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

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

Deadline for manuscript submissions: 25 February 2026 | Viewed by 6943

Special Issue Editors

Dr. Ivana Pavlinac Dodig

E-Mail Website
Guest Editor
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

E-Mail Website
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

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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 (3 papers)

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24 pages, 3207 KB  
Article
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
Viewed by 907
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 [...] Read more.
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  
Article
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
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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 [...] Read more.
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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Other

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38 pages, 2786 KB  
Systematic 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 2 | Viewed by 2572
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 [...] Read more.
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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