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Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 29 September 2026 | Viewed by 15793

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Editors

Dr. Ivana Pavlinac Dodig

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Department of Neuroscience, University of Split School of Medicine, Sleep Medicine Center, 21000 Split, Croatia
Interests: obstructive sleep apnea (OSA); sleep disorders; sleep-disordered breathing; oxidative stress in sleep apnea, inflammation and sleep apnea; cardiovascular comorbidities of OSA; biomarkers for sleep apnea; therapeutic targets for OSA; translational research in sleep medicine; neurocognitive impairment related to sleep disorders

Dr. Renata Pecotic

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Guest Editor

Department of Neuroscience, University of Split School of Medicine, Sleep Medicine Center, 21000 Split, Croatia
Interests: obstructive sleep apnea; anesthetics; sleep medicine; phrenic nerve recording; long-term facilitation

Special Issue Information

Dear Colleagues,

Obstructive sleep apnea (OSA) is a prevalent, yet underdiagnosed, sleep-related breathing disorder characterized by intermittent upper airway obstruction and fragmented sleep. It involves complex and multifactorial pathophysiological mechanisms that contribute to diverse clinical phenotypes and a wide range of systemic effects. Recent research has enhanced our understanding of OSA’s heterogeneity, including its pathophysiological mechanisms that lead to strong associations with cardiovascular, metabolic, and neurocognitive comorbidities, as well as its impact on daytime functioning and overall quality of life.

Despite these advances, important challenges remain. A deeper understanding of the underlying mechanisms of and the interactions between OSA and its comorbid conditions is still needed. At the same time, effective management continues to be hindered by the limitations of current therapies, most notably, suboptimal adherence to continuous positive airway pressure (CPAP), the gold-standard treatment. These challenges underscore the importance of improved disease phenotyping, the identification of reliable biomarkers, and the exploration of novel therapeutic targets, as well as efforts to optimize both established and emerging treatment strategies.

This Special Issue aims to provide a comprehensive overview of current research on OSA, focusing on disease mechanisms, comorbidities, and the optimization of emerging and established therapies. We welcome manuscripts addressing molecular and physiological mechanisms, novel diagnostic or prognostic biomarkers, translational studies, and personalized treatment approaches, including innovations to improve therapy adherence.

By integrating multidisciplinary perspectives, this Special Issue seeks to advance clinically relevant research and support the development of more effective, individualized management pathways for patients living with OSA.

Dr. Ivana Pavlinac Dodig
Dr. Renata Pecotic
Guest Editors

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Keywords

obstructive sleep apnea
sleep-disordered breathing
pathophysiology
cardiometabolic comorbidities
precision medicine
CPAP
sleep diagnostics
biomarkers
neurocognitive impairment
new therapies

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Published Papers (10 papers)

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Research

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12 pages, 606 KB

Open AccessArticle

Phenotyping of Obstructive Sleep Apnea Syndrome and Association with Cognitive Impairment, a Real-Life Study

by Filippo Capilupi, Valentino Condoleo, Giandomenico Severini, Giuseppe Armentaro, Corrado Pelaia, Ilaria Gareri, Pasquale Loiacono, Maria Rosangela Scarcelli, Francesco Maruca, Alberto Panza, Marilisa Panza, Sofia Miceli, Raffaele Maio and Angela Sciacqua

Biomedicines 2026, 14(6), 1187; https://doi.org/10.3390/biomedicines14061187 - 24 May 2026

Viewed by 537

Abstract

Introduction: Obstructive sleep apnea (OSA) is highly prevalent, affecting up to 50% of individuals over 65 years. Elderly patients often present with atypical, fewer and less severe symptoms, suggesting age-specific phenotypes. However, comprehensive clinical phenotyping that incorporates cognitive outcomes remains limited. This study aimed to characterize OSA phenotypes through cluster analysis and evaluate their association with cognitive impairment, independently of age. Materials and Methods: Between 2020 and 2024, 409 adults with moderate-to-severe OSA were enrolled and stratified into three age groups (<65, 65–74, ≥75 years). All underwent home sleep apnea testing (HSAT), comprehensive symptom assessment, Epworth Sleepiness Scale (ESS), and Montreal Cognitive Assessment (MoCA, pathological ≤ 25 pts). Hierarchical cluster analysis (Ward’s method) used AHI, T90, BMI, and ESS. Logistic regression identified independent predictors of cognitive impairment. Results: Older groups showed lower BMI, higher comorbidity burden, fewer symptoms, and greater cognitive impairment prevalence (4.5% vs. 9.7% vs. 45.9%; p < 0.001), despite comparable polysomnographic severity across age groups. Cluster analysis identified three phenotypes: Cluster 1 (classical OSA: high AHI, BMI, T90, ESS); Cluster 2 (geriatric phenotype: low AHI, BMI, T90, ESS, highest cognitive impairment rate: 27.7%); Cluster 3 (hypersymptomatic: low AHI and T90, high sleepiness and asthenia, prevalent depression). On multivariate regression, age (OR 1.155; p < 0.001), male sex (OR 2.223; p = 0.034), and Cluster 2 (OR 3.131; p < 0.001) were independent predictors of cognitive impairment. Conclusions: Three clinically distinct OSA phenotypes were identified regardless of age and severity. The geriatric phenotype was associated with three-fold increased risk of cognitive impairment, supporting routine cognitive screening and age-adapted diagnostic strategies in elderly OSA patients. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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11 pages, 1205 KB

Open AccessArticle

Associations Between Anemia and Obstructive Sleep Apnea in Patients with Cystic and Non-Cystic Bronchiectasis: A Prospective Cross-Sectional Study

by Baran Balcan, Duygu Vezir, Ramazan Ocal, Caner Cinar, Erdal Aksoy, Yeliz Celik and Berrin Ceyhan

Biomedicines 2026, 14(4), 915; https://doi.org/10.3390/biomedicines14040915 - 17 Apr 2026

Viewed by 650

Abstract

Background: Anemia and obstructive sleep apnea (OSA) are prevalent comorbidities in bronchiectasis and may share overlapping pathophysiological mechanisms. However, their combined impact on clinical outcomes in bronchiectasis remains underexplored. We aimed to investigate the associations between anemia, OSA, and clinical characteristics in patients with bronchiectasis, including cystic fibrosis (CF) and non-CF subtypes. Methods: 70 adults with bronchiectasis (35 CF-related, 35 non-CF) underwent polysomnography. Anemia was defined using standard hemoglobin < 13 g/dL for men and <12 g/dL for women. Clinical, nutritional, and sleep-related variables were assessed, and associations with anemia were evaluated. Results: Anemia was present in 24.3% of participants. Compared to non-anemic patients, those with anemia had significantly higher rates of female sex (38.5% vs. 6.5%, p = 0.002), nutritional problems (47.1% vs. 20.8%, p = 0.034), OSA prevalence (94.1% vs. 54.7%, p = 0.003), and annual hospitalizations (1.41 ± 0.41 vs. 0.43 ± 0.10, p = 0.002). In multivariate analysis, female sex (OR: 12.32; 95% CI: 3.12–45.96; p = 0.002) and OSA (OR: 4.70; 95% CI: 2.67–45.29; p = 0.007) remained independent predictors of anemia. Subgroup analysis showed a significant univariate association between OSA and anemia in CF patients (p = 0.045), while hospitalization frequency was an independent predictor of anemia in non-CF bronchiectasis (p = 0.040). Conclusions: Anemia in bronchiectasis is independently associated with female sex and OSA, with additional exploratory subgroup findings. These findings indicate an association between OSA and anemia within bronchiectasis populations; however, the cross-sectional design precludes conclusions regarding directionality or causality. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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14 pages, 3232 KB

Open AccessArticle

Shape Matters: Computational Fluid Dynamics Analysis of Epiglottis Shape Influence on Airway Collapse in Obstructive Sleep Apnea Patients

by Timi Gomboc, Matjaž Hriberšek and Matej Delakorda

Biomedicines 2026, 14(3), 553; https://doi.org/10.3390/biomedicines14030553 - 28 Feb 2026

Viewed by 577

Abstract

Background: The study investigates the influence of epiglottis morphology on airflow dynamics and mechanical loading using computational fluid dynamics (CFD) in patients with obstructive sleep apnea (OSA), where the epiglottis may contribute to upper airway obstructions during sleep. Methods: A two-stage analysis was conducted: first, using a simplified airway model with two distinct epiglottis shapes (flat and curved), and second, using patient-specific 3D airway geometries derived from computed tomography (CT) scans. The simplified model enabled isolated analysis of flow-related aerodynamic forces and torques acting on the epiglottis across varying flow rates and inclination angles. Results: Results showed that the flat-shaped epiglottis was subjected to higher aerodynamic loads, particularly at lower flow rates, indicating increased susceptibility to collapse. These findings were corroborated by simulations on patient-specific 3D airway models. Conclusions: The study confirms that epiglottis morphology plays a critical role in the pathogenesis of OSA and underscores the potential of CFD for personalized assessment and treatment planning. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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15 pages, 516 KB

Open AccessArticle

Obstructive Sleep Apnea in Psoriatic Arthritis: Clinical Characteristics and Comorbidities

by Miguel A. Hernández-Mezquita, Esther Toledano, Rubén Queiró, Javier Martín-Vallejo, María José Fernández-Gómez, Carolina Cristina Chacón, Roberto Díaz-Peña, Pilar Sánchez-Conde, Daniel Martín, Cristina Hidalgo, María Dolores Sánchez, Inés Llamas-Ramos, Erik Díaz and Carlos Montilla

Biomedicines 2026, 14(3), 491; https://doi.org/10.3390/biomedicines14030491 - 24 Feb 2026

Cited by 1 | Viewed by 1200

Abstract

Background: Obstructive sleep apnea (OSA) is increasingly recognized in chronic inflammatory diseases, yet its prevalence and clinical correlates in psoriatic arthritis (PsA) remain poorly characterized. Objective: The objective of this study was to evaluate OSA prevalence and its relationship with disease activity, functional impairment, and comorbidities in PsA patients. Methods: A cross-sectional analysis of 247 consecutive PsA patients was conducted. OSA diagnosis was determined through medical record review. Disease activity was assessed using cDAPSA and ASDAS-CRP. Functional disability was measured using HAQ-DI and BASFI. Sleep quality (PSQI) and psychological symptoms (HADS) were evaluated. Inflammatory markers included CRP, IL-6, and TNF-α. Multivariable logistic regression identified independent predictors of OSA. Results: OSA prevalence was found to be 8.9% (22/247). OSA+ patients had significantly higher median age (58.0 vs. 54.0 years, p = 0.02), tender joint count (2.0 vs. 1.0, p = 0.002), functional disability (1.1 vs. 0.3, p = 0.001), fatigue (30.5 vs. 38.0, p = 0.04), anxiety (7.5 vs. 5.0, p = 0.03), depression (7.0 vs. 3.0, p = 0.004), and worse sleep quality (11.5 vs. 7.0, p = 0.001). Notably, no significant differences in inflammatory markers (CRP, swollen joints) were found between groups despite substantially higher pain burden in OSA+ patients. Female sex and greater tender joint count emerged as independent predictors of OSA. Conclusions: OSA occurs in ~9% of unselected PsA patients and is independently associated with functional disability, psychological distress, and elevated tender joint counts despite comparable inflammatory markers. This dissociation suggests that OSA drives pain amplification through non-inflammatory mechanisms. These findings support the use of systematic OSA screening in PsA patients with pain or disability disproportionate to inflammatory burden, particularly in those with psychological comorbidities. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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9 pages, 222 KB

Open AccessArticle

Tongue Pressure as a Predictor of Tongue Base Collapse in Patients with Obstructive Sleep Apnea Syndrome

by Ying-Chieh Hsu, Meng-Xun Goh, Tung-Tsun Huang and Hsueh-Yu Li

Biomedicines 2026, 14(2), 465; https://doi.org/10.3390/biomedicines14020465 - 19 Feb 2026

Viewed by 1348

Abstract

Background: This study investigated the association between tongue strength, measured using the Iowa Oral Performance Instrument (IOPI), and upper airway collapse patterns observed during drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea syndrome (OSAS). Methods: Thirty patients who underwent polysomnography, DISE, and tongue pressure measurement were retrospectively analyzed. Upper airway collapse was assessed using the VOTE classification. The tongue strength task performed using the IOPI requires participants to compress an air-filled bulb placed on the hard palate with anterior tongue to generate maximum isometric tongue pressure. Group comparisons and ordinal logistic regression with Firth’s penalized likelihood were performed to evaluate associations between tongue pressure and collapse patterns. Results: The participants had a mean age of 41.5 ± 12.5 years, including 27 males and 3 females. The mean tongue strength was 50.4 ± 15.3 kPa, with no significant sex-related differences. Patients with tongue strength <40 kPa showed significantly higher odds of tongue base collapse (adjusted OR 12.79, 95% CI 1.30–126.91) and epiglottic collapse (adjusted OR 54.05, 95% CI 1.66–1760.25). No significant differences were observed for velum or oropharyngeal collapse. Conclusions: Lower tongue strength was associated with increased likelihood of tongue base collapse during DISE. Tongue strength measurement may serve as a practical, non-invasive tool for identifying patients with reduced tongue muscle function and potential tongue-related airway obstruction. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

24 pages, 3207 KB

Open AccessArticle

Reevaluating C-Reactive Protein for Perioperative Risk Stratification: The Overlooked Role of Sleep Apnea in Cardiac Surgery Outcomes

by Andrei Raul Manzur, Caius Glad Streian, Ana Lascu, Maria Alina Lupu, Horea Bogdan Feier and Stefan Mihaicuta

Biomedicines 2025, 13(10), 2546; https://doi.org/10.3390/biomedicines13102546 - 18 Oct 2025

Cited by 1 | Viewed by 1611

Abstract

Background/Objectives: C-reactive protein (CRP) is widely used as a marker of perioperative inflammation, but its predictive value for cardiac surgical outcomes remains uncertain. Obstructive sleep apnea (OSA), a prevalent and underrecognized comorbidity, may independently contribute to postoperative complications through non-inflammatory mechanisms. This study aimed to reevaluate the prognostic role of CRP and determine the clinical impact of OSA severity on postoperative recovery, focusing on new-onset atrial fibrillation (AF), prolonged intubation time, and postoperative CPAP/AIRVO use as indicators of respiratory burden. Methods: In this prospective cohort of 142 elective cardiac surgery patients, preoperative polysomnography and serial CRP measurements were obtained. Multivariable regression, mediation analysis, and propensity score matching (PSM) were performed to evaluate associations between OSA severity, CRP, and perioperative outcomes (AF, intubation time, CPAP/AIRVO use). Results: OSA severity independently predicted prolonged intubation (β = 1.74, p = 0.0019) and new-onset AF (β = 0.85, p = 0.004), even after excluding patients with preexisting arrhythmia. CRP showed poor discriminatory power as a standalone biomarker (AUC for IOT > 14 h = 0.445) and did not mediate OSA–outcome associations. However, CRP > 2.1 mg/dL doubled the odds of moderate-to-severe OSA (OR = 2.05, p = 0.041). A composite score integrating AHI, BMI, and postoperative CRP strongly correlated with postoperative respiratory support (p < 0.0001). Conclusions: OSA exerts a stronger and more consistent influence on perioperative outcomes than CRP, challenging reliance on CRP for risk stratification. Incorporating objective OSA screening and spirometry into preoperative assessment may enhance perioperative risk prediction and guide personalized management strategies. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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11 pages, 1276 KB

Open AccessArticle

Efficacy of a Novel Treatment Approach for Obstructive Sleep Apnea

by Brandon Hedgecock, Max Kerr, Jenny Tran, Ben Sutter, Phillip Neal, Gilles Besnainou, Erin Mosca and Len Liptak

Biomedicines 2025, 13(10), 2413; https://doi.org/10.3390/biomedicines13102413 - 2 Oct 2025

Cited by 1 | Viewed by 3788

Abstract

Objective: This study evaluates the efficacy of a novel approach to oral appliance therapy (“OAT”) for the treatment of obstructive sleep apnea (“OSA”). This novel approach utilizes a systemized, oximetry-informed, treatment protocol and a precision-custom oral appliance. Methods: Sixty consecutive patients diagnosed with OSA were treated at Sleep Better Austin (“SBA”) using a structured, multi-step protocol and a precision-custom oral appliance (ProSomnus EVO). Baseline and post-treatment apnea–hypopnea index (“AHI”) values were compared using a matched-pair design. The primary outcome was the percentage of patients achieving a residual AHI of <10 events/h. Secondary outcomes included severity classification improvement. Results: In total, 90% of patients achieved the primary endpoint, and 87% improved by at least one severity classification. The mean AHI improved by 63% from baseline with the precision-custom OAT in situ (p < 0.001). In the moderate-to-severe subgroup, AHI improved by 70%, with 100% of severe patients achieving a residual AHI of <20 and a ≥50% improvement, without patient preselection. No serious adverse events were reported, and all patients continued therapy at follow-up. Conclusions: Precision-custom OAT, when delivered through a standardized clinical protocol informed by oximetry, can be a highly effective and well-tolerated treatment for OSA. These findings support its broader adoption as a non-invasive alternative to continuous positive airway pressure (“CPAP”) and surgical interventions, particularly for patients seeking personalized, high-compliance solutions. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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Review

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21 pages, 2342 KB

Open AccessReview

Obstructive Sleep Apnea and Cardiovascular Disease: Mechanisms, Diagnostics, and Emerging Therapeutic Approaches

by Bridget R. Alber, Emily C. Cheung, Rebekah Russo, Vivek Jain, Kathryn Jaques Schunke, David Mendelowitz and Matthew W. Kay

Biomedicines 2026, 14(6), 1263; https://doi.org/10.3390/biomedicines14061263 - 1 Jun 2026

Viewed by 645

Abstract

Current diagnostic methods for OSA and CSA are costly, unreliable, and the therapeutic options are limited, with varying efficacy across patients. As the prevalence of sleep apnea and cardiovascular disease continue to rise, identifying innovative therapies through advances in biomedicine and personalized medicine has become increasingly critical. This review discusses the mechanistic links between sleep apnea and subsequent cardiovascular outcomes from a technical perspective, focusing on innovations currently applied to the diagnosis and treatment of sleep apnea, and opportunities for further advancement in the field. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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Other

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13 pages, 1075 KB

Open AccessSystematic Review

Hypoglossal Nerve Stimulation Therapy for Pediatric Obstructive Sleep Apnea: A Meta-Analysis

by Ji Ho Choi, Soo Kyoung Park, Jae Hoon Cho, Ji Eun Moon and Seok Hyun Cho

Biomedicines 2026, 14(4), 770; https://doi.org/10.3390/biomedicines14040770 - 28 Mar 2026

Viewed by 643

Abstract

Background/Objectives: This study evaluates the efficacy of hypoglossal nerve stimulation as an alternative intervention for pediatric patients with obstructive sleep apnea (OSA) unresponsive to standard therapies and examines the uniformity of therapeutic outcomes across different patient cohorts. Methods: An extensive systematic search was performed across four principal databases (PubMed, EMBASE, Cochrane Library, and Web of Science) utilizing keywords associated with pediatric OSA and hypoglossal nerve stimulation, encompassing studies up to July 2025 that provided objective polysomnographic metrics (e.g., apnea-hypopnea index [AHI] values) to enable the quantitative assessment of pre- and post-intervention effects in children. The primary outcome measured was the ratio of means (ROM), determined from pre–post data in single-group studies, with summary estimates obtained using the fixed-effects model. Results: The systematic review included nine eligible studies with a total of 140 pediatric subjects, the majority of whom were adolescents with Down syndrome. AHI meta-analysis outcomes indicated a marked improvement in OSA severity, yielding an overall ROM of 0.57 [95% confidence interval: 0.49–0.65]. The therapeutic benefit demonstrated a high degree of uniformity across cohorts, as indicated by minimal statistical heterogeneity (I² = 16%, p = 0.30). Funnel plot assessment showed no statistically significant evidence of systematic publication bias. Conclusions: Current evidence suggests that hypoglossal nerve stimulation therapy is a safe, effective, and valuable alternative for pediatric OSA patients who do not respond to conventional therapies. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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38 pages, 2786 KB

Open AccessSystematic Review

Obstructive Sleep Apnea and Outcomes in Cardiac Surgery: A Systematic Review with Meta-Analytic Synthesis (PROSPERO CRD420251049574)

by Andrei Raul Manzur, Alina Gabriela Negru, Andreea-Roxana Florescu, Ana Lascu, Iulia Raluca Munteanu, Ramona Cristina Novaconi, Nicoleta Sorina Bertici, Alina Mirela Popa and Stefan Mihaicuta

Biomedicines 2025, 13(7), 1579; https://doi.org/10.3390/biomedicines13071579 - 27 Jun 2025

Cited by 3 | Viewed by 3529

Abstract

Background: Obstructive sleep apnea (OSA) is a prevalent but frequently underdiagnosed comorbidity in patients undergoing cardiac surgery, including coronary artery bypass grafting (CABG), aortic valve replacement (AVR), and mitral valve repair or replacement (MVR). This systematic review and meta-analytic synthesis investigates the relationship between OSA and postoperative morbidity and mortality, with particular attention to the predictive utility of established screening instruments. Methods: A systematic search of the PubMed database was conducted (April 2025), identifying 724 articles published in the last ten years. Seventeen primary studies met the inclusion criteria for qualitative synthesis, and four additional studies were included in the meta-analyses. Outcomes assessed included atrial fibrillation, major adverse cardiac and cerebrovascular events (MACCE), acute kidney injury (AKI), respiratory complications, pneumonia, hospital length of stay (LOS), and mortality. Risk of bias was assessed qualitatively based on study design and reporting limitations. This review was registered in the PROSPERO database under registration number CRD420251049574. Results: Meta-analyses demonstrated significantly elevated odds of atrial fibrillation (OR = 2.44, 95% CI: 1.46–4.07), major adverse cardiac and cerebrovascular events (OR = 2.06, 95% CI: 1.61–2.63), acute kidney injury (OR = 2.24, 95% CI: 1.67–3.01), and respiratory complications (OR = 1.15, 95% CI: 1.05–1.25) among patients with OSA. Additionally, OSA was associated with a significantly prolonged hospital length of stay (standardized mean difference [SMD] = 0.62, 95% CI: 0.46–0.78) and a marginal increase in pneumonia risk (OR = 1.07, 95% CI: 1.00–1.15). Evidence regarding stroke, intensive care unit (ICU) stay, and mortality was inconsistent or underpowered. Conclusions: Across core outcomes, findings were consistent across multiple studies involving a large patient population. Obstructive sleep apnea is a clinically consequential risk factor in cardiac surgery, associated with increased perioperative complications and prolonged hospitalization. These findings support the integration of routine OSA screening into preoperative risk assessment protocols. Further prospective, multicenter trials are warranted to assess the efficacy of perioperative management strategies, including continuous positive airway pressure (CPAP) therapy, in improving surgical outcomes. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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