scholarly journals Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea

2020 ◽  
Vol 21 (6) ◽  
pp. 2233
Author(s):  
David Sanz-Rubio ◽  
Arianne Sanz ◽  
Luis Varona ◽  
Rosa Bolea ◽  
Marta Forner ◽  
...  

Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.

2013 ◽  
Vol 8 ◽  
Author(s):  
Bilal Arik ◽  
Mehmet Fatih Inci ◽  
Cesur Gumus ◽  
Kenan Varol ◽  
Meltem Refiker Ege ◽  
...  

Background: Both obstructive sleep apnea syndrome (OSAS) and coronary artery calcification (CAC) are considered to be related with the presence of coronary artery disease (CAD). In this study we evaluate the association between OSAS and presence of subclinical atherosclerosis assessed by tomographic coronary calcium score in patients who had OSAS but no history of known CAD. Methods: Seventy-three patients who were asymptomatic for CAD and had suspected OSAS were referred to overnight attended polysomnography. Patients were classified into 4 groups according to the Apnea-Hypopnea Index (AHI). All patients underwent computed tomographic examination for tomographic coronary calcification scoring. Physical examination, sleep study recordings, complete blood count and serum biochemistry were obtained from all patients. Results: In the whole group, AHI levels were weakly correlated with coronary calcium score (r = 0.342, p = 0.003) and body mass index (r = 0.337, p = 0.004), moderately correlated with basal oxygen saturation (r = −0.734, p < 0.001), and strongly correlated with oxygen desaturation index (r = 0.844, p < 0.001). In an univariate analysis, age, AHI, basal oxygen saturation, and oxygen desaturation index were associated with CAC in patients with OSAS. In a multiple logistic regression model, age (OR 1.108,%95 CI 1.031-1.191, p = 0.005) and AHI (OR 1.036,% 95 CI 1.003-1.070, p = 0.033) were only independent predictors of CAC in patients with OSAS with a sensitivity of 88.9% and 77.8% and a specificity of 54.3% and 56.5% respectively. Conclusions: Our findings suggest that in patients with moderate or severe OSAS and advanced age, physicians should be alert for the presence of subclinical atherosclerosis.


2020 ◽  
Vol 103 (8) ◽  
pp. 725-728

Background: Lifestyle modification is the mainstay therapy for obese patients with obstructive sleep apnea (OSA). However, most of these patients are unable to lose the necessary weight, and bariatric surgery (BS) has been proven to be an effective modality in selected cases. Objective: To provide objective evidence that BS can improve OSA severity. Materials and Methods: A prospective study was conducted in super morbidly obese patients (body mass index [BMI] greater than 40 kg/m² or BMI greater than 35 kg/m² with uncontrolled comorbidities) scheduled for BS. Polysomnography (PSG) was performed for preoperative assessment and OSA was treated accordingly. After successful surgery, patients were invited to perform follow-up PSG at 3, 6, and 12 months. Results: Twenty-four patients with a mean age of 35.0±14.0 years were enrolled. After a mean follow-up period of 7.8±3.4 months, the mean BMI, Epworth sleepiness scale (ESS), and apnea-hypopnea index (AHI) significantly decreased from 51.6±8.7 to 38.2±6.8 kg/m² (p<0.001), from 8.7±5.9 to 4.7±3.5 (p=0.003), and from 87.6±38.9 to 28.5±21.5 events/hour (p<0.001), respectively. Conclusion: BS was shown to dramatically improve clinical and sleep parameters in super morbidly obese patients. Keywords: Morbid obesity, Bariatric surgery, Obstructive sleep apnea (OSA)


ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London

<b><i>Objective:</i></b> The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. <b><i>Methods:</i></b> Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. <b><i>Results:</i></b> By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (<i>p</i> &#x3c; 0.05), while the Apnea-Hypopnea Index (AHI) changed little (<i>p</i> = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all <i>p</i> &#x3c; 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (<i>p</i> &#x3c; 0.05), except with the AHI (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.


2021 ◽  
Vol 10 (7) ◽  
pp. 1387
Author(s):  
Raphael Boneberg ◽  
Anita Pardun ◽  
Lena Hannemann ◽  
Olaf Hildebrandt ◽  
Ulrich Koehler ◽  
...  

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.


SLEEP ◽  
2021 ◽  
Author(s):  
Ankit Parekh ◽  
Korey Kam ◽  
Anna E Mullins ◽  
Bresne Castillo ◽  
Asem Berkalieva ◽  
...  

Abstract Study Objectives Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. Methods Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. Results Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2); %total sleep time, p &lt; 0.001) with a small increase in apnea–hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3); p &lt; 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p &lt; 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. Conclusions Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.


Author(s):  
Satoru Tsuiki ◽  
Takuya Nagaoka ◽  
Tatsuya Fukuda ◽  
Yuki Sakamoto ◽  
Fernanda R. Almeida ◽  
...  

Abstract Purpose In 2-dimensional lateral cephalometric radiographs, patients with severe obstructive sleep apnea (OSA) exhibit a more crowded oropharynx in comparison with non-OSA. We tested the hypothesis that machine learning, an application of artificial intelligence (AI), could be used to detect patients with severe OSA based on 2-dimensional images. Methods A deep convolutional neural network was developed (n = 1258; 90%) and tested (n = 131; 10%) using data from 1389 (100%) lateral cephalometric radiographs obtained from individuals diagnosed with severe OSA (n = 867; apnea hypopnea index > 30 events/h sleep) or non-OSA (n = 522; apnea hypopnea index < 5 events/h sleep) at a single center for sleep disorders. Three kinds of data sets were prepared by changing the area of interest using a single image: the original image without any modification (full image), an image containing a facial profile, upper airway, and craniofacial soft/hard tissues (main region), and an image containing part of the occipital region (head only). A radiologist also performed a conventional manual cephalometric analysis of the full image for comparison. Results The sensitivity/specificity was 0.87/0.82 for full image, 0.88/0.75 for main region, 0.71/0.63 for head only, and 0.54/0.80 for the manual analysis. The area under the receiver-operating characteristic curve was the highest for main region 0.92, for full image 0.89, for head only 0.70, and for manual cephalometric analysis 0.75. Conclusions A deep convolutional neural network identified individuals with severe OSA with high accuracy. Future research on this concept using AI and images can be further encouraged when discussing triage of OSA.


Entropy ◽  
2021 ◽  
Vol 23 (3) ◽  
pp. 267
Author(s):  
Duan Liang ◽  
Shan Wu ◽  
Lan Tang ◽  
Kaicheng Feng ◽  
Guanzheng Liu

Obstructive sleep apnea (OSA) is associated with reduced heart rate variability (HRV) and autonomic nervous system dysfunction. Sample entropy (SampEn) is commonly used for regularity analysis. However, it has limitations in processing short-term segments of HRV signals due to the extreme dependence of its functional parameters. We used the nonparametric sample entropy (NPSampEn) as a novel index for short-term HRV analysis in the case of OSA. The manuscript included 60 6-h electrocardiogram recordings (20 healthy, 14 mild-moderate OSA, and 26 severe OSA) from the PhysioNet database. The NPSampEn value was compared with the SampEn value and frequency domain indices. The empirical results showed that NPSampEn could better differentiate the three groups (p < 0.01) than the ratio of low frequency power to high frequency power (LF/HF) and SampEn. Moreover, NPSampEn (83.3%) approached a higher OSA screening accuracy than the LF/HF (73.3%) and SampEn (68.3%). Compared with SampEn (|r| = 0.602, p < 0.05), NPSampEn (|r| = 0.756, p < 0.05) had a significantly stronger association with the apnea-hypopnea index (AHI). Hence, NPSampEn can fully overcome the influence of individual differences that are prevalent in biomedical signal processing, and might be useful in processing short-term segments of HRV signal.


Author(s):  
Michał Harańczyk ◽  
Małgorzata Konieczyńska ◽  
Wojciech Płazak

Abstract Purpose Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. Methods NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. Results Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S′ ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. Conclusion Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Narongkorn Saiphoklang ◽  
Kanyada Leelasittikul ◽  
Apiwat Pugongchai

AbstractContinuous positive airway pressure (CPAP) is simple and effective treatment for obstructive sleep apnea (OSA) patients. However, the CPAP prediction equation in each country is different. This study aimed to predict CPAP in Thai patients with OSA. A retrospective study was conducted in Thai patients, who OSA was confirmed by polysomnography and CPAP titration from January 2015 to December 2018. Demographics, body mass index (BMI), neck circumference (NC), Epworth sleepiness scale, apnea–hypopnea index (AHI), respiratory disturbance index (RDI), mean and lowest pulse oxygen saturation (SpO2), and optimal pressure were recorded. A total of 180 subjects were included: 72.8% men, age 48.7 ± 12.7 years, BMI 31.0 ± 6.3 kg/m2, NC 40.7 ± 4.1 cm, AHI 42.5 ± 33.0 per hour, RDI 47.1 ± 32.8 per hour, and lowest SpO2 77.1 ± 11.0%. Multiple linear regression analysis identified NC, BMI, RDI, and lowest SpO2. A final CPAP predictive equation was: optimal CPAP (cmH2O) = 4.614 + (0.173 × NC) + (0.067 × BMI) + (0.030 × RDI) − (0.076 × lowest SpO2). This model accounted for 50.0% of the variance in the optimal pressure (R2 = 0.50). In conclusion, a CPAP prediction equation can be used to explain a moderate proportion of the titrated CPAP in Thai patients with OSA. However, the CPAP predictive equation in each country may be different due to differences of ethnicity and physiology.Trial registration: TCTR20200108003.


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