P060 Hypoxia-induced overexpression of Rev-Erb-alpha and NPAS2 proteins in obstructive sleep apnea patients - possible mechanism of DM2 development

Abstract Circadian clocks are endogenous coordinators of 24-hour behavioral and molecular rhythms, which disruption may be caused by obstructive sleep apnea (OSA). It is composed of a set of genes, function as activators (CLOCK, BMAL) or repressors (PER, CRY). Neuronal PAS Domain Protein 2 (NPAS2) can substitute CLOCK in its function. Orphan nuclear receptor (Rev-Erb-α) is another protein supporting the CLOCK-BMAL1 complex, forming the loop which helps to regulate their expression. There are studies suggesting the significant influence of circadian disruption mediated via NPAS2 and Rev-Erb-α on DM2 development. The aim of the study was to determine the role of NPAS2 and Rev-Erb-α in DM2 for OSA patients. All participants underwent polysomnography (PSG) examination. Based on apnea-hypopnea index accompanied by clinical data the recruited individuals (n=40) were assigned to one from 3 groups: OSA (severe OSA, no DM2; n=17), DM2 (severe OSA + DM2; n=7) and control group (no OSA, no DM2; n=16). Serum protein levels of Rev-Erb-α and NPAS2 were assessed with ELISA immunoassay. Analysis between the groups revealed the statistically significant difference only in NPAS2 protein level (p=0.037). Further post-hoc analysis revealed significant differences between OSA and the control group (p=0.017). Moreover, a statistically significant correlation between AHI and NPAS2 serum protein level was observed (r=-0.478, p=0.002). NPAS2 protein levels are associated with a number of apneas and hypopneas during the REM phase of sleep and might have a significant role in the development of OSA complications. However, further studies are needed to understand its role.

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0170 Association of HIF-1 Alpha and Beta Subunits with Clock and BMAL1 Proteins in Obstructive Sleep Apnea Patients

SLEEP ◽

10.1093/sleep/zsaa056.168 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A67-A67

Author(s):

A Gabryelska ◽

M Sochal ◽

S Turkiewicz ◽

P Bialasiewicz

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Circadian Clock ◽

Hypoxia Inducible Factor ◽

Study Groups ◽

Oxygen Metabolism ◽

Apnea Hypopnea Index ◽

Protein Levels ◽

Obstructive Sleep ◽

Significant Difference

Abstract Introduction Obstructive sleep apnea (OSA) is a chronic condition that is characterized by intermittent hypoxia. Key regulator of oxygen metabolism is hypoxia inducible factor (HIF), which consists of oxygen sensitive subunit and continuously produced subunit. Circadian clock is composed of set of genes, which function as activators - CLOCK and BMAL 1, who similarly to HIF are basic helix-loop-helix-PER-ARNT-SIM transcription factors. Therefore, the aim of the study was to assess the relationship between HIF-1alpha, HIF-1beta, CLOCK, BMAL1 and polysomnography (PSG) variables in healthy individuals and severe OSA patients. Methods The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI<5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. HIF-1alpha, HIF-1beta, CLOCK and BMAL1 protein concertation measurements were performed using ELISA. Results Significant difference was observed in the following protein measurements between study groups: evening and morning HIF-1 (p=0.020 and p=0.043, respectively), evening HIF-1alpha (p=0.047), evening and morning CLOCK (p=0.037 and p=0.019, respectively) and morning BMAL1 (p=0.016). No differences were observed between morning and evening protein levels in both groups. Evening HIF-1beta corraleted with evening CLOCK and morning BMAL1 (R=0.511, p=0.21 and R=0.594, p=0.006, respectively), while morning HIF-1 with evening BMAL1 (R=474, p=0.35). Furthermore, evening and morning HIF-1 correlated with evening BMAL1 (R=564, p=0.010 and R=0.689, p=0.001, respectively). Additionally, morning CLOCK and BMAL1 correlated with AHI (R=0.510, p=0.022 and R=0.560, p=0.010, respectively) and desaturation index (R=0.487, p=0.209 and R=0.570, p=0.009, respectively). Conclusion There is significant correlation between both subunits of HIF-1 protein and circadian clock proteins: CLOCK and BMAL1, which further correlate with increased disease severity. This suggests OSA patients are in risk of circadian clock disruption due to present hypoxia. Support The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931.

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Creatinine Clearance in Patients with Obstructive Sleep Apnea

Medical Laboratory Technology Journal ◽

10.31964/mltj.v7i1.378 ◽

2021 ◽

Vol 7 (1) ◽

pp. 59

Author(s):

Seda Beyhan Sagmen ◽

Nesrin Kiral ◽

Ali Fidan ◽

Elif Torun Parmaksiz ◽

Coskun Dogan ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Endothelial Dysfunction ◽

Creatinine Clearance ◽

Control Group ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Significant Difference ◽

Group 2 ◽

Group 1

During an apnea, hemodynamic complications such as hypoxemia, a rise in systemic and pulmonary arterial pressure, and changes in heart rate occur in patients with obstructive sleep apnea (OSA). Potential mechanisms of OSA-associated renal dysfunction include renal hypoxia, hypertension, endothelial dysfunction. Hypertension is common in patients with OSA. This study aims to assess OSA patients' renal functions and investigate the creatinine clearance (CC) values across OSA patients with and without hypertension. The study included 530 individuals with OSA and 60 individuals with an apnea-hypopnea index (AHI) of <5. CC calculated with the Cockcroft-Gault Equation. Patients with OSA divide into two groups as the group of patients with hypertension (HT) (group 1) and without HT (group 2). The study included 339 (64%) male and 191 (36%) female patients. It found that 32.4% of OSA patients had HT (Group 1). There was a significant difference in CC and urea levels between groups 1 and 2 (p<0.001; p=0.005). While CC was low in the OSA group, CC values were not statistically significantly different between the OSA patients and the control group (p>0.05). A statistically significant difference was detected in urea and creatinine levels between the OSA and control groups (p=0.005; p=0.012). Creatinine clearance decreases in patients with OSA in the presence of HT. Patients with OSA often experience cardiovascular disorders, and glomerular endothelial dysfunction occurs in OSA patients.

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Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽

10.1159/000516243 ◽

2021 ◽

pp. 1-8

Author(s):

Lifeng Li ◽

Demin Han ◽

Hongrui Zang ◽

Nyall R. London

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Nasal Obstruction ◽

Upper Airway ◽

Apnea Hypopnea Index ◽

Nasal Surgery ◽

Subjective Sleep Quality ◽

Obstructive Sleep ◽

Significant Difference ◽

The Impact

Objective: 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. Methods: 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. Results: By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (p < 0.05), while the Apnea-Hypopnea Index (AHI) changed little (p = 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 p < 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (p < 0.05), except with the AHI (p > 0.05). Conclusion: 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.

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Effect of Cooling Irrigating Saline in Tongue Base Ablation in Obstructive Sleep Apnea

OTO Open ◽

10.1177/2473974x21989599 ◽

2021 ◽

Vol 5 (1) ◽

pp. 2473974X2198959

Author(s):

Ahmed Yassin Bahgat

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Controlled Trial ◽

Tongue Base ◽

Control Group ◽

University Hospitals ◽

Energy Field ◽

Obstructive Sleep ◽

Prospective Randomized Controlled Trial ◽

Significant Difference

Objective Plasma is formed by creating a high-density energy field within an electrically conductive fluid such as saline. Sometimes ablated bits of tissue get stuck between the electrodes of the wand, obstructing the suction channel. The purpose of this study is to investigate the effect of cooling the irrigating saline during ablation of the hypertrophied tongue base in patients with obstructive sleep apnea. Study Design Prospective randomized controlled trial. Setting An otorhinolaryngology department in Main University hospitals. Methods Sixty adult patients with obstructive sleep apnea and tongue base hypertrophy underwent tongue base ablation surgery. Patients were randomly divided into 2 groups of 30 patients each: cooled saline and room temperature saline. The Coblation wand used was the EVac 70 Xtra HP (Smith & Nephew). Results In this study, a significant difference in operative time (mean ± SD) was seen between groups: 21.2 ± 5.5 minutes in the cold group and 47 ± 9.5 minutes in the control group ( P = .001). The wands in the cold group did not obstruct, while all the wands in the control group were obstructed by tissue clogs with variable degrees, hence wasting more time to clean the wands’ tips. Conclusion Cooling the irrigating saline overcame the problem of wand clogs, and the wand tip did not occlude at all during the procedures, thus saving time lost in wand cleaning and demonstrating a faster and safer surgical procedure. Further studies are needed to identify the hemostatic effect of the cooled saline over the regular one.

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Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.716916 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinmei Luo ◽

Xiaona Wang ◽

Zijian Guo ◽

Yi Xiao ◽

Wenhao Cao ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Arterial Stiffness ◽

Endothelial Function ◽

Augmentation Index ◽

Reactive Hyperemia ◽

Control Group ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Tnf Α

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications.Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups.Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = −0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052).Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

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Clinical and Polysomnographic Characteristics of Patients with Extreme Obstructive Sleep Apnea, AHI > 100: A Case-Control Study

Shiraz E-Medical Journal ◽

10.5812/semj.109587 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Forogh Soltaninejad ◽

Negarsadat Neshat ◽

Mehrzad Salmasi ◽

Babak Amra

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Study Results ◽

Significant Difference ◽

Severe Manifestation ◽

The Mean ◽

Nocturnal Polysomnography ◽

Control Study

Background: Severe obstructive sleep apnea (OSA), defined by apnea-hypopnea index (AHI) as more than 30 events per hour, was previously related to more comorbidity. However, limited studies separated the patients with AHI > 100 from those with a less severe manifestation of the disease. Objectives: The current study aimed at describing the characteristics of this subgroup and comparing them with less severe conditions. Methods: A retrospective analysis was conducted on 114 patients with OSA. Nocturnal polysomnography was used to diagnose severe OSA. Patients were categorized into two groups: (1) 60 < AHI < 100 (very severe OSA), (2) AHI ≥ 100 (extreme OSA). Demographic, medical history, and polysomnographic variables were evaluated and compared between the two groups. Results: Extreme OSA was diagnosed in 19 patients, the mean body mass index (BMI) was significantly higher in this group (39.26 ± 5.93 vs. 35.68 ± 6.45 kg/m2, P = 0.025). They also had lower minimal O2 saturation (65.68 ± 10.16 vs. 74.10 ± 8.74, P = 0.003) and more time with < 90% O2 saturation (T < 90%) (81.78 ± 22.57 vs. 58.87 ± 33.14, P = 0.01). OHS prevalence was significantly higher in the group with extreme OSA (P = 0.04). The most frequent comorbidity was hypertension, with an incidence of 60.5%, for the extreme group, although there was no significant difference between the two groups in terms of clinical associations. Conclusions: The current study results suggested that greater BMI and lower minimal O2 saturation, as well as increased T < 90%, were associated with extreme OSA, although no differences were observed in the associated diseases between the compared groups.

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Relationship between HIF-1 and Circadian Clock Proteins in Obstructive Sleep Apnea Patients—Preliminary Study

Journal of Clinical Medicine ◽

10.3390/jcm9051599 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1599 ◽

Cited By ~ 4

Author(s):

Agata Gabryelska ◽

Marcin Sochal ◽

Szymon Turkiewicz ◽

Piotr Białasiewicz

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Circadian Clock ◽

Protein Level ◽

Hypoxia Inducible Factor ◽

Apnea Hypopnea Index ◽

Clock Proteins ◽

Obstructive Sleep ◽

Healthy Control ◽

Circadian Clock Proteins

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and associated with the disruption of circadian rhythm. The study aimed to assess the relationship between hypoxia-inducible factor (HIF) subunits, circadian clock proteins, and polysomnography (PSG) variables, in healthy individuals and severe OSA patients. The study included 20 individuals, who underwent PSG and were divided into severe OSA group (n = 10; AHI ≥ 30) and healthy control (n = 10; AHI < 5) based on apnea-hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. HIF-1α, HIF-1β, BMAL1, CLOCK, CRY1, and PER1 protein concertation measurements were performed using ELISA. In a multivariate general linear model with the concentration of all circadian clock proteins as dependent variables, evening HIF-1α protein level was the only significant covariant (p = 0.025). Corrected models were significant for morning and evening PER1 (p = 0.008 and p = 0.006, respectively), evening (p = 0.043), and evening BMAL protein level (p = 0.046). In corrected models, evening HIF-1α protein level had an influence only on the evening PER1 protein level. Results suggest that OSA patients are at risk for developing circadian clock disruption. This process might be mediated by subunit α of HIF-1, as its increased protein level is associated with overexpression of circadian clock proteins.

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Severity of obstructive sleep apnea (OSA) in 382 Han and Uyghur patients with sleep disorders

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900018500106 ◽

2018 ◽

Vol 01 (02) ◽

pp. 163-169

Author(s):

Aman Gul ◽

Nassirhadjy Memtily ◽

Aikeranmu Aihemaiti ◽

Amir Abdukadir ◽

Palidan Wushuer

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Race And Ethnicity ◽

Impact Factors ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Significant Difference ◽

Adults And Children ◽

Respiratory Disturbance ◽

Distinctive Difference

Objective: Race and ethnicity may impact the prevalence and severity of Obstructive Sleep Apnea (OSA) in adults and children. In this study, we aim to investigate the ethnologic influence on OSA severity between Han and Uyghur OSA patients in Xinjiang, China.Methods: We enrolled total of 382 (205 Han and 177 Uyghur) patients diagnosed with OSA with apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) [Formula: see text] 5. During admission, the severity of OSA was evaluated by polysomnography (PSG).Results: From demographic characteristics of enrolled patients, we found that there was no significant difference in sex, age, BMI, and neck circumference between two study populations. Uyghur OSA patients had longer sleep latency, longer REM sleep and N3 stage, but shorter N1 phase than Han OSA patients. AHI and apnea RDI level, but not hypopnea RDI, were evidently higher in Han patients compared with Uyghur patients. There was no distinctive difference between two ethnic populations in average and minimum peripheral capillary oxygen saturation (SaO2) level.Conclusion: Better understanding of impact factors encompassing ethnicity may help improve OSA diagnosis accuracy, management and treatment for patients in Xinjiang.

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Blood pressure profiles in patients with arterial hypertension and obstructive sleep apnea in different age groups

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2021-27-5-530-535 ◽

2021 ◽

Vol 27 (5) ◽

pp. 530-535

Author(s):

A. N. Kuchmin ◽

V. V. Ekimov ◽

D. A. Galaktionov ◽

I. M. Borisov ◽

A. A. Sheveliov ◽

...

Keyword(s):

Blood Pressure ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Age Groups ◽

Pressure Profile ◽

Control Group ◽

Apnea Hypopnea Index ◽

Blood Pressure Profile ◽

Pressure Profiles ◽

Obstructive Sleep

Background. Obstructive sleep apnea (OSA) is frequently associated with hypertension (HTN), and about 50 % hypertensive patients have concomitant OSA. Episodes of transient upper airway obstruction affect the daily blood pressure profile, leading to nocturnal HTN. Although the general relationship between OSA and the daily blood pressure profile is known, the association between the frequency of various daily blood pressure profiles and OSA severity as well as the age-specific differences remain unknown. The aim of the study was to determine the daily blood pressure profiles in patients with HTN and OSA, depending on the OSA severity and age. Design and methods. The study included 236 HTN patients underwent treatment in the period from 2008 to 2021 years and were diagnosed with OSA by cardiorespiratory monitoring: 84 patients had mild OSA (apnea/hypopnea index (AHI) < 15 episodes/h), 46 patients — moderate OSA (15 ≤ AHI < 30 episodes/h), and 106 patients — severe OSA (AHI ≥ 30 episodes/h). The control group included 140 HTN patients without OSA. Both groups were divided into 3 age subgroups: younger than 45 years, 45–59 years and ≥ 60 years. At baseline, all patients underwent cardiorespiratory monitoring (“Kardiotekhnika‑07–3/12P”, Inkart, St Petersburg, Russia) and 24-hour blood pressure (BP) monitoring (BPLab, Nizhny Novgorod, Russia). Results. We found an association between the distribution of daily BP profiles and age, which differs from that in HTN patients without OSA. Non-dipper and night-peaker BP profiles are predominant in young and middle age. Among OSA patients, the severity of OSA was associated with the BP profiles only in the young and middleage groups. Unfavorable BP profiles (non-dipper and night-peaker) were more common in patients with severe OSA, which was not observed in elderly subgroup. In the elderly, compared to younger patients, the overdipper profile was the most common and its frequency was not associated with OSA severity. Conclusions. The study shows the relationship between the age of patients with HTN and OSA, the OSA severity and the distribution of daily BP profiles.

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Do the turbinates play an important role in obstructive sleep apnea syndrome? – Our experience

Romanian Journal of Rhinology ◽

10.1515/rjr-2016-0011 ◽

2016 ◽

Vol 6 (22) ◽

pp. 93-98

Author(s):

Nicoleta Dumitrescu ◽

Raluca Enache ◽

Codrut Sarafoleanu

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Obstructive Sleep Apnea Syndrome ◽

Sleep Apnea Syndrome ◽

Apnea Hypopnea Index ◽

Nasal Airflow ◽

Nasal Surgery ◽

Obstructive Sleep ◽

Significant Difference ◽

Apnea Syndrome

Abstract BACKGROUND. Nasal obstruction may trigger obstructive sleep apnea syndrome (OSAS) and it is considered to be a cofactor in its pathophysiology. However, the relation between cause and effect still remains a matter of debate. MATERIAL AND METHODS. 18 patients diagnosed with chronic hypertrophic rhinitis and obstructive sleep apnea syndrome were included in the present study. All patients underwent nasal surgery as the single treatment for their sleep breathing disorders. Rhinomanometric (total nasal airflow, logReff, logVR) and polygraphic parameters (apnea-hypopnea index - AHI, snore flags index – SFI) were evaluated pre- and 2 months postoperatively. RESULTS. There was a statistically significant difference between the values of the preoperative and postoperative total nasal airflow (p-value<0.0001). In case of AHI, there was a decrease in its value from 31.56 preoperatively to 30.03 postoperatively, but the difference was not statistically significant (p=0.937). The SFI, on the other hand, presented a significant decrease (p=0.05), from a mean value of 93.15 preoperatively to 56.02 after the surgery. The correlation of the total nasal airflow with AHI and SFI, revealed that nasal surgery had an important impact upon snoring characteristics (r=0.24) and less upon OSAS severity (r=0.21). CONCLUSION. The nasal cavity obstruction contributes less to OSAS, but still represents a disorder that needs to be corrected in case of such patients. Turbinates reduction surgery may be applied in the treatment of OSAS and combined with palate and/or tongue surgery.

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