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    Carbonic Anhydrase IX as a Marker of Disease Severity in Obstructive Sleep Apnea
    (Mdpi, 2022) Geckil, Aysegul Altintop; Kiran, Tugba Raika; Berber, Nurcan Kirici; Otlu, Onder; Erdem, Mehmet; In, Erdal
    Background and Objectives: Carbonic anhydrase (CA) enzymes are a family of metalloenzymes that contain a zinc ion in their active sites. CA enzymes have been implied in important situations such as CO2 transport, pH regulation, and oncogenesis. CA-IX is a transmembrane glycoprotein and stimulates the expression of hypoxia-inducible factor-1 (HIF-1) CA-IX. This study aimed to determine serum CA-IX levels in OSA patients in whom intermittent hypoxia is important and to investigate the relationship between serum CA-IX levels and disease severity. Materials and Methods: The study included 88 people who applied to Malatya Turgut Ozal University Training and Research Hospital Sleep Disorders Center without a history of respiratory disease, malignancy, and smoking. Patients were divided into three groups: control (AHI < 5, n = 31), mild-moderate OSA (AHI = 5-30, n = 27) and severe OSA (AHI > 30, n = 30). The analysis of the data included in the research was carried out with the SPSS (IBM Statistics 25, NY, USA). The Shapiro-Wilk Test was used to check whether the data included in the study had a normal distribution. Comparisons were made with ANOVA in multivariate groups and the t-test in bivariate groups. ANCOVA was applied to determine the effect of the CA-IX parameter for OSA by controlling the effect of independent variables. The differentiation in CA-IX and OSA groups was analyzed regardless of BMI, age, gender, and laboratory variables. ROC analysis was applied to determine the parameter cut-off point. Sensitivity, specificity, and cut-off were calculated, and the area under the curve (AUC) value was calculated. Results: Serum CA-IX levels were 126.3 +/- 24.5 pg/mL in the control group, 184.6 +/- 59.1 pg/mL in the mild-moderate OSA group, and 332.0 +/- 39.7 pg/mL in the severe OSA group. Serum CA-IX levels were found to be higher in the severe OSA group compared to the mild-moderate OSA group and control group and higher in the mild-moderate OSA group compared to the control group (p < 0.001, p < 0.001, p < 0.001, respectively). In addition, a negative correlation between CA-IX and minimum SaO(2) and mean SaOI(2) (r = -0.371, p = 0.004; r = -0.319, p = 0.017, respectively). A positive correlation between CA-IX and desaturation index (CT90) was found (r = 0.369, p = 0.005). A positive correlation was found between CA-IX and CRP (r = 0.340, p = 0.010). When evaluated by ROC curve analysis, the area under the curve (AUC) value was determined as 0.940 (95% CI 0.322-0.557; p < 0.001). When the cut-off value for CA-IX was taken as 254.5 pg/mL, it was found to have 96.7% sensitivity and 94.8% specificity in demonstrating severe OSA. Conclusions: Our study found that serum CA-IX value was higher in OSA patients than in control patients, and this elevation was associated with hypoxemia and inflammation. CA-IX value can be a fast, precise, and useful biomarker to predict OSA.
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    Efficacy of serum apelin and galectin-3 as potential predictors of mortality in severe COVID-19 patients
    (Wiley, 2023) Berber, Nurcan Kirici; Geckil, Aysegul Altintop; Altan, Nazife Ozge; Kiran, Tugba Raika; Otlu, Onder; Erdem, Mehmet; In, Erdal
    Apelin is a cardioprotective biomarker while galectin-3 is a pro-inflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in Coronavirus disease 2019 (COVID-19) infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia. The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into two groups, survivors and nonsurvivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected, and blood samples were taken before treatment. In our study, serum apelin levels were determined to be significantly lower in both nonsurvivor and survivor COVID-19 patients compared to the control subjects (for both groups, p < 0.001). However, serum apelin levels were similar in survivor and nonsurvivor COVID-19 patients (p > 0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in nonsurvivors compared to survivors and controls (for both groups; p < 0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p < 0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r = 0.32, p = 0.004; r = 0.24, p = 0.04; r = 0.24, p = 0.03; and r = 0.33, p = 0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r = -0.31, p = 0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID-19 patients (odds ratio [OR] = 2.272, 95% confidence interval [CI] = 1.106-4.667; p = 0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/ml, it was discovered to predict mortality with 80% sensitivity and 57% specificity (area under the curve = 0.738, 95% CI = 0.611-0.866, p = 0.002). Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients.
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    Impact of rem-related obstructive sleep apnea therapy on anxiety, depression and daytime sleepiness
    (Bayrakol Medical Publisher, 2022) Geckil, Aysegul Altintop; Ermis, Hilal
    Aim: Obstructive Sleep Apnea (OSA) is characterized by repetitive episodes of complete or partial upper airway obstruction during sleep. Patients who slept at least 30 minutes in REM sleep, total apnea-hypopnea index (AHI)>5 and REM AHI/NREM AHI>2 are defined as REM-related OSA. We investigated the efficacy of treatment on anxiety, depression and daytime sleepiness in REM-related OSA. Material and Methods: A total of 110 patients with REM-related OSA participated in the study. Patients were divided into two groups; the treatment group consisted of patients who received treatment (n:38) and the non-treatment group who refused to receive treatments (n:72). Of the 38 patients treated, 33 had mild disease and 5 had moderate disease. Sixty-seven of the 72 patients who did not receive treatment had mild disease and 5 had moderate disease. Both groups completed the HADS (Hospital Anxiety-Depression Scale), ESS (Epworth Sleepiness Scale) questionnaires. SPSS was used for data analysis. Results were expressed as mean and standard deviation. T-test and chi-square tests were performed to compare cases. A p-value <0.05 was considered statistically significant. Results: There was no statistically significant difference between the groups, in terms of age, gender, height, weight, and body mass index (BMI). No statistically significant difference was found between the two groups in terms of polysomnography parameters AHI, REM AHI, arousal index, periodic leg movement (PLM) index, sleep latency, REM latency, minimum oxygen saturation (SPO2), and cumulative percentage of time spent at saturation below 90%. HADS- Anxiety, HADS- Depression and ESS scores were significantly higher in the non-treatment group in comparison to the treatment group (p=0.011, p=0.016, p=0.005, respectively). Discussion: The results of our study showed that treatment has positive effects on anxiety, depression and daytime sleepiness, which are indicative of the quality of life in patients with REM-related OSA.
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    Is There a Relationship between Voice Quality and Obstructive Sleep Apnea Severity and Cumulative Percentage of Time Spent at Saturations below Ninety Percent: Voice Analysis in Obstructive Sleep Apnea Patients
    (Mdpi, 2022) Yaslikaya, Serhat; Geckil, Aysegul Altintop; Birisik, Zehra
    Background and Objectives: Apnea hypopnea index is the most important criterion in determining the severity of obstructive sleep apnea (OSA), while the percentage of the total number of times which oxygen saturation is measured below 90% during polysomnography (CT90%) is important in determining the severity of hypoxemia. As hypoxemia increases, inflammation will also increase in OSA. Inflammation in the respiratory tract may affect phonation. We aimed to determine the effects of the degree of OSA and CT90% on phonation. Materials and Methods: The patients were between the ages of 18-60 years and were divided into four groups: normal, mild, moderate, and severe OSA. Patients were asked to say the vowels /alpha:/ and /i:/ for 5 s for voice recording. Maximum phonation time (MPT) was recorded. Using the Praat voice analysis program, Jitter%, Shimmer%, harmonics-to-noise ratio (HNR), and f0 values were obtained. Results: Seventy-two patients were included. Vowel sound /alpha:/; there was a significant difference for Jitter%, Shimmer%, and HNR measurements between the 1st and the 4th group (p < 0.001, p < 0.001, and p < 0.001, respectively) and a correlation between CT90% and Shimmer% and HNR values (p < 0.001 and p < 0.021, respectively). Vowel sound /i:/; there was a significant difference in f0 values between the 1st group and 2nd and 4th groups (p < 0.028 and p < 0.015, respectively), and for Jitter%, Shimmer%, and HNR measurements between the 1st and 4th group (p < 0.04, p < 0.000, and p < 0.000, respectively), and a correlation between CT90% and Shimmer% and HNR values (p < 0.016 and p < 0.003, respectively). The difference was significant in MPT between the 1st group and 3rd and 4th groups (p < 0.03 and p < 0.003, respectively). Conclusions: Glottic phonation can be affected, especially in patients whose AHI scores are >= 15. Voice quality can decrease as the degree of OSA increases. The increase in CT90% can be associated with the worsening of voice and can be used as a predictor in the evaluation of voice disorders in the future.
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    Oxygen regulated protein 150 can be considered as a severity indicator in obstructive sleep apnea
    (Nature Portfolio, 2025) Otlu, Onder; Erdem, Mehmet; Kiran, Tugba Raika; Inceoglu, Feyza; Geckil, Aysegul Altintop; Berber, Nurcan Kirici; In, Erdal
    Oxygen-regulated protein 150 (ORP150) is a chaperone found in the endoplasmic reticulum (ER) induced by ER stress, oxidative stress, glutamate toxicity, ischemia, and hypoxia. Increased expression of ORP150 protects the cells by stopping ER stress, maintaining calcium balance, and delaying apoptosis. In this study, we aim to investigate serum ORP150 amount in patients with different severity levels of obstructive sleep apnea (OSA). Forty-nine patients (25 of severe and 24 of mild-moderate), and 23 healthy controls were included in the study. Routine biochemical measurements and serum ORP150 measurements of all groups and sleep quality measurements of OSA groups were obtained. ELISA was used to measure ORP150 levels in serum samples. In addition, ROC analysis was performed to determine the diagnostic power of the ORP150 parameter. There are significant differences between all three groups in terms of ORP150 values (severe OSA: 8.03 +/- 0.4 ng/mL; mild-moderate OSA: 5.54 +/- 0.47 ng/mL; control: 4.41 +/- 0.25 ng/mL, p < 0.017). The highest ORP150 level belongs to the severe OSA group and there is a direct correlation between the severity of the disease and ORP150 levels. ORP150 value is a distinguishing parameter for OSA and the cut-off value of ORP150 was observed as 7.14 ng/mL. We concluded that serum ORP150 levels can be a differential diagnostic parameter in OSA patients and that disease severity can be determined by serum ORP150 measurement.
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    The effects of disease severity and comorbidity on oxidative stress biomarkers in obstructive sleep apnea
    (Springer Heidelberg, 2024) Kiran, Tugba Raika; Otlu, Onder; Erdem, Mehmet; Geckil, Aysegul Altintop; Berber, Nurcan Kirici; In, Erdal
    PurposeIschemia-modified albumin (IMA), total oxidant status (TOS), and total antioxidant status (TAS) are biomarkers used to evaluate oxidative stress status in various diseases including obstructive sleep apnea (OSA). In this study, we investigated the effects of disease severity and comorbidity on IMA, TOS and TAS levels in OSA.MethodsPatients with severe OSA (no-comorbidity, one comorbidity, and multiple comorbidities) and mild-moderate OSA (no-comorbidity, one and multiple comorbidities), and healthy controls were included in the study. Polysomnography was applied to all cases and blood samples were taken from each participant at the same time of day. ELISA was used to measure IMA levels in serum samples and colorimetric commercial kits were used to perform TOS and TAS analyses. In addition, routine biochemical analyses were performed on all serum samples.ResultsA total of 74 patients and 14 healthy controls were enrolled. There was no statistically significant difference between the disease groups according to gender, smoking status, age, body mass index (BMI), HDL, T3, T4, TSH, and B12 (p > 0.05). As the severity of OSA and comorbidities increased, IMA, TOS, apnea-hypopnea index (AHI), desaturation index (T90), cholesterol, LDL, triglyceride, AST, and CRP values increased significantly (p < 0.05). On the other hand, TAS, minimum desaturation, and mean desaturation values decreased significantly (p < 0.05).ConclusionsWe concluded that IMA, TOS, and TAS levels may indicate OSA-related oxidative stress, but as the severity of OSA increases and with the presence of comorbidity, IMA and TOS levels may increase and TAS levels decrease. These findings suggest that disease severity and presence/absence of comorbidity should be considered in studies on OSA.