Obstructive Sleep Apnea and Telomere Length

Obstructive sleep apnea (OSA) is a highly prevalent and morbid sleep disorder. Among the factors associated with its pathophysiology, the role of intermittent hypoxia stands out, contributing to the development of oxidative stress and inflammation. It is known that cumulative levels of these factors negatively influence the final portion of the DNA, known as telomere. In this sense, the investigators hypothesize that OSA is capable of accelerating aging process through telomere shortening mediated by inflammatory and oxidative markers. Thus, the aim of this study is to investigate the effect of OSA and its treatment with CPAP on the variation of telomere length and their associated mechanisms. For this, a randomized, double-blind, sham-controlled clinical study with 6 months duration will be conducted. We will recruit male participants with OSA diagnosis (apnea-hypopnea indexe15/hour), aged between 35-65 years and body mass index<35 kg/m2, which will be randomized to use CPAP or sham-CPAP for 6 months. Participants will visit the laboratory 7 times (baseline and after 1, 2, 3, 4, 5 and 6 months) and will be submitted to clinical and otorhinolaryngological evaluation, sleep questionnaires, polysomnography and blood collection for DNA and extraction and measurement of telomere length, as well as the expression of telomerase and oxidative and inflammatory markers (ADMA, homocysteine, cysteine, TBARS, 8-oxodG, TNF-a, IL-6 and IL-10). This project aims to contribute to the elucidation of the effect of OSA on telomere length maintenance, as well as the adjacent mechanisms to this relationship.

All participants in continuous airway positive pressure arm will use CPAP (model S10-Resmed®) with expiratory relief and nasal mask.

Individuals in SHAM continuous airway positive pressure arm will use CPAP (model S7-Resmed®) with expiratory relief and nasal mask. The Sham-CPAP consists of a modified CPAP so that the pressure in the mask was less than 1 cm H2O. In this study, the Sham-CPAP equipment includes an increase in the expiratory orifice of the CPAP mask to eliminate airflow resistance, and a resistor with a small orifice was placed between the CPAP and the circuit. The noise produced by the ventilator and the airflow through the mask will be very similar to that of the effective CPAP. The diameter of the expiratory orifice was 10 cm H2O, and a 4 mm diameter resistor was placed between the trachea and the CPAP flow generator.

The continuous airway positive pressure will be used as the gold-standard treatment for obstructive sleep apnea for 6 months

Inclusion Criteria: body mass index (BMI) of less than 35kg/m2 age between 35 and 65 years diagnosed by laboratory polysomnography with moderate to severe OSA (apnea-hypopnea index, AHI≥20 events/hour of sleep) Exclusion Criteria: illiteracy participants with more than 50% of the respiratory events obtained in the polysomnography exam being central apneas participants with central AHI>5 events/hour of sleep participants with sleepiness, measured by the Epworth sleepiness scale≥14 participants with severe otorhinolaryngological diseases that preclude the use of CPAP (severe nasal septum deviation, severe nasal turbinate hypertrophy, marked palatine and/or adenoid hypertrophy) abuse of alcohol or chronic use of psychoactive drugs participants with decompensated clinical, neurological or psychiatric illness participants with other sleep disorders; participants who had already undergone previous OSA treatments