: −2.68 points; p < 0.001), CSR index (−5.63 events/h; p < 0.001), AHI (−3.07 events/h; p < 0.001), ODI (−6.11 events/h; p < 0.001), and mean nocturnal SpO2 (+1.95%; p < 0.001). KCCQ scores increased by 9.16 points (p < 0.001), indicating improved quality of life. Cardiac assessments revealed reductions in NT-proBNP (−329.6 pg/mL; p < 0.001) and E/e′ ratio (−1.08; p < 0.001), with no significant change in LVEF or chamber dimensions. Right ventricular function improved, as evidenced by the increased TAPSE/sPAP ratio (+0.018; p < 0.001). Renal function remained stable, with a non-significant upward trend in eGFR. Conclusions: This exploratory study suggests that SGLT2 inhibitors may be associated with the attenuation of Cheyne–Stokes respiration and an improvement in right heart function in patients with ADHF, warranting further investigation in controlled trials. These findings highlight the potential of SGLT2is to address overlapping cardio-respiratory dysfunction in this high-risk population. Full article
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17 pages, 5336 KiB  
Article
AttenCRF-U: Joint Detection of Sleep-Disordered Breathing and Leg Movements in OSA Patients
by Qiuyue Li, Kewei Li, Cong Fu, Yiyuan Zhang, Huan Yu, Chen Chen and Wei Chen
Bioengineering 2025, 12(6), 571; https://doi.org/10.3390/bioengineering12060571 - 26 May 2025
Viewed by 473
Abstract
Obstructive sleep apnea (OSA) is characterized by frequent episodes of sleep-disordered breathing (SDB), which are often accompanied by leg movement (LM) events, especially periodic limb movements during sleep (PLMS). Traditional single-event detection methods often overlook the dynamic interactions between SDB and LM, failing [...] Read more.
Obstructive sleep apnea (OSA) is characterized by frequent episodes of sleep-disordered breathing (SDB), which are often accompanied by leg movement (LM) events, especially periodic limb movements during sleep (PLMS). Traditional single-event detection methods often overlook the dynamic interactions between SDB and LM, failing to capture their temporal overlap and differences in duration. To address this, we propose Attention-enhanced CRF with U-Net (AttenCRF-U), a novel joint detection framework that integrates multi-head self-attention (MHSA) within an encoder–decoder architecture to model long-range dependencies between overlapping events and employs multi-scale convolutional encoding to extract discriminative features across different temporal scales. The model further incorporates a conditional random field (CRF) to refine event boundaries and enhance temporal continuity. Evaluated on clinical PSG recordings from 125 OSA patients, the model with CRF improved the average F1 score from 0.782 to 0.788 and reduced temporal alignment errors compared with CRF-free baselines. The joint detection strategy distinguished respiratory-related leg movements (RRLMs) from PLMS, boosting the PLMS detection F1 score from 0.756 to 0.778 and the SDB detection F1 score from 0.709 to 0.728. By integrating MHSA into a CRF-augmented U-Net framework and enabling joint detection of multiple event types, this study presents a novel approach to modeling temporal dependencies and event co-occurrence patterns in sleep disorder diagnosis. Full article
(This article belongs to the Section Biosignal Processing)
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24 pages, 1860 KiB  
Systematic Review
Sleep-Disordered Breathing and Hypertension—A Systematic Review
by Ayman Battisha, Amrit Kahlon and Dinesh K. Kalra
J. Clin. Med. 2025, 14(9), 3115; https://doi.org/10.3390/jcm14093115 - 30 Apr 2025
Viewed by 1206
Abstract
Background/Objectives: Sleep-disordered breathing (SDB), historically referred to as “sleep apnea syndrome”, particularly obstructive sleep apnea (OSA), is an independent risk factor for hypertension (HTN), stroke, heart failure, arrhythmias, and other cardiovascular disorders. Despite the well-established link between OSA and HTN and its high [...] Read more.
Background/Objectives: Sleep-disordered breathing (SDB), historically referred to as “sleep apnea syndrome”, particularly obstructive sleep apnea (OSA), is an independent risk factor for hypertension (HTN), stroke, heart failure, arrhythmias, and other cardiovascular disorders. Despite the well-established link between OSA and HTN and its high occurrence in cardiovascular disorders, the focus on the complex OSA–HTN axis is often overlooked or inadequately managed, which might explain the lack of notable improvements in cardiovascular outcomes for this patient population. Understanding the complex relationship between OSA and HTN is crucial due to its significant implications for clinical practice and public health. Methods: Using an expanded list of relevant MeSH terms, including “sleep-disordered breathing” and “sleep apnea syndrome”, and following the PRISMA model, peer-reviewed articles were systematically selected. Studies published from January 2000 through December 2024 were identified and screened based on predefined inclusion and exclusion criteria. Results: This review emphasizes both OSA’s independent and interaction effects on cardiovascular health and outcomes across different populations. It identifies key factors mediating the association between OSA and HTN. Conclusions: Multimodal management, including continuous positive airway pressure and lifestyle modification, is essential for treating hypertension related to OSA. Effective management of the OSA–HTN relationship is vital to improving cardiovascular outcomes. Full article
(This article belongs to the Section Cardiovascular Medicine)
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9 pages, 211 KiB  
Article
The Role of Polysomnography for Children with Attention-Deficit/Hyperactivity Disorder
by Chien-Heng Lin, Po-Yen Wu, Syuan-Yu Hong, Yu-Tzu Chang, Sheng-Shing Lin and I-Ching Chou
Life 2025, 15(4), 678; https://doi.org/10.3390/life15040678 - 21 Apr 2025
Viewed by 805
Abstract
Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsive behavior. In recent years, studies have shown that patients with ADHD often experience sleep problems, raising clinical interest in the potential role of polysomnography (PSG) in [...] Read more.
Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsive behavior. In recent years, studies have shown that patients with ADHD often experience sleep problems, raising clinical interest in the potential role of polysomnography (PSG) in the diagnosis and management of ADHD. This study examines polysomnographic findings in children with ADHD who present with diverse sleep complaints. Methods: A cohort of children aged younger than 18 years, diagnosed with ADHD based on DSM-5 criteria, underwent overnight polysomnography. The study assessed various sleep parameters, including sleep latency, sleep efficiency, total sleep time, and the presence of sleep-disordered breathing. Results: A retrospective analysis was conducted on 36 children (29 boys and 7 girls) aged 6 to 14 years, diagnosed with ADHD, who underwent polysomnography between 2021 and 2024. Polysomnographic findings revealed that 77.78% of the children demonstrated significant snoring. Furthermore, 50.0% were diagnosed with obstructive sleep apnea syndrome (OSAS). In addition, eight children exhibited parasomnias. Among them, six had bruxism, three were diagnosed with periodic limb movement disorder (PLMD), and two experienced sleep talking. Other notable sleep-related conditions included two cases of narcolepsy, one case of prolonged sleep onset latency, and one case of central apnea syndrome. Total sleep time (TST) was significantly longer in females compared to males (400.71 ± 32.68 min vs. 361.24 ± 41.20 min, p = 0.0215), whereas rapid eye movement (REM) latency was longer in males compared to females (118.62 ± 55.60 min vs. 78.57 ± 27.82 min, p = 0.0194). These findings highlight the high prevalence of sleep-disordered breathing (SDB) in children with ADHD who present with sleep disturbances. Furthermore, sleep quality, as indicated by longer TST and shorter REM latency, appears to be better in females with ADHD. Conclusions: The findings of this study underscore the critical role of polysomnography (PSG) in the assessment of children with ADHD. PSG provides an objective evaluation of sleep abnormalities commonly associated with ADHD, which may influence symptom manifestation and treatment outcomes. Notably, the results suggest that females with ADHD exhibit better sleep quality, as indicated by longer total sleep time (TST) and shorter rapid eye movement (REM) latency compared to males. We recommend incorporating polysomnography (PSG) into the comprehensive assessment of children with ADHD who present with significant sleep disturbances. Further research is warranted to investigate the impact of targeted interventions for sleep abnormalities on ADHD symptoms, prognosis, and potential sex-specific differences. Full article
15 pages, 886 KiB  
Article
Evaluation of Sleep-Disordered Breathing and Respiratory Dysfunction in Children with Myotonic Dystrophy Type 1—A Retrospective Cross-Sectional Study
by Mihail Basa, Jovan Pesovic, Dusanka Savic-Pavicevic, Stojan Peric, Giovanni Meola, Alessandro Amaddeo, Gordana Kovacevic, Slavica Ostojic and Aleksandar Sovtic
Biomedicines 2025, 13(4), 966; https://doi.org/10.3390/biomedicines13040966 - 15 Apr 2025
Viewed by 899
Abstract
Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disorder characterized by respiratory dysfunction that significantly impacts quality of life and longevity. This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with [...] Read more.
Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disorder characterized by respiratory dysfunction that significantly impacts quality of life and longevity. This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with DM1 and to identify the factors contributing to SDB. Methods: A retrospective study examined patients’ medical records, including genetic analyses, clinical characteristics, and noninvasive pulmonary function testing (PFT), when possible. The Pediatric Sleep Questionnaire (PSQ), arterial blood gases, polygraphy, and overnight transcutaneous capnometry (PtcCO2) were used to assess SDB. Results: The size of CTG expansion in the DMPK gene directly correlated with the severity of respiratory complications and the need for early tracheostomy tube insertion in 7/20 (35%) patients. A total of 13/20 (65%) children were available for respiratory evaluation during spontaneous breathing. While moderate/severe obstructive sleep apnea syndrome (OSAS) and hypoventilation were confirmed in 4/13 (31%) children, none of the patients had mixed or dominantly central sleep apnea syndrome. There was no correlation between apnea–hypopnea index (AHI) or PtcCO2 and the presence of SDB-related symptoms or the PSQ score. Although a significant correlation between AHI and PtcCO2 was not confirmed (p = 0.447), the oxygen desaturation index directly correlated with PtcCO2 (p = 0.014). Conclusions: While SDB symptoms in children with DM1 may not fully correlate with observed respiratory events or impaired gas exchange during sleep, a comprehensive screening for SDB should be considered for all patients with DM1. Further research into disease-specific recommendations encompassing the standardization of PFT, as well as overnight polygraphic and capnometry recordings, could help to guide timely, personalized treatment. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of Muscular Dystrophy)
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18 pages, 1883 KiB  
Article
Increased Myocardial MARK4 Expression in Patients with Heart Failure and Sleep-Disordered Breathing
by Bettina Seydel, Philipp Hegner, Anna-Maria Lauerer, Sönke Schildt, Fatma Bayram, Maria Tafelmeier, Dominik Wermers, Leopold Rupprecht, Christof Schmid, Stefan Wagner, Lars Siegfried Maier, Michael Arzt and Simon Lebek
Int. J. Mol. Sci. 2025, 26(8), 3614; https://doi.org/10.3390/ijms26083614 - 11 Apr 2025
Viewed by 602
Abstract
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic targets and strategies. The kinase MARK4 (MAP (microtubule-associated proteins)/microtubule affinity-regulating kinase 4) regulates microtubule-associated proteins pivotal for cell polarity, protein stability, and intracellular signaling. Animal [...] Read more.
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic targets and strategies. The kinase MARK4 (MAP (microtubule-associated proteins)/microtubule affinity-regulating kinase 4) regulates microtubule-associated proteins pivotal for cell polarity, protein stability, and intracellular signaling. Animal models of heart failure revealed elevated MARK4 levels, which correlated with impaired cardiac contractility. However, the involvement of MARK4 and its potential as a molecular drug target has not yet been explored in the myocardium of cardiovascular patients. We investigated the MARK4 mRNA expression in human myocardial biopsies of 152 high-risk cardiovascular patients undergoing cardiac surgery. Comprehensive echocardiography as well as testing for sleep-disordered breathing (SDB), a critical comorbidity in heart failure, were assessed preoperatively. We observed a substantial upregulation of myocardial MARK4 expression in patients with impaired cardiac contractility, resulting in an inverse correlation with the left ventricular ejection fraction. Myocardial MARK4 expression also correlated with echocardiographic E/e’, a central parameter of diastolic dysfunction. Mechanistically, our analyses revealed that MARK4 expression increases in SDB and under hypoxic conditions, as evidenced by significant correlations between myocardial MARK4 expression and factors like mean oxygen saturation, time with oxygen saturation below 90%, and the oxygen desaturation index. Multivariable regression analysis revealed that both left ventricular ejection fraction and mean oxygen saturation were independently associated with dysregulated MARK4 levels, even when controlling for important clinical covariables as potential confounders. Taken together, our findings demonstrate that MARK4 expression is highly increased in the myocardium of cardiovascular high-risk patients, suggesting it is a potential molecular target against cardiovascular diseases. Full article
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15 pages, 498 KiB  
Review
Sleep-Disordered Breathing and Central Respiratory Control in Children: A Comprehensive Review
by Marco Zaffanello, Angelo Pietrobelli, Luana Nosetti, Giuliana Ferrante, Erika Rigotti, Stefania Ganzarolli and Giorgio Piacentini
Children 2025, 12(3), 279; https://doi.org/10.3390/children12030279 - 25 Feb 2025
Viewed by 1197
Abstract
Background/Objectives: Sleep-disordered breathing (SDB) is a primary concern in children’s health. Research suggests that repeated oxygen drops during sleep—common in SDB—may harm the brainstem’s breathing control centres. This damage likely occurs through oxidative stress, inflammation, and cell death, which weaken the brain’s [...] Read more.
Background/Objectives: Sleep-disordered breathing (SDB) is a primary concern in children’s health. Research suggests that repeated oxygen drops during sleep—common in SDB—may harm the brainstem’s breathing control centres. This damage likely occurs through oxidative stress, inflammation, and cell death, which weaken the brain’s ability to regulate breathing. Over time, these effects could lead to functional changes (e.g., disrupted chemical signalling) and physical damage in critical brain regions, creating a cycle of unstable breathing. However, much of this evidence comes from animal or lab studies, leaving gaps in our understanding of how these mechanisms work in humans. This review synthesises existing research on how breathing disruptions during sleep—particularly episodes of intermittent hypoxia—affect the brain’s ability to control respiration in children and adolescents. Methods: We analysed studies from medical databases PubMed, Scopus, and Web of Science, focusing on how SDB (obstructive or central sleep apnoea) impacts the brain’s respiratory centres in young populations. Animal studies and research involving children on mechanical ventilation were excluded to focus on natural sleep patterns. Results: After removing duplicates, 54 studies remained. Additionally, 43 record were excluded for various reasons. Ultimately, 11 articles were selected for the final analysis, including three that focused on genetic conditions, such as Down syndrome, Prader–Willi syndrome, and Pierre Robin sequence. The findings suggest that repeated oxygen dips during sleep may harm the brainstem’s respiratory control areas, especially during critical developmental stages. This damage could lead to long-term issues, such as unstable breathing, cardiovascular strain, or neurological problems. However, most studies only captured the immediate effects of low oxygen, leaving uncertainty about permanent harm due to a lack of long-term follow-up. Conclusions: Repeated oxygen deprivation during sleep appears to damage the brainstem and disrupt breathing regulation. However, small study sizes and short observation periods limit the strength of these conclusions. Future research should use advanced imaging tools to clarify long-term risks, develop effective treatments, and track children over extended periods. More significantly, longer-term studies are urgently needed to guide clinical care for vulnerable populations. Full article
(This article belongs to the Section Pediatric Pulmonary and Sleep Medicine)
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10 pages, 1578 KiB  
Article
Examination of Respiratory Disturbance Index Before and After Cheiloplasty and Palatoplasty
by Ryo Murasugi, Hitoshi Kawanabe, Ayano Murakami, Yasuhiko Fukuya, Hideto Imura, Nagato Natsume, Ken Sato, Seiko Mitachi and Kazunori Fukui
Diseases 2025, 13(3), 64; https://doi.org/10.3390/diseases13030064 - 21 Feb 2025
Viewed by 578
Abstract
Background/Objectives: Pediatric sleep-disordered breathing (SDB) can cause behavioral and cognitive problems and even physical growth impairment, but it is often under-recognized. Cleft lip and/or palate (CLP) is a common birth defect and known risk factor for SDB. In this study, we examined the [...] Read more.
Background/Objectives: Pediatric sleep-disordered breathing (SDB) can cause behavioral and cognitive problems and even physical growth impairment, but it is often under-recognized. Cleft lip and/or palate (CLP) is a common birth defect and known risk factor for SDB. In this study, we examined the sleep breathing status in infants with unilateral CLP (UCLP) before and after cheiloplasty and palatoplasty. Methods: This prospective before–after study included infants with UCLP who could undergo the sleep breathing test and sleep for >1 h. Their sleep breathing status was assessed using a fiber-based sleep apnea sensor (Fiber-Based Sleep Apnea Syndrome Sensor®) on the day before surgery and 1–3 d after surgery. We calculated and compared the pre- and postoperative respiratory disturbance index (RDI) following the criteria proposed by the American Academy of Sleep Medicine. Results: The mean RDI significantly improved both after cheiloplasty (from 7.5 ± 4.6 to 2.7 ± 1.4 events/h, p = 0.007) and after palatoplasty (from 4.4 ± 2.3 to 1.7 ± 0.4 events/h, p = 0.010). Conclusions: Cheiloplasty and palatoplasty could improve SDB and reduce its adverse effects on the physical growth and development of infants with UCLP. Full article
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18 pages, 2376 KiB  
Article
Myocardial DYRK1B Expression Is Increased in Patients with Impaired Cardiac Contractility and Sleep-Disordered Breathing
by Fatma Bayram, Philipp Hegner, Anna-Maria Lauerer, Sönke Schildt, Dominik Wermers, Maria Johanna Baier, Julian Mustroph, Maria Tafelmeier, Zdenek Provaznik, Christof Schmid, Lars Siegfried Maier, Stefan Wagner, Michael Arzt and Simon Lebek
Antioxidants 2025, 14(2), 163; https://doi.org/10.3390/antiox14020163 - 29 Jan 2025
Viewed by 1380
Abstract
Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial [...] Read more.
Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial DYRK1B expression in patients with cardiovascular disease in the context of other comorbidities. In our study, we examined DYRK1B mRNA expression in human right atrial appendage biopsies from 159 patients undergoing elective coronary artery bypass surgery. Each patient was tested for sleep-disordered breathing the night prior to surgery. In this large representative study cohort with cardiovascular high-risk patients, we found that an impaired cardiac function as well as sleep-disordered breathing (SDB), including various oxidative stress parameters, were associated with an increased myocardial DYRK1B expression. A multivariate regression analysis revealed left ventricular ejection fraction and the presence of SDB as significant predictors of the myocardial DYRK1B expression independent of other clinical covariates. Based on these findings, DYRK1B represents a promising molecular target in patients with heart failure and reduced ejection fraction as well in patients with sleep-disordered breathing. Full article
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Article
Sleep Breathing Disorders’ Screening Among Children Approaching Orthodontic Evaluation: A Preliminary Study
by Marco Storari, Francesca Stramandinoli, Maurizio Ledda, Alberto Verlato, Alessio Verdecchia and Enrico Spinas
Appl. Sci. 2025, 15(1), 101; https://doi.org/10.3390/app15010101 - 26 Dec 2024
Viewed by 1285
Abstract
Background: The orthodontist can play an important role in the early detection of sleep-disordered breathing (SDB), aiding in the prevention of dentoskeletal complications and systemic issues. Early intervention supports proper pediatric development, emphasizing the need for SDB screening in orthodontics. SDB involves abnormal [...] Read more.
Background: The orthodontist can play an important role in the early detection of sleep-disordered breathing (SDB), aiding in the prevention of dentoskeletal complications and systemic issues. Early intervention supports proper pediatric development, emphasizing the need for SDB screening in orthodontics. SDB involves abnormal breathing during sleep, with obstructive sleep apnea (OSA) in children presenting unique diagnostic challenges compared to adults. Aim: This study aimed to identify children at risk for SDB through a validated screening questionnaire during orthodontic evaluations. Methods: This prospective study recruited children under 12 years of age between July 2023 and July 2024. The Sleep Clinical Record was used to screen for SDB indicators. Results: Among the 48 participants (31 females, 17 males) aged 5–12 years, 69% were identified as being at risk for SDB. Risk factors included oral breathing, nasal obstruction, tonsillar hypertrophy, malocclusion, high Friedman scores, narrow palates, and positive Brouillette phenotypes, all showing significant correlations (p < 0.05). Conclusion: The findings underline the critical importance of early SDB screening in orthodontic settings. These preliminary results encourage further research on larger cohorts to refine diagnostic tools and interventions. Early recognition and management of SDB can significantly enhance systemic health and craniofacial outcomes in pediatric patients. Full article
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