Obstructive sleep apnea (OSA) is a common sleep disorder associated with intermittent hypoxia, systemic inflammation, oxidative stress, and an increased risk of cardiovascular and metabolic diseases. Current diagnostic methods are effective but have limited availability and do not adequately predict disease burden or treatment response.
The purpose of this study is to identify and validate blood biomarkers that may improve the screening, diagnosis, risk stratification, and monitoring of adults with OSA. A total of 120 participants will undergo clinical evaluation and overnight polysomnography. Participants with moderate-to-severe OSA will be randomly assigned to either immediate or delayed positive airway pressure (PAP) therapy, while participants without OSA will serve as controls. Blood samples will be collected at predefined time points and analyzed for inflammatory, metabolic, oxidative stress, and other candidate biomarkers.
The study aims to determine which biomarkers are associated with OSA severity and how they change in response to PAP therapy. The results may contribute to the development of more accessible and personalized diagnostic and monitoring strategies for patients with OSA.
Age 18 to 65 years.
Moderate or severe obstructive sleep apnea confirmed by overnight polysomnography (apnea-hypopnea index [AHI] ≥15 events/hour).
Willing and able to provide written informed consent.
Willing to undergo repeated blood sampling and study assessments.
Mild obstructive sleep apnea (AHI 5 to <15 events/hour).
Central sleep apnea.
Previous treatment for obstructive sleep apnea within the previous 3 months.
Body mass index (BMI) ≥40 kg/m².
Parallel
Positive Airway Pressure (PAP) Therapy
DevicePositive airway pressure (PAP) therapy will be administered according to current clinical practice guidelines for the treatment of obstructive sleep apnea. PAP settings will be individually titrated based on clinical assessment and sleep study findings to ensure effective treatment. Participants assigned to PAP therapy will use the device during sleep for the duration specified in the study protocol. Adherence to therapy will be monitored using device-recorded usage data.
Difference in blood biomarker concentrations between participants with obstructive sleep apnea (OSA) and non-OSA controls at baseline
Comparison of baseline serum and plasma concentrations of a predefined panel of circulating protein biomarkers (osteoprotegerin, cardiotrophin-1, chitinase-3-like protein 1/YKL-40, CRP, HbA1c, erythropoietin, thioredoxin, PD-L1) and a predefined multiplex panel of 48 cytokines, chemokines and growth factors, measured by ELISA and multiplex ELISA (Luminex), between adults with moderate-to-severe OSA (AHI \>=15) and non-OSA controls (AHI \<5) defined by polysomnography. Results will be reported in assay-appropriate units, including pg/mL, ng/mL, mg/L, or percentage, as applicable.
Change in blood biomarker concentrations in OSA participants after positive airway pressure (PAP) therapy.
Change from baseline in serum and plasma concentrations of the predefined biomarker panel after positive airway pressure (PAP) therapy. In the Early Treatment Group change is assessed after 3 and 6 months of continuous PAP; in the Delay-TG after 3 months of PAP delivered between months 3 and 6. Aim: determine whether and to what degree biomarker values change in response to standard OSA treatment.
Correlation between baseline blood biomarker concentrations and OSA severity (AHI)
Correlation between baseline concentrations of the studied blood biomarkers and OSA severity expressed by the apnea-hypopnea index (AHI), as well as mean and lowest nocturnal oxygen saturation, in OSA participants. Goal: evaluate suitability of biomarkers for grading OSA severity.
Normalization of blood biomarker concentrations toward control values after PAP therapy in OSA participants.
Comparison of post-PAP-treatment biomarker concentrations in OSA participants (Early-TG and Delay-TG) with the enrollment values of the non-OSA control group, to assess whether treatment shifts biomarker values toward those of healthy controls. Goal: identify biomarkers specific to OSA-related hypoxia that approach the concentrations observed in participants without OSA.
Effect of PAP treatment duration (3 vs 6 months) on blood biomarker concentrations
Assessment of the impact of PAP treatment duration on biomarker values: (a) comparison of post-treatment values between the Early Treatment Group (6 months of PAP) and the Delay Treatment Group (3 months of PAP); (b) within Early-TG, comparison of values after 3 versus 6 months to evaluate whether changes become more robust with continued treatment. Goal: determine whether longer therapy produces greater biomarker change.
Stability of blood biomarker concentrations in untreated OSA (3-month observation period).
Comparison of biomarker concentrations in the Delay-TG between baseline and after the 3-month observation period without any treatment, to verify that biomarker values do not change spontaneously in the absence of PAP therapy. Serves as the internal untreated reference for the treatment effect.
Differences in blood biomarker concentrations between moderate and severe OSA subgroups.
Comparison of biomarker concentrations between participants with moderate OSA (15\<=AHI\<30) and severe OSA (AHI\>=30) at baseline and in response to PAP therapy.
Differences in blood biomarker concentrations between BMI categories (normal weight, overweight, obese).
Comparison of biomarker concentrations between body-mass-index categories (normal \<25, overweight 25-\<30, obese \>=30) at baseline and in response to PAP therapy, to assess whether biomarker profile and treatment response differ by weight category.
Differences in blood biomarker concentrations between female and male participants.
Comparison of biomarker concentrations between female and male participants at baseline and in response to PAP therapy, to assess sex-related differences in biomarker profile and treatment response.
Concentrations of oxidative stress biomarkers in OSA participants and controls
Assessment of protein, lipid and DNA oxidation products: advanced oxidation protein products (AOPP, colorimetric method), ischemia-modified albumin, advanced glycation end products, 3-nitrotyrosine, 4-hydroxynonenal, 8-isoprostanes and 8-hydroxy-2-deoxyguanosine (ELISA), compared between OSA and controls at baseline and before versus after PAP therapy.
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Medical University of Bialystok
Lead sponsor
National Science Centre, Poland
Collaborator
