Open research questions in Obstructive Sleep Apnea Research

What the literature leaves open

• Background: Paediatric obstructive sleep apnea (OSA) is a prevalent yet under-recognised condition associated with significant neurocognitive, behavioural, and cardiovascular morbidity.

  Screening for sleep related breathing disorders and assessing the risk of obstructive sleep apnea in 2-18 years of children using paediatric sleep questionnaire: an observational study · 2026 · DOI

• Because symptoms and comorbidities that commonly coexist with OSA may influence both headache susceptibility and perceived sleep quality, the respective contributions of respiratory abnormalities and sleep disruption to MHs remain uncertain, particularly in women.

  Morning Headaches as a Specific Obstructive Sleep Apnea Characteristic in a Large Sleep Clinic Population · 2026 · DOI

• Increasing attention has been directed toward comorbidities that may aggravate disease burden, including sleep-disordered breathing (SDB), which remains underrecognized in this population.

  Neurocognitive and neurophysiological consequences of sleep-disordered breathing in bronchiectasis: the role of respiratory rehabilitation · 2026 · DOI

• Pediatric Use: The safety and effectiveness of Zepbound have not been established in pediatric patients. Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Available data with tirzepatide in pregnant patients are insufficient to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking Zepbound, including whether modifying preoperative fasting recommendations or temporarily discontinuing Zepbound could reduce the incidence of retained gastric contents.

  Tirzepatide: sleep apnea's biggest nightmare · 2026 · DOI

• Abstract Background The relationship between obstructive sleep apnea syndrome (OSAS) and pulmonary embolism (PE) remains inadequately characterized, and prospective data obtained with objective sleep testing in confirmed PE patients are scarce.

  Prevalence of obstructive sleep apnea syndrome in patients with pulmonary embolism: a prospective observational study · 2026 · DOI

• Introduction: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), but clinical correlates of polysomnography-derived severity remain incompletely defined.

  Understanding Severe Sleep-Disordered Breathing in Down Syndrome: Insights from a Clinical–Polysomnographic Cohort · 2026 · DOI

• Finally, the behavioral impacts of solriamfetol on patients remain unexplored, specifically its potential effects on occupational injury and motor vehicle crash risk in OSA-EDS cohorts. Further validation is warranted in larger cohorts and across diverse ethnic populations in real-world settings.

  Post Hoc Analysis of Solriamfetol Efficacy in Obstructive Sleep Apnea Patients with Excessive Daytime Sleepiness Stratified by Disease Severity · 2026 · DOI

• Abstract INTRODUCTION Obstructive sleep apnea (OSA) is a potential risk factor for cognitive impairment and dementia; however, its contribution in midlife and interactions with APOE ε4 remain unclear.

  Associations of self‐reported obstructive sleep apnea with cognition and dementia risk in cognitively unimpaired middle‐aged adults · 2026 · DOI

• underwent should be in a sleep initial recordings simultaneous PSG The strength of both studies lies in its evaluation of the diagnostic accuracy and real-world feasibility of PG for detecting moderate-to-severe OSA, and evaluating unobtrusively AF recurrence and burden in patients with AF. By integrating a validation and feasibility study across two centers, our design reflects routine clinical practice, including inter-scorer variability Additionally, patient-reported interpretation. in questionnaires were used evaluate user-friendliness. to Importantly, patients had the option to consult a sleep clinic following a positive screening result, and most of them did, highlighting the acceptability and clinical relevance of this approach. acknowledged. Participants in the first study were recruited from patients with AF already referred in-hospital PSG, representing a likely high pretest probability of OSA. population with a Additionally, the measurement order was not randomized, as all patients and NOX-T3s examination, followed by a consecutive night of NOX-T3s evaluation. This may have introduced a habituation effect after the first night of testing, as patients are known to sleep worse during laboratory and may influenced PG comfort scores. Furthermore, the relatively small sample sizes in both studies limit the generalizability of the findings. The optimal NOX-T3s AHI cut-off value of 11.1 identified for home-based OSA screening was derived from a relatively small cohort and should ideally be confirmed in a larger, independent external population before it can be broadly implemented in clinical practice. In addition, the NOXFib-AF inclusion criteria to own a smartphone and willingness to in a digital monitoring program may have participate introduced selection bias, less digitally experienced or engaged patients. Moreover, the impact of OSA diagnosis on subsequent patient management and AFrelated outcomes was not assessed within the present study. As such, we were unable to evaluate downstream clinical endpoints, including CPAP compliance, changes in AF management, or the effect of OSA treatment on AF burden and symptoms. This represents an important limitation, as the ultimate value of opportunistic screening depends on its ability to translate into improved patient effective outcomes. This will occur in the ongoing STAROSA study (NCT06263608), a prospective pre-post implementation study designed to evaluate the impact of a structured testing and treatment program for OSA using the NOX-T3s device and a Fitbit smartwatch with the FibriCheck algorithm on the AF (symptom) burden in an AF population.

  Validation and implementation of ambulatory obstructive sleep apnea polygraphy screening combined with wearable semi-continuous heart rhythm monitoring in patients with atrial fibrillation: a validation and a pilot study · 2026 · DOI

• Structured interdisciplinary care pathway for OSA detection in AF patients The findings of this study, including key implementation aspects such as feasibility, data quality, data analysis and translation, patient adherence, acceptability, and patients’ willingness to participate in such a digital health care program, were instrumental in the design of the ongoing prospective prepost implementation STAROSA study (NCT06263608). In this study, we aim to evaluate the effect of systematic OSA screening and treatment pathway on AF burden, defined as the proportion of patients with AF, AF recurrence rate, and time spent in AF over the monitoring period. Home-based screening will be in paroxysmal and performed using the NOX-T3s device persistent AF patients, applying the optimal cut-off value of 11.1 (determined in the NOX-T3s validation study) to identify patients with clinically relevant OSA. Patients with a positive screening result will undergo confirmatory in-hospital PSG. The waiting period for PSG will serve as a baseline rhythmmonitoring phase of three months, during which AF burden will be assessed using the FibriCheck application for twice-a-day semi-continuous spot-check monitoring interval measurements. Following PSG-confirmed OSA diagnosis, patients will initiate CPAP therapy, after which a second threemonth monitoring phase will be conducted to evaluate changes in AF burden after treatment initiation. smartwatch-based combined with recordings, 9-minute via If the STAROSA study demonstrates favorable outcomes, this approach may support the development of a structured interdisciplinary care pathway for OSA detection in AF patients, characterized by close collaboration between patients, the AF clinic, and the sleep clinic. In this model, screening would be initiated in the AF clinic and managed by specialized AF nurses in collaboration with cardiologists. Nurses would provide patients with one or more validated digital monitoring tools (e.g., NOX-T3s and smartwatch with FibriCheck), depending on clinical indication. Patients would use these devices at home and return them to the clinic for analysis by trained AF nurses or technologists. Patients with evidence suggestive of clinically relevant OSA would be referred for confirmatory PSG, which is required in Belgium for CPAP reimbursement. therapy, smartwatch-based monitoring would be continued to assess the impact of treatment on AF burden and sleep-related outcomes. Follow-up would be performed by a multidisciplinary team involving both AF and sleep clinics, enabling coordinated education, motivational including patient-centered interviewing, and support for self-management strategies such as CPAP adherence and weight management. This collaborative pathway allows bidirectional communication between clinics, facilitating timely management of both AF and OSA-related issues. Ultimately, this may reduce existing barriers to systematic OSA screening in AF populations. However, this proposed care pathway requires formal evaluation before implementation in routine clinical practice.

  Validation and implementation of ambulatory obstructive sleep apnea polygraphy screening combined with wearable semi-continuous heart rhythm monitoring in patients with atrial fibrillation: a validation and a pilot study · 2026 · DOI

• Additionally, although the selected literature represents high-impact and recent studies, the number of references is limited to a defined set, which may not capture the full scope of available research. Additionally, maxillofacial trauma emerges as a critical yet often underrecognized contributor to long-term airway dysfunction.

  Functional Airway Medicine: Integrating Otolaryngology, Dentofacial Structures, Trauma, and Sleep in a Multidisciplinary Clinical Model · 2026 · DOI

• Despite different scan protocols and measurement definitions, the retropalatal region was the predominant site of airway narrowing; however, this finding alone is insufficient for diagnosis or severity grading. As these variables were insufficiently controlled for in most included studies, the isolated interpretation of retropala- tal narrowing is clinically limited.

  Diagnostic and prognostic value of (cone-beam) computed tomography in dental sleep medicine for obstructive sleep apnea: a systematic review · 2026 · DOI

• Background and ObjectivesChildren with Down syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA) due to anatomic, neuromuscular, immunological and metabolic factors, yet the contribution of the tonsillar microbiome to airway obstruction in this population remains unexplored.

  Altered Tonsillar Microbiome in Children with Down Syndrome and Obstructive Sleep Apnea · 2026 · DOI

• However, the limitations, including the lack of data on specific headache disorders and reliance on HIT-6 as a composite headache metric, warrant further investigation, ideally based on randomized controlled trials, to clarify the specific anatomical traits influencing this outcome.

  Effect of complete airway repositioning and expansion on headache severity in patients with obstructive sleep apnea · 2026 · DOI

• Given the multifactorial nature of pediatric OSA, these results should be interpreted cautiously and warrant further investigation in larger longitudinal studies.

  Long-Term Changes Following Orthopedic Mandibular Advancement Therapy in Pediatric Obstructive Sleep Apnea: a 7-Year Follow-up Study · 2026 · DOI

• Statement. https://doi.org/10.1001/jama.2022.20304 JAMA Verbraecken J (2022) More than sleepiness: prevalence and relevance of nonclassical symptoms of obstructive sleep apnea. Curr Opin Pulm Med 28:552–558. https://doi.org/10.1097/MCP.0000000000000915 Verlato G, Melotti R, Olivieri M, et al (2010a) Asthmatics and ex-smokers respond early, heavy smokers respond late to mailed surveys in Italy. Respir Med 104:172–179. https://doi.org/10.1016/j.rmed.2009.09.022 Verlato G, Melotti R, Olivieri M, et al (2010b) Asthmatics and ex-smokers respond early, heavy smokers respond late to mailed surveys in Italy. Respir Med 104:172–179. https://doi.org/10.1016/j.rmed.2009.09.022 Yasin R, Muntham D, Chirakalwasan N (2016) Uncovering the sleep disorders among young doctors. Sleep Breath 20:1137–1144.

  Risk of obstructive sleep apnea among healthcare workers: a systematic review and meta-analysis · 2026 · DOI

• include maintaining a patients—defined as body mass index (BMI) ≥ consistent sleep-wake schedule (even on 30 kg/m²—regular aerobic exercise and a weekends), ensuring a dark, quiet, and cool structured, hypocaloric healthy diet should be sleeping environment, avoiding electronic systematically encouraged. Robust evidence screens for at least 60 minutes prior to bedtime, from randomized controlled trials and and establishing a relaxing pre-sleep longitudinal cohort studies demonstrates that ritual.[39][40][41][42] Additionally, weight loss (whether achieved through lifestyle positional therapy—encouraging sleep in the intervention, pharmacotherapy, or bariatric non-supine position—may be recommended surgery) produces clinically meaningful for patients with positional OSA (defined as a improvements across multiple domains: supine AHI at least twice that of non-supine reduction in the Apnea-Hypopnea Index (AHI) AHI). Simple interventions such as the use of a and Respiratory Disturbance Index (RDI), specialized positional pillow, a wearable amelioration of objective and subjective vibrating device, or even a tennis shirt sewn daytime sleepiness, improvement in metabolic into the back of a pajama top can effectively parameters (including insulin sensitivity and reduce supine sleep time. Critically, all patients lipid profiles), and enhanced blood pressure with OSA must be advised that alcohol and control.[37] The mechanistic basis for sedating medications (including Uva Clinical Research Lab 2026 © Uva Clinical Anaesthesia and Intensive Care ISSN 2827-7198 Obstructive Sleep Apnea: 18 May 2026 10 Uva Clinical Research Lab 2026 © Uva Clinical Anaesthesia and Intensive Care ISSN 2827-7198 Obstructive Sleep Apnea: 18 May 2026 benzodiazepines, non-benzodiazepine airway pressure (EPAP), is useful for patients hypnotics, and opiates) exacerbate OSA who require high pressures, experience CPAP severity by reducing pharyngeal muscle tone, intolerance, or have concomitant blunting arousal responses to airway occlusion, hypoventilation or obesity hypoventilation and prolonging the duration of obstructive syndrome. Auto-titrating positive airway events, thereby worsening oxyhemoglobin pressure (APAP) automatically adjusts the desaturation.

  Obstructive Sleep Apnea: A Comprehensive Clinical Review of Pathophysiology, Diagnosis, Multimodal Management, and Interprofessional Care · 2026 · DOI

• Despite the current study’s strength of recruiting a diverse population of individuals with non-military trauma expo- sure, it has some limitations. Firstly, as noted above, the finding of OSA prevalence being similar between groups may be due to inadequate statistical power. Seven of eight participants with OSA endorsed some level of PTSD symp- toms, including re-experiencing symptoms. Larger future studies will be required to investigate OSA prevalence fur- ther. Secondly, our sample represents a population at an already low risk of having OSA, being that they were pre- dominantly young and with low BMIs. Of note, prior stud- ies in individuals with non-military traumas have reported high rates of OSA in sexual assault survivors [7] or vic- tims of crime [6] with only slightly older age and higher BMI than our sample. While this supports the choice to investigate OSA prevalence in the young population, we are nonetheless limited in our ability to measure how risk factors such as age and weight might interact with the observed heightened VRA to predispose OSA in the PTSD population. Thirdly, we did not perform clinical diagnos- tic interviews to diagnose PTSD. However, we used strin- gent cutoffs for considering likely or subsyndromal PTSD with the requirement that they must have elevated PCL-5 scores in addition to endorsing re-experiencing symptoms (nightmares or intrusions). Finally, we have estimated the ventilatory response to arousal using nasal pressure as opposed to the gold standard pneumotachograph-derived ventilation measures. While it is extremely common to use nasal pressure to approximate ventilation in phenotyping studies [10, 58] and prior studies assessing the ventila- tory response to arousal have also analysed nasal pressure in this way [15, 49, 50], it remains possible that different results would be obtained with gold-standard measure- ments. Finally, only a portion of participants had data available for ventilatory response to arousal calculation, and as such the numbers in each subgroup were low. How- ever, the number of arousals included was quite large at over 200 reducing variability. Ultimately further replica- tion in larger, clinical populations with larger samples will be required to confirm the observation of elevated ventila- tory response to arousal from sleep in people with PTSD symptoms.

  The ventilatory response to arousal from sleep is elevated in young individuals with post-traumatic stress disorder symptoms · 2026 · DOI

• occlusions remains unclear [21,22] several studies have suggested that a mouth breathing and pharyngeal airway impairment are also Lakra et al.

  Evaluation of Sagittal Airway Dimensions in Various Skeletal Pattern and Its Correlation with Obstructive Sleep Apnea –A Cephalometric Study · 2026 · DOI

• Future research should explore the utility of lower-dose CT protocols or non-ionizing alternatives such as MRI for anatomical phenotyping. Several limitations of this study should be acknowl- edged.

  Three-dimensional upper airway phenotyping and OSA severity: a CT-based study · 2026 · DOI

• Several limitations should be acknowledged. First, mis- classification and detection bias cannot be fully excluded. Diagnostic accuracy and coding practices may vary across institutions, and patients with OSA may undergo more frequent medical evaluations and diagnostic testing, increasing the likelihood that incident diseases are identi- fied during follow-up. As a result, some of the observed associations may partly reflect differences in healthcare utilization and disease ascertainment rather than true differences in disease occurrence. In addition, key sleep- specific variables and important lifestyle-related con- founders, including smoking intensity, physical activity, and diet, are not consistently captured in structured elec- tronic health record data. Propensity score matching was restricted to age and sex, while other relevant clinical and lifestyle-related confounders, such as obesity, smoking, alcohol use, baseline metabolic status, and comorbid- ity burden, were not included in the matching process. Accordingly, residual confounding cannot be excluded and may have influenced the reported effect estimates. This is particularly relevant for the overweight/obesity outcome, as obesity is closely linked to both the develop- ment and diagnosis of OSA. Second, outcomes were assessed over a 5-year follow- up period, which may be insufficient to capture long- latency processes such as carcinogenesis for certain tumor types. In addition, OSA was identified using ICD- 10 coding only, which may have introduced diagnostic misclassification, and no information on disease sever- ity, hypoxemia burden, or treatment status was available. Therefore, severity-dependent associations and poten- tial dose–response relationships could not be examined. Moreover, OSA status and treatment exposure were modeled as baseline variables, although both may change over time, potentially introducing unmeasured time- varying confounding. Finally, undiagnosed OSA in the control group repre- sents a further source of bias. Because OSA is frequently underdiagnosed, some individuals classified as controls may have had unrecognized disease. In addition, both cohorts were restricted to hospitalized patients, and the study population may therefore not be representative of the broader OSA population. This may have introduced selection bias and limits the generalizability of the find- ings, particularly to patients with milder disease man- aged exclusively in outpatient settings. These limitations should be considered when interpret- ing the magnitude and generalizability of the observed associations.

  Is obstructive sleep apnea a driver of cancer and chronic disease risk? A real-world analysis of over 3 million patients · 2026 · DOI

• Approximately one-third of patients showed unexpected mismatch between pAHI3% and HB values; future investigations should identify the physiological, demographic, and sleep architecture variables that explain this intra-stratum variability to refine OSA endophenotyping.

  Hypoxic burden calculation in patients with obstructive sleep apnea diagnosed by peripheral arterial tonometry: diagnostic accuracy and clinical implications · 2026 · DOI

• PAT-HSAT hypoxic burden measurements were not directly compared against polysomnography-derived oxygen desaturation indices; future multicentre studies incorporating PSG as a reference standard are needed to confirm diagnostic accuracy and comparability across testing modalities.

  Hypoxic burden calculation in patients with obstructive sleep apnea diagnosed by peripheral arterial tonometry: diagnostic accuracy and clinical implications · 2026 · DOI

• Outcome-based analyses linking HB thresholds to longitudinal clinical outcomes (cardiovascular events, mortality, treatment response) were beyond the study scope; prospective multicentre cohort studies with long-term follow-up are needed to establish prognostic value and clinical utility of HB in risk stratification.

  Hypoxic burden calculation in patients with obstructive sleep apnea diagnosed by peripheral arterial tonometry: diagnostic accuracy and clinical implications · 2026 · DOI

• The study population resided at moderate altitude (1,500–2,600 m), which influences baseline oxygen saturation and hypoxaemic metric distribution; future studies must validate HB thresholds and clinical utility across populations at different altitudes and sea-level conditions.

  Hypoxic burden calculation in patients with obstructive sleep apnea diagnosed by peripheral arterial tonometry: diagnostic accuracy and clinical implications · 2026 · DOI

Most-cited papers in Obstructive Sleep Apnea Research

• The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults · New England Journal of Medicine · 1993 · 7,583 citations
• Obstructive Sleep Apnea as a Risk Factor for Stroke and Death · New England Journal of Medicine · 2005 · 2,443 citations
• Diagnosis and Management of Obstructive Sleep Apnea · JAMA · 2020 · 1,295 citations
• Diagnosis and Management of Childhood Obstructive Sleep Apnea Syndrome · PEDIATRICS · 2012 · 1,251 citations
• Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity · New England Journal of Medicine · 2024 · 655 citations
• Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women · JAMA · 2011 · 639 citations
• PROLONGED APNEA AND THE SUDDEN INFANT DEATH SYNDROME: CLINICAL AND LABORATORY OBSERVATIONS · PEDIATRICS · 1972 · 425 citations
• Association of Hypertension and Sleep-Disordered Breathing · Archives of Internal Medicine · 2000 · 408 citations
• Neurobehavioral Implications of Habitual Snoring in Children · PEDIATRICS · 2004 · 394 citations
• Obstructive Sleep Apnea in Children With Down Syndrome · PEDIATRICS · 1991 · 366 citations

Most recent work

• Proximal Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in the OSPREY Study · Annals of Internal Medicine · 2026
• Somesthetic perception of upper airway airflow in individuals with and without obstructive sleep apnea: a prospective study · Sleep Science and Practice · 2026
• The ventilatory response to arousal from sleep is elevated in young individuals with post-traumatic stress disorder symptoms · Journal of Clinical Sleep Medicine · 2026
• Artificial intelligence and sleep medicine · Respiratory Medicine · 2026
• REM-Obstructive Sleep Apnea: Clinical Characteristics and Cardiovascular, Cognitive, Neurobehavioral, and Metabolic Implications · Current Sleep Medicine Reports · 2026
• Comparative effects of weight-loss diet, exercise training, respiratory muscle training, and oropharyngeal muscle training in obstructive sleep apnea: a systematic review and network meta-analysis · Frontiers in Medicine · 2026
• Bridging the gap in sleep health: a study of obstructive sleep apnoea ( <scp>OSA</scp> ) in First Nations Australians residing in South East Queensland · Internal Medicine Journal · 2026
• Hypoxic burden calculation in patients with obstructive sleep apnea diagnosed by peripheral arterial tonometry: diagnostic accuracy and clinical implications · Sleep Science and Practice · 2026
• Functional Airway Medicine: Integrating Otolaryngology, Dentofacial Structures, Trauma, and Sleep in a Multidisciplinary Clinical Model · IECCMEXICO · 2026
• Predictive value of the atherogenic index of plasma for incident hypertension in patients with obstructive sleep apnea · BMC Pulmonary Medicine · 2026

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