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Title: The influence of oral appliances treatment on inflammatory and hemostatic markers in obstructive sleep apnea


Obstructive sleep apnea (OSA) caused by diminished patency of the upper airways with a maintenance of the respiratory effort is a (max 1400 znaków) common disease, affecting from 2 to 4% of the European population. OSA is characterized by repetitive episodes of apnea and hypopnea during sleep. Untreated OSA increases the risk of cardiovascular diseases, including myocardial infarction or ischemic stroke. The occurrence of chronic episodes of intermitted hypoxia and reoxygenation, together with sleep fragmentation and its regulatory mechanisms during OSA, lead to chronic systemic inflammation, which can accelerate the development of atherosclerosis. Increased blood hematocrit, elevated levels of fibrinogen and increased blood viscosity probably also play an important role in atherothrombosis in OSA patients. The gold standard of severe OSA treatment is the use of the continuous positive airway pressure (CPAP). In the mild and moderate forms other therapeutic options are often indicated, including oral appliances. Till today, it has been demonstrated that treatment with oral appliance ameliorates the polisomnographic features of OSA, decreases the subjective symptoms, improves endothelial function and autonomic cardiac modulation as well as diminishes arterial blood pressure. The aim of this study was to assess whether oral appliances influence the inflammatory and hemostatic mar ; kers in moderate OSA patients. Forty-six individuals were included into the open-label interventional study, carried out in 27 moderate OSA patients (24 men and 4 women) (OSA group) and 19 apparently healthy people who constituted the control group. The control group was well matched with the OSA group by the demographic variables, body mass index, arterial systolic and diastolic blood pressure and oxygen saturation. For the patients with moderate OSA the KlearwayTM oral appliance was individually made. In the OSA group the polisomnography examination, baseline laboratory tests, pulmonary function tests (spirometry) and the measurements of the inflammatory and hemostatic markers (fibrinogen, C-reactive protein [CRP], interleukin 1 beta [IL-1 ß], interleukin 10 [IL-10], interleukin 6 [IL-6], plasminogen activator inhibitor-1 [PAI-1], P-selectin, D-dimer, thrombin-antithrombin complex [TAT] and activated thrombin- activatable fibrinolysis inhibitor [TAFIa]) was carried out at baseline and then after 3 and 6 months of oral appliance treatment; in the control group the same procedures were performed twice at baseline and after 6 months of the study. A final analysis included 23 OSA patients and 19 healthy subjects. As compared to the control group, in the moderate OSA group the higher baseline levels of IL-1 ß (0.34 [pg/ml] vs 0.24; p=0.03), IL- 10 (5.69 [pg/ml] vs 3.96; p=0.01), P ; AI- 1 (28.44 [ng/ml] vs 19.32; p=0.02), fibrinogen (3.85 [g/l] vs 3.30; p=0.02) and TAFIa (81.23 [pmol/l] vs 50.19; p=0.02) were found. Strong positive correlations in the OSA group were observed between PAI-1 and both IL-1ß (R=0.76, p<0.0001) and IL-10 (R=0.76, p<0.0001). The two latter parameters were also correlated (R=0.8, p<0.0001). Similarly the significant correlations were found between CRP and both TAT (R=-0.4; p=0.04) and IL-6 (R=0.44; p=0.02). The use of oral appliances in the moderate OSA group caused a significant improvement in the polisomnographic features. A clinically important reduction in the apnea-hypopnea index from 25 per hour of sleep to 13.1 after 3 months (p=0.001) and to 7 after the following 3 months (p=0.02) was observed. The desaturation index gradually decreased from 21.5 to 14.3 after 3 months (versus baseline, p=0.003) and then to 8.1 after 6 months (p<0.0001). The time of oxygen saturation lower than 90% and 85% gradually decreased to 5.4 min (p<0.0001) and 0.3 min (p=0.03) after 6 months, respectively. The decrease of all markers elevated at baseline was found except fibrinogen levels., In the control group no changes of all parameters studied were observed after 6 months. In the OSA group the decrease of IL-1 ß concentrations after the first 3 months from 0.35 pg/ml to 0.19 pg/ml (p<0.001) was noted. In the following 3 months this parameter di ; d not change (p=0.12), similarly to the control group (p=0.61). After the first 3 months of oral appliance treatment, a 43% decrease of IL-10 concentrations close to the level of statistical significance was found (p=0.06) without further reduction after the next 3 months (p=0.66). The concentration of PAI-1 during a 6-month treatment with oral appliance was reduced to 19.89 ng/ml (29.6 %) (p=0.008). Interestingly, the concentration of TAFIa also decreased in the OSA group during oral appliance treatment from 81.23 pmol/l to 43.43 after 6 months (p=0.001), which accounts for 50.5% of the initial concentration, and this fall was substantial already after the first 3 months (p=0.029). A significant correlation between IL-1ß and PAI-1 concentrations at the 3 time points was found. Similarly there was an association of TAFIa concentration and AHI as well as the oxygen saturation lower than 90%. Other markers of inflammation, including CRP, and those of hemostasis, including thrombin generation, remained unaltered during 6 months of oral appliance use. Summarizing, this study confirms the effectiveness of treatment with oral appliances in the moderate OSA, which is corraborated by a marked improvement of the polisomnographic parameters. Importantly, for the first time it has been shown that the treatment with oral appliances in moderate OSA patients decreases the concentrations of I ; L-1 ß and IL-10 and produces the profibrinolytic effect, which demonstrates novel, as yet unknown effects of the oral appliance treatment. The original observation is also the presence of increased TAFIa concentrations in the moderate OSA, which were reduced after oral appliance treatment. These observations increase our knowledge about the mechanisms which may favuor the development of atherosclerosis and thrombosis in moderate OSA and that these mechanisms can be effectively modified by oral appliance treatment.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

stomatologia ; choroby układu krążenia

Degree grantor:

Wydział Lekarski


Undas, Anetta

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Last modified:

Mar 15, 2023

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Nov 21, 2012

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ZB-113622 Mar 15, 2023


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