Abstract

Introduction: Sleep-disordered breathing is a societal problem due to its high prevalence and complex impact on human health. The inflammasome, a multiprotein complex in cells of the immune system, is a critical regulator of inflammatory responses and may hold the key to understanding the relationship between inflammation, atherosclerosis and sleep disorders. Exosomes, small vesicles that are secreted by almost all cells into extracellular fluids, may serve as carriers of molecular signals, including those involved in inflammatory processes. The detection of markers of inflammation using isolated exosomes from peripheral blood samples of patients diagnosed with obstructive sleep apnea (OSA) is more specific and accurate compared to the detection of markers in whole blood. Hypothesis: the inflammasome plays an important role in the inflammatory processes and lipidome disorders associated with OSA. We hypothesize that markers of inflammation and lipid profiles may help identify and stratify patients with OSA. In addition, these markers may provide insight for personalized therapy and suggest potential therapeutic targets.

Methodology: 1. initial examination: overnight sleep monitoring (polysomnography), anthropometry, patient history, sleepiness measure (Epworth Sleepiness Scale). Classification of patients into healthy controls (negative polysomnography result) and OSA individuals indicated for CPAP therapy. 2. blood tests: serum analysis and blood tests. Serum analysis will be included as part of the test as a basic standard of care. A portion of the serum sample used for lipidomic analysis (CERT-2), markers of chronic inflammation, particularly IL-1ß, IL-18, ASC oligomers, caspase-1, AIM, NLRC4 and NLRP1, and exosome isolation 3. follow-up and second blood test: after 3 months in individuals with OSA – same tests as in point 2. In parallel, evaluation of treatment adherence rate and efficacy (including reevaluation of Epworth Sleepiness Scale).

General project objective

Personalised medicine promises to identify specific biomarkers, understand molecular mechanisms and develop targeted therapies for OSA patients. Therefore, the aim of the project proposal is to characterise OSA patients in detail in order to identify therapeutic targets. This study will compare selected markers (see objectives 1-4) in healthy controls and patients before and after CPAP treatment. Objectives of the project: 1. Comprehensive analysis of patients‘ sleep. 2. Determination of the level of regulatory molecules and markers of chronic inflammation 3. Analysis of exosomes from patients‘ blood and identification of specific molecular markers. 4. Performing a complex cluster analysis from the measured and obtained data.