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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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    Diagnostic Value of Galectin-3 in Exacerbations of Chronic Obstructive Pulmonary Disease
    (Mdpi, 2024) Berber, Nurcan Kirici; Atli, Siahmet; Geckil, Ayseguel Altintop; Erdem, Mehmet; Kiran, Tugba Raika; Otlu, Onder; In, Erdal
    Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by acute exacerbations. Systemic inflammation and oxidative stress play an important role in the pathogenesis of COPD. Exacerbations in COPD reduce the quality of life and are associated with rapid disease progression. Galectin-3 is a beta-galactoside-binding lectin of approximately 30 kDa with pro-inflammatory and pro-fibrotic properties. This study aims to analyze the efficacy of serum galectin-3 in predicting exacerbations in COPD patients. Materials and Methods: Baseline demographic and clinical characteristics of all patients were recorded and blood samples were collected. A total of 58 consecutive COPD patients, including 28 patients (19 male and 9 female) with stable COPD and 30 patients (23 male and 7 female) with acute exacerbation of COPD (AECOPD), were included in the study. Results: Serum galectin-3 levels were significantly higher in the AECOPD group compared to the stable COPD group. A logistic regression analysis revealed that increased galectin-3 levels and disease duration were independent predictors of COPD exacerbation (OR = 5.322, 95% CI: 1.178-24.052, p = 0.03; and OR = 1.297, 95% CI: 1.028-1.635, p = 0.028; respectively). Conclusions: The results of our study demonstrated that Galectin-3 was a strong and independent predictor of exacerbations in COPD patients.
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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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    Evaluation of Oxidative Stress and Endothelial Dysfunction in COVID-19 Patients
    (Mdpi, 2024) Berber, Nurcan Kirici; Kurt, Osman; Geckil, Ayseguel Altintop; Erdem, Mehmet; Kiran, Tugba Raika; Otlu, Onder; In, Erdal
    Background and Objectives: Heat shock proteins (HSPs) are stress proteins. The endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethyl arginine (ADMA) is a mediator of endothelial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes endothelial dysfunction and coagulopathy through severe inflammation and oxidative stress. Using these markers, we analyzed the prognostic value of serum ADMA and HSP-90 levels for early prediction of severe coronavirus disease (COVID-19) patients. Materials and Methods: A total of 76 COVID-19 patients and 35 healthy control subjects were included in this case-control study. COVID-19 patients were divided into two groups: mild and severe. Results: Serum ADMA and HSP-90 levels were significantly higher in the COVID-19 patients compared to the control subjects (p < 0.001). Additionally, serum ADMA and HSP-90 levels were determined to be higher in a statistically significant way in severe COVID-19 compared to mild COVID-19 (p < 0.001). Univariable logistic regression analysis revealed that ADMA and HSP-90, respectively, were independent predictors of severe disease in COVID-19 patients (ADMA (OR = 1.099, 95% CI = 1.048-1.152, p < 0.001) and HSP-90 (OR = 5.296, 95% CI = 1.719-16.316, p = 0.004)). When the cut-off value for ADMA was determined as 208.94 for the prediction of the severity of COVID-19 patients, the sensitivity was 72.9% and the specificity was 100% (AUC = 0.938, 95%CI = 0.858-0.981, p < 0.001). When the cut-off value for HSP-90 was determined as 12.68 for the prediction of the severity of COVID-19 patients, the sensitivity was 88.1% and the specificity was 100% (AUC = 0.975, 95% CI= 0.910-0.997, p < 0.001). Conclusions: Increased levels of Heat shock proteins-90 (HSP-90) and ADMA were positively correlated with increased endothelial damage in COVID-19 patients, suggesting that treatments focused on preventing and improving endothelial dysfunction could significantly improve the outcomes and reduce the mortality rate of COVID-19. ADMA and HSP-90 might be simple, useful, and prognostic biomarkers that can be utilized to predict patients who are at high risk of severe disease due to COVID-19.
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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.
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    Using artificial intelligence to improve the diagnostic efficiency of pulmonologists in differentiating COVID-19 pneumonia from community-acquired pneumonia
    (Wiley, 2022) In, Erdal; Geckil, Aysegul A.; Kavuran, Gurkan; Sahin, Mahmut; Berber, Nurcan K.; Kuluozturk, Mutlu
    Coronavirus disease 2019 (COVID-19) has quickly turned into a global health problem. Computed tomography (CT) findings of COVID-19 pneumonia and community-acquired pneumonia (CAP) may be similar. Artificial intelligence (AI) is a popular topic among medical imaging techniques and has caused significant developments in diagnostic techniques. This retrospective study aims to analyze the contribution of AI to the diagnostic performance of pulmonologists in distinguishing COVID-19 pneumonia from CAP using CT scans. A deep learning-based AI model was created to be utilized in the detection of COVID-19, which extracted visual data from volumetric CT scans. The final data set covered a total of 2496 scans (887 patients), which included 1428 (57.2%) from the COVID-19 group and 1068 (42.8%) from the CAP group. CT slices were classified into training, validation, and test datasets in an 8:1:1. The independent test data set was analyzed by comparing the performance of four pulmonologists in differentiating COVID-19 pneumonia both with and without the help of the AI. The accuracy, sensitivity, and specificity values of the proposed AI model for determining COVID-19 in the independent test data set were 93.2%, 85.8%, and 99.3%, respectively, with the area under the receiver operating characteristic curve of 0.984. With the assistance of the AI, the pulmonologists accomplished a higher mean accuracy (88.9% vs. 79.9%, p < 0.001), sensitivity (79.1% vs. 70%, p < 0.001), and specificity (96.5% vs. 87.5%, p < 0.001). AI support significantly increases the diagnostic efficiency of pulmonologists in the diagnosis of COVID-19 via CT. Studies in the future should focus on real-time applications of AI to fight the COVID-19 infection.