Improving current diagnostics and therapy in obstructive sleep apnea: Towards a patient-centered and personalized approach

Abstract

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by recurrent partial or complete collapse of the upper airway during sleep, leading to intermittent hypoxia and sleep fragmentation. OSA can significantly impact quality of life, daytime functioning, and is associated with cardiovascular and neurological comorbidities. This thesis addresses several challenges in the clinical management of OSA. Treatment outcomes vary considerably between patients, highlighting the need for better predictors for therapeutic success. Also, the respiratory objective parameters collected during sleep studies to measure OSA severity seem to not always correspond with patient-reported symptoms. A major focus of this thesis is the role of drug-induced sleep endoscopy (DISE) in the assessment and treatment of OSA. DISE allows direct visualization of upper airway collapse during pharmacologically induced sleep and is increasingly used in patient selection for upper airway stimulation therapy (UAS). Retrospective analyses demonstrated that specific collapse patterns, including a specific combined anteroposterior and concentric velar collapse pattern and a floppy epiglottis, do not negatively affect UAS treatment outcomes. These findings, describing specific collapse patterns, demonstrate that current classifications used during DISE, may not capture the full complexity of the upper airway. A more detailed classification of upper airway collapse may improve the identification of collapse patterns associated with treatment succes or failure, thereby improving the prediction of treatment response. The DISE is also used in those patients that already being implanted with UAS, but are non-responders of the therapy. Performing DISE with active stimulation enables visualization of residual obstruction, giving the opportunity to improve stimulation settings or identify complementary treatment options such as oral appliance therapy or upper airway surgery. This exploratory studie showed improved outcomes in a subset of previously non-responders. The predictive value of DISE for oral appliance therapy (OAT) was evaluated in a prospective study comparing different mandibular advancement manoeuvres during DISE. A positive jaw-thrust manoeuvre was associated with a lower residual apnea–hypopnea index (AHI) after treatment. However, a negative jaw-thrust could not reliably identify patients who would fail OAT. Therefore, routine DISE before OAT cannot currently be recommended. Also, this thesis explores the relationship between objective sleep study parameters and patient-reported outcomes. UAS was shown to alter not only the overall AHI but also the relative distribution of apneas and hypopneas, indicating that AHI alone may not fully reflect changes in breathing patterns during sleep. Furthermore, patient-reported measures of sleepiness and daytime functioning showed no clinical relevant correlation with traditional respiratory parameters. These findings emphasize the limitations of current outcome measures and support ongoing efforts to develop more clinically meaningful metrics of OSA severity and treatment response. Overall, this thesis contributes to a better understanding of the opportunities and limitations of DISE and the complex relationship between respiratory parameters and patient symptoms in OSA. The future should progress towards a patient-centered and personalized OSA approach. To achieve this we need improved outcome measures to reflect the clinical impact of the disease and a better understanding of patient-specific factors influencing treatment response.