Evaluation Of Oxidative Stress Parameters In Asthmatic Children: A Case-Control Study

Evaluation Of Oxidative Stress Parameters In Asthmatic Children: A Case-Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation Of Oxidative Stress Parameters In Asthmatic Children: A Case-Control Study Hacer Efnan Melek Arsoy, Bahri ELMAS, Öner ÖZDEMİR, Hayrullah YAZAR, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6077681/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background To compare some oxidative stress parameters between pediatric asthmatic individuals and healthy children, and to investigate the relationship between pediatric asthma severity and control status with oxidative stress. Methods This case-control study was performed between June–December 2016, including children with asthma and healthy controls. Asthmatic patients were classified according to severity and disease-control status. Asthmatic children and controls were compared in terms of native thiol, total thiol, disulfide levels, disulfide/native thiol ratio, disulfide/total thiol ratio, native thiol/total thiol ratio, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI). Patients classified according to asthma severity and control status were also analyzed in terms of these parameters. Results A total of 102 subjects, consisting of 60 asthmatic children (asthma group), and 42 non-asthmatic children (the control group), were included in the study. There was no significant difference between the asthma and control groups in terms of age (p = 0.080) and sex distribution (p = 0.178). In the asthma group, mean native thiol (p < 0.001), total thiol (p < 0.001), disulfide (p < 0.001) levels, TOS (p = 0.001) and TAC (p = 0.050) values, disulfide/native thiol (p = 0. 001) and disulfide/total thiol (p = 0.002) ratios were significantly higher and native thiol/total thiol ratio was significantly lower (p = 0.002) than the control group. Native thiol, total thiol, and disulfide levels had the best discriminatory ability to detect asthma. Multivariable logistic regression identified native thiol and total thiol as being independently associated asthma presence. Conclusion Oxidative stress appears to be associated with the pathophysiology of pediatric asthma, but more studies are needed to confirm the relationship between oxidative stress and asthma severity and control status. Child asthma oxidative stress oxidants antioxidants disulfides Figures Figure 1 1. INTRODUCTION Bronchial asthma, the most prevalent chronic respiratory condition among children and continues to rise in prevalence, particularly in developing nations [1, 2]. Asthma is characterized by persistent inflammation and and airway structural changes, asthma is widely recognized as a chronic inflammatory disease despite gaps in understanding its exact pathological origins [3, 4]. Oxidative stress, a critical factor in aging and various pathologies, results from an imbalance between pro-oxidants like reactive oxygen species (ROS) and reactive nitrogen species (RNS), and antioxidant defenses such as enzymatic (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (glutathione, vitamins C, E, and A, bilirubin) [1, 5, 6] [7, 8]. Studies reveal a strong association between asthma severity and elevated oxidative stress, with ROS contributing to progressive airway deterioration[1, 9]. Thiol groups in cellular proteins, containing sulfhydryl groups, protect against oxidative damage by forming disulfide bonds through oxidation, which are subsequently reduced to regenerate thiols. This cycle maintains a dynamic thiol/disulfide homeostasis crucial for antioxidant defense, detoxification, cell signaling, apoptosis, and enzymatic regulation [10] [11] [12] [13]. Recently, thiol/disulfide homeostasis has emerged as a novel oxidative stress marker in diseases like asthma [14, 15]. Limited data exist on oxidant-antioxidant status, particularly dynamic thiol/disulfide homeostasis, in pediatric asthma patients. These compounds may influence etiopathogenesis, disease severity, and control in pediatric asthma. This study aims to evaluate oxidant and antioxidant markers, including thiol/disulfide parameters, in asthmatic children and healthy controls, and investigate the relationship between oxidative stress, asthma severity, and disease control. 2. MATERIALS AND METHODS 2.1. Data collection steps and tools This case-control study was conducted in the Pediatric Immunology and Allergy Department of xxx University Research and Training Hospital (June–December 2016). The patient group included children aged 6–17 years diagnosed with asthma, while the control group comprised age- and sex-matched healthy children referred for routine pre-operative evaluations. Participants were from non-smoking households, and exclusions included children under six, those with transient wheeze, comorbidities, recent infections, or using medications influencing oxidative status. 2.2. Data collection steps and tools The age and sex data of all participants were recorded. In the asthma group, data on asthma duration, lung function tests, attack frequency, daytime symptoms, rescue treatment needs, and medications used were also collected 2.2.1. Asthma diagnosis and classification The Global Initiative for Asthma (GINA) 2014 guidelines [16] were used in asthma diagnosis and classification. [17]. Patients were classified with GINA criteria as uncontrolled, partially-controlled, and controlled. Severity of asthma was determined using clinical signs and changes in spirometry values. 2.2.2. Laboratory analysis All laboratory measurements were conducted in certified biochemistry laboratories using calibrated devices per manufacturer instructions. Peripheral venous blood (5 mL) was collected from asthmatic children upon admission and from healthy controls during routine visits. After centrifugation at 1500 rpm for 10 minutes, serum samples were stored at − 80°C until analysis. Thiol/disulfide status was assessed using the Erel and Neselioglu method [18], reducing disulfide bonds to free thiols, followed by neutralization with formaldehyde. Thiol levels were measured with DTNB, and disulfide levels were calculated as half the difference between total and native thiols. Ratios for disulfide/native thiol, disulfide/total thiol, and native/total thiol were determined with an automated analyzer (Cobas 501; Roche Diagnostics). Laboratory staff were blinded to patient data. Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured using Rel Assay Diagnostics kits on an automated analyzer (Architect C16000; Abbott Laboratories). TAC was expressed as mmol Trolox equivalent/L, TOS as µmol H2O2 equivalent/L, and oxidative stress index (OSI) was calculated as OSI = (TOS/TAC) × 100 after converting TAC to µmol/L [19]. 2.3. Outcomes The primary outcome was comparing oxidative stress parameters between asthmatic and non-asthmatic children. Secondary outcomes included exploring the relationships between asthma severity, asthma control status, and oxidative stress parameters. 2.4. Statistical analysis Descriptive statistics summarized participant characteristics. The Kolmogorov-Smirnov and Shapiro-Wilk tests assessed numerical variable distributions. Student’s t-test, the Mann-Whitney U test, analysis of variance (ANOVA), and the Kruskal-Wallis 𝐻-test were used as appropriate to compare data between groups. Categorical variables were compared using the chi-squared or Fisher’s exact chi-squared test. Receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of thiol/disulfide parameters for asthma prediction. Step-wise multivariable logistic regression identified independent asthma risk predictors. Statistical analyses were performed with IBM SPSS Statistics (Version 20.0; IBM Corp., 2011), and p < 0.05 was deemed statistically significant. 3. RESULTS A total of 102 subjects, consisting of 60 asthmatic children (asthma group), and 42 healthy controls, were included in the study. The mean age of the control group was 12.66 (2.35) years and the male-to-female ratio was 28/32. The mean age of the asthma group was 11.77 (2.56) years, and the male-to-female ratio was 14/28. There was no significant difference between the groups in terms of age (p = 0.080) or sex distribution (p = 0.178). In the asthma group, mean native thiol (p < 0.001), total thiol (p < 0.001), disulfide (p < 0.001) levels, TOS (p = 0.001) and TAC (p = 0.050) values, disulfide/native thiol (p = 0. 001) and disulfide/total thiol (p = 0.002) ratios were significantly higher, while native thiol/total thiol ratio was significantly lower (p = 0.002) than the control group (Table 1 ). Table 1 Comparison of control and asthma groups in terms of demographic data, biochemical and oxidative stress parameters Control (n = 42) Asthma (n = 60) p value Age 12.66 (2.35) 11.77 (2.56) 0.080 Sex, Male/Female 28/32 14/28 0.178 Native Thiol (µmol/L) 404.719 (53.258) 460.860 (50.723) < 0.001 Total Thiol (µmol/L) 440.764 (54.522) 509.698 (56.381) < 0.001 Disulfide (µmol/L) 18.022 (3.016) 24.419 (7.046) < 0.001 Disulfide/Native Thiol (%) 4.517 (0.944) 5.316 (1.512) 0.001 Disulfide/Total Thiol (%) 4.129 (0.776) 4.772 (1.218) 0.002 Native Thiol/Total Thiol (%) 91.74 (1.553) 90.455 (2.437) 0.002 TOS (mmol/L) 100.050 (20.501) 118.050 (30.855) 0.001 TAC (mmol/L) 1.494 (0.218) 1.590 (0.254) 0.050 OSI ([TOS/TAC] x 100) 6.898 (1.833) 7.593 (2.27) 0.104 Values were represented as frequency, mean (SD), median (min-max). P-values < 0.05 were considered to indicate statistical significance. Student t test, Mann-Whitney U, X^2 Abbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status Thiol and disulfide values/ratios, as well as TOS, were found to have significant discriminatory capacity in detecting asthmatic patients. Among these, native thiol with a cut-off value of 415.1 [AUC (95% CI):0.775 (0.684–0.867); p < 0.001; sensitivity: 81.7%; specificity: 61.9%], total thiol with a cut-off value of 449.35 [AUC (95% CI): 0.808 (0.725–0.892); p < 0.001; sensitivity: 85%; specificity: 61.9%], disulfide with a cut-off value of 21.875 [AUC (95% CI): 0.816 (0.729–0.903); p < 0.001; sensitivity: 66.7%; specificity: 97.6%], were found to have the most notable ROC results (Table 2 , Fig. 1 ). Table 2 Receiver operator curve evaluating thiol disulfide homeostasis parameters and TOS thresholds for asthma AUC (95% CI) Optimum Cut-off p value Sensitivity Specificity Native Thiol (µmol/L) 0.775 (0.684–0.867) 415.1 < 0.001 0.817 0.619 Total Thiol (µmol/L) 0.808 (0.725–0.892) 449.35 < 0.001 0.85 0.619 Disulfide (µmol/L) 0.816 (0.729–0.903) 21.875 < 0.001 0.667 0.976 Disulfide/Native Thiol (%) 0.689 (0.586–0.793) 5.604 0.001 0.433 0.929 Disulfide/Total Thiol (%) 0.689 (0.586–0.793) 5.039 0.001 0.433 0.929 TOS (mmol/L) 0.645 (0.538–0.751) 117.64 0.013 0.317 0.905 The AUC values of TAC, OSI and Native Thiol / Total Thiol were below 0.6. Abbreviations: AUC: Area Under Curve, CI: Confidence interval, TOS: Total oxidant status Table 3 Regression analysis and independent risk factors predicting asthma. Beta (SE) p value OR 95% CI for OR Lower Upper Native Thiol (µmol/L) (-) 0.074 (0.033) 0.023 0.929 0.871 0.99 Total Thiol (µmol/L) 0.091 (0.032) 0.004 1.095 1.029 1.165 (-)2 likelihood: 82.969, Nagelkerke r2 = 0.564, 𝑝 < 0.001. Native thiol, total thiol, TOS and TAC are included in the stepwise logistic regression model. 𝑝 < 0.05 statistical significance. Abbreviations: CI: Confidence Interval, OR: Odds Ratio, SE: Standard Error Multivariable logistic regression revealed that native thiol (OR: 0.929, 95% CI: 0.871–0.99, p = 0.023) and total thiol (OR: 1.095, 95% CI: 1.029–1.165, p = 0.004) were independently associated with the high risk of asthma. In other words, 1 unit of increase in total thiol level was associated with a 1.095-fold increase in the risk of asthma. On the other hand, 1 unit of increase in native thiol level was associated with lower risk of asthma (0.929-fold). The changes in TOS and TAC values were not found to be independently associated with asthma risk (p > 0.005) ( Tablo 3 ). Finally, no significant difference was found between intermittent, mild and moderate asthmatics in terms of examined laboratory variables (Table 4 ). However, patients with controlled asthma had significantly higher TOS levels than those with partially-controlled disease (p = 0.037). Apart from this, no significant parameter differences were observed between groups divided with respect to disease control status (Table 5 ). Table 4 Laboratory parameters according to severity of asthma. Asthma severity Intermittent (n = 10) Mild (n = 31) Moderate (n = 19) p value Native Thiol (µmol/L) 484.600 (38.780) 455.019 (52.132) 457.895 (52.635) 0.268 Total Thiol (µmol/L) 539.550 (46.758) 500.151 (57.665) 509.563 (55.968) 0.159 Disulfide (µmol/L) 27.475 (5.871) 22.566 (6.296) 25.834 (8.136) 0.089 Disulfide/Native Thiol (%) 5.650 (0.989) 4.968 (1.342) 5.706 (1.889) 0.185 Disulfide/Total Thiol (%) 5.064 (0.788) 4.493 (1.106) 5.074 (1.496) 0.188 Native Thiol/Total Thiol (%) 89.871 (1.575) 91.013 (2.212) 89.851 (2.992) 0.188 TOS (mmol/L) 131.290 (37.761) 111.400 (27.706) 121.930 (30.640) 0.168 TAC (mmol/L) 1.620 (0.246) 1.591 (0.256) 1.572 (0.265) 0.891 OSI ([TOS/TAC] x 100) 8.176 (2.149) 7.185 (2.251) 7.953 (2.350) 0.349 Values were represented as mean (SD), median (min-max). P values of < 0.05 were considered to indicate statistical significance Abbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status Table 5 Laboratory findings according to asthma control status Asthma control level Controlled (n = 9) Partially-Controlled (n = 33) Uncontrolled (n = 18) p value Native Thiol (µmol/L) 468 (65.85) 466.178 (43.701) 447.54 (54.99) 0.417 Total Thiol (µmol/L) 520.44 (75.85) 513.378 (45.478) 497.58 (64.72) 0.530 Disulfide (µmol/L) 26.22 (8.53) 23.600 (5.081) 25.02 (9.274) 0.566 Disulfide/Native Thiol (%) 5.59 (1.6) 5.103 (1.241) 5.567 (1.904) 0.493 Disulfide/Total Thiol (%) 4.994 (1.338) 4.609 (1.0129) 4.960 (1.504) 0.524 Native Thiol/Total Thiol (%) 90.01 (2.676) 90.781 (2.025) 90.078 (3.009) 0.524 TOS (mmol/L) 114.28 (105–196) a 106.27 (71–176) 114.3 (77–180) 0.037 TAC (mmol/L) 1.513 (1.258–1.953) 1.554 (1.054–2.111) 1.529 (1.210–2.099) 0.993 OSI ([TOS/TAC] x 100) 8.412 (5.997–11.782) 6.426 (4.348–11.422) 7.065 (5.353–13.463) 0.096 Values were represented as mean (SD), median (min-max). P-values < 0.05 were considered to indicate statistical significance a : different from partly controlled Abbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status 4. DISCUSSION Asthma is the leading chronic inflammatory lung disease in children, with oxidative stress playing a key role in airway inflammation [13]. This study, aimed at exploring the link between pediatric asthma and oxidative stress, found that native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, TOS, and TAC levels were significantly higher, while native thiol/total thiol was lower in asthmatic children compared to healthy controls. Disulfide emerged as the most distinctive marker for asthma, and elevated native and total thiol levels were identified as independent risk factors for asthma presence. However, no variable was linked to asthma severity. Notably, controlled asthmatic children had significantly lower TOS levels than those with partially controlled disease. Asthma is closely associated with oxidative stress, which contributes to airflow obstruction, airway hyperreactivity, and remodeling. Antioxidants are essential for neutralizing reactive oxygen and nitrogen species (ROS/RNS) generated during normal metabolism, maintaining airway balance. In asthma, elevated ROS/RNS and reduced enzymatic antioxidants result in decreased antioxidant activity, a hallmark of the disease [20]. Thiols, crucial components of the plasma antioxidant system, include albumin, glutathione (GSH), thioredoxin, cysteine, and homocysteine [13]. Assessing thiol/disulfide homeostasis offers insights into oxidative stress, though studies comparing these markers in asthmatic vs. healthy children remain limited. This study found significantly higher levels of native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, TOS, and TAC in asthmatic children, with a lower native thiol/total thiol ratio. ROC analysis identified total thiol > 49.35 as the most sensitive marker and disulfide > 21.875 as the most specific. Native thiol and total thiol were independent risk factors for asthma. In a recent study, children with well-controlled asthma had decreased serum levels of thiol groups, tryptophan, and TAC compared to healthy children, indicating persistent oxidative stress even in controlled asthma [21]. Another study found significantly reduced superoxide dismutases (SOD) and glutathione peroxidases (GPx) activities alongside elevated malondialdehyde (MDA) levels in asthmatic children [22]. Fabian et al. reported lower plasma antioxidant levels, including vitamins A and E, selenium, and coenzyme Q10, and higher MDA levels in asthmatic children compared to controls, along with reduced TAC [23]. A Turkish study revealed that asthmatic children had higher MDA and lower reduced GSH levels, with asthma identified as an independent oxidative stress factor [24]. Celik et al. demonstrated elevated MDA and reduced GSH in nasal and oral exhaled breath samples of asthmatic children [25]. Similarly, a case-control study showed increased serum oxidant markers like asymmetric dimethylarginine and MDA, along with decreased paraoxonase activity in asthmatic children compared to healthy controls [26]. Severe, treatment-resistant asthma in children remains challenging to manage despite high-dose corticosteroids. While mild-to-moderate asthma responds to low-dose inhaled corticosteroids, the underlying mechanisms of severe asthma remain unclear, with excessive free radical generation as a key feature. [27]. Monitoring oxidative stress by-products has been suggested as a potential indicator of asthma severity [28], with studies linking oxidative stress markers to poorer clinical control, increased severity, and reduced lung function [29]. The extent of bronchial hyperreactivity has also been associated with reactive ROS levels [30]. In this study, none of the oxidant or antioxidant parameters were linked to asthma severity. Nar et al. found a positive correlation between forced exhalation volume in one second (FEV1) and forced vital capacity (FVC) with native and total thiol levels, though no correlation with FEV1/FVC or other thiol/disulfide parameters. Disulfide levels correlated positively with positive expiratory pressure [13]. Dilek et al. compared newly diagnosed asthma patients (Group I) and those on montelukast therapy for over 4 months (Group II), finding lower plasma total thiol in Group I, while Group II levels resembled controls. No significant difference in TAS or total thiol was observed between Groups I and II [31]. Anne et al. hypothesized that Nrf2 dysfunction in severe asthma depletes thiol reserves. Their study revealed increased oxidation and reduced GSH and cysteine levels in severe asthma, with impaired Nrf2 function despite elevated Nrf2 expression [27]. Ammar et al. found spirometry correlated with SOD activity but not with MDA, GSH, or GPx [32]. Another study noted a negative correlation between FEV1 (% predicted) and MDA, and a positive correlation with GSH [33]. Dut et al. observed no difference in MDA and GSH levels between mild and moderate asthmatics [24]. A case-control study found higher serum oxidants and lower antioxidants in severe asthma, identifying MDA as a strong predictor of severity [26]. Clusterin, an oxidative stress indicator with antioxidant properties, is elevated in severe asthma and inversely correlates with lung function [34]. Oxidative stress drives asthma development and persistence by inducing excessive ROS/RNS production, particularly during allergen exposure, infections, and pollution. This promotes airway remodeling, reduces treatment response, and worsens clinical outcomes, especially in uncontrolled asthma. [1]. In the present study, children with controlled asthma had significantly lower TOS levels than those with partially controlled asthma, though no difference was found between uncontrolled and other groups. This may be due to the small number of patients. Stephenson et al. linked cysteine oxidation with elevated oxidative stress, reduced glucocorticoid receptor activity, and poorer asthma control. Children with high cysteine oxidation exhibited increased ROS, elevated CCL3 and CXCL1 expression, and diminished glucocorticoid responsiveness [35]. In a prospective study, uncontrolled asthma was associated with elevated MDA, advanced oxidation protein products, increased SOD activity, and decreased GSH and GPx levels [32]. Karadogan et al. found that MDA and protein carbonyl levels were higher in uncontrolled asthma compared to controlled groups, while catalase activity was elevated in partially controlled asthma. TAC was significantly lower in uncontrolled asthma, with a negative correlation between asthma control scores and oxidative stress biomarkers [33]. Fernando et al. reported increased nitric oxide metabolites in asthma patients regardless of control status. TAC levels were lower in poorly controlled asthma but showed no difference between well-controlled patients and healthy controls, suggesting higher TAC may aid asthma control [36]. Some studies propose paraoxonase and TOS as biomarkers for identifying uncontrolled asthma in children [37]. As mentioned above, numerous investigations have highlighted that cells involved in airway inflammation in asthma serve as a significant source of ROS in affected individuals [38]. The oxidative damage inflicted upon biomolecules can yield both functional and structural repercussions, exerting a pivotal influence on the onset, persistence, and outcomes of asthma across all phenotypes or endotypes. Given the fundamental role of inflammation in the pathogenesis of all forms and subtypes of asthma, ROS and RNS, alongside compromised antioxidant defense mechanisms and biomolecular oxidation, give rise to a myriad of consequences. These include heightened release of arachidonic acid from cell membranes and the generation of inflammatory markers, augmented hyperreactivity and contraction of airway smooth muscle, increased vascular permeability leading to airway edema, elevated bronchial hyperresponsiveness and mucus secretion, enhanced synthesis of pro-inflammatory cytokines and chemoattractants, triggered release of tachykinins and neurokinins fostering neurogenic inflammation, and impaired responsiveness to bronchodilators [39]. Moreover, oxidative damage to DNA and histones may induce epigenetic alterations, diminishing the efficacy of anti-asthmatic medications, such as corticosteroids [40]. Our data found increased both oxidant and antioxidant markers in pediatric asthmatic patients independent of disease severity and control status. These results largely contradict the existing literature data. Because in most of the studies whose results are presented above, it is seen that the levels of oxidant parameters increase and the levels of antioxidant parameters decrease in asthma. In addition, it has been shown in many studies that oxidative stress increases in uncontrolled asthma compared to controlled asthma and as the severity of asthma increases. There may be several possible reasons for our results. (i) The increase in both oxidant and antioxidant markers in patients may be the result of a compensatory mechanism against increased oxidative stress. (ii) Differences in the measurement methods of thiol/disulfide homeostasis parameters may have led to different results. The measurement method we used is thought to give more reliable results compared to previous measurement methods [1]. However, study designs comparing different measurement methods are necessary to support this hypothesis. (iii) There is a possibility that asthma treatments may affect oxidative stress parameters and that there may be treatment differences between the study populations. Comprehensive studies including treatment details are required. (iv) The number of studies investigating thiol/disulfide homeostasis parameters and their relationship with asthma severity and control status in pediatric asthmatics is very limited. The disulfide level is expected to increase and the thiol level decreases under oxidative stress. But both disulfide levels and thiol levels observed in our study were higher than those in healthy subjects. These findings may be explained by the factors affecting the thiol-disulfide balance except oxidative stress such as the rates of the thiol-disulfide exchange reactions, thiol oxidation by ROS and possible repair processes, enzymatic extracellular degradation of GSH and liver release of thiol-containing molecules. The possible effects of possible pathophysiological differences between pediatric and adult asthma on the results obtained should be investigated in more comprehensive studies. (v) [41]. The different number of participants between the groups may have affected the statistical findings. 5. LIMITATIONS The single-center design of this study limits external validity. The number of participants is relatively small. The different number of subjects between the groups may have had an effect on the statistical analyses. The number of patients with severe asthma was very small, and therefore, these patients were not examined as a separate group. It is also evident that clarifying the mechanistic relationships between oxidative stress and pediatric asthma necessitates longitudinal follow-up of oxidative stress markers. This was not done in the current study. The details about some factors that may have an impact on oxidative stress marker levels were not considered, including nutritional status, environmental factors, duration of asthma, further details of asthma treatment, time of last asthma attack, and attack periodicity. Other parameters of oxidative stress such as SOD, GPx, GSH and MDA were not examined. 6. CONCLUSION Data from the current study reveals that native thiol, total thiol, disulfide, disulfide, disulfide/native thiol, disulfide/total thiol, TOS and TAC were significantly higher and native thiol/total thiol was significantly lower in asthmatic children compared to healthy ones. High disulfide was the most valuable parameter for predicting asthmatic children. High native thiol and total thiol were independent risk factors for asthma. There was no significant association between oxidative stress parameters and asthma severity and control status. Clarification of the relationship between oxidative stress parameters, especially those related to thiol/disulfide homeostasis, and pediatric asthma may allow the development of new treatment regimens to control the onset and severity of the disease and to treat persistent asthma. However, further studies seem to be needed to clarify the pathophysiological links between oxidative stress and the onset, severity and controlling of pediatric asthma. Abbreviations FEV1 Forced exhalation volume in one second FVC Forced vital capacity GSH Glutathione GPx Glutathione peroxidases GINA The Global Initiative for Asthma MDA Malondialdehyde OSI Oxidative stress index ROS Reactive oxygen species RNS Reactive nitrogen species SOD Superoxide dismutases TAC Total antioxidant capacity TOS Total oxidant status Declarations Acknowledgments There is no acknowledgments. Author contributions HEMA and BE are responsible for conceptualizing the study framework, drafting the manuscript, and conducting comprehensive critical revisions. BE performed statistical analyses. BE and ÖÖ actively participated in patient care and clinical data collection, contributing to the interpretation of clinical outcomes. HY, CB, and ÖE developed the data collection strategy and conducted laboratory procedures with detailed validation steps. All authors read and approved the final manuscript. Data availability Datasets is avaible. The patients data is avaible from the correspondng author on reasonable request ( [email protected] ). Disclosure statement / Competing interests No potential conflict of interest was reported by the authors. Manuscript contents are solely the responsibility of the authors. All other authors declare that they have no conflicts of interests. Generative Artificial Intelligence (AI) Disclosure Generative artificial intelligence was not used in any aspect of this study. Funding The authors reported that there is no funding associated with the work featured in this article. Sakarya University, will support publication of the manuscript if accepted. Ethical Considerations and consent for publication There is no Ethical Considerations. The study was initiated after approval by our local (Sakarya University) ethics committee (No: 16214662 / 050.01.04/88) and the study adhered to the Declaration of Helsinki. Informed consent was received from participants (verbal) and their parents (written), following good clinical practice guidelines. All procedures were in accordance with ethical standards and the information in the journal's manual and Declaration of Helsinki and ethical guidelines. Consent to Participate Written informed consent was obtained from the parents or legal guardians of all pediatric participants prior to inclusion in the study. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Clinical trial number Not applicable. References Jesenak, M., M. Zelieskova, and E. Babusikova, Oxidative stress and bronchial asthma in children—causes or consequences? Frontiers in pediatrics, 2017. 5 : p. 162. Anandan, C., et al., Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy, 2010. 65 (2): p. 152 − 67. James, A. and G. Hedlin, Biomarkers for the Phenotyping and Monitoring of Asthma in Children. Curr Treat Options Allergy, 2016. 3 (4): p. 439–452. Nosal, S., et al., Changes of airway obstruction parameters in healthy children caused by mother's smoking during pregnancy. J Physiol Pharmacol, 2008. 59 Suppl 6 : p. 523-9. Yalcinkaya, A., et al., Oxysterol concentrations are associated with cholesterol concentrations and anemia in pediatric patients with sickle cell disease. Scandinavian Journal of Clinical and Laboratory Investigation, 2019. 79 (6): p. 381–387. Yildirim, N., et al., Evaluation of the relationship between intravascular hemolysis and clinical manifestations in sickle cell disease: decreased hemopexin during vaso-occlusive crises and increased inflammation in acute chest syndrome. Annals of Hematology, 2022. 101 (1): p. 35–41. Rhee, S.G. and I.S. Kil, Multiple Functions and Regulation of Mammalian Peroxiredoxins. Annu Rev Biochem, 2017. 86 : p. 749–775. Tsutsui, H., S. Kinugawa, and S. Matsushima, Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol, 2011. 301 (6): p. H2181-90. Babusikova, E., et al., Importance of oxidative damage in the pathogenesis of bronchial asthma in children. Acta Pneumol Allergol Pediatr, 2010. 13 : p. 13 − 7. Thomas, J.A., B. Poland, and R. Honzatko, Protein sulfhydryls and their role in the antioxidant function of protein S-thiolation. Arch Biochem Biophys, 1995. 319 (1): p. 1–9. Cremers, C.M. and U. Jakob, Oxidant sensing by reversible disulfide bond formation. J Biol Chem, 2013. 288 (37): p. 26489-96. Jones, D.P. and Y. Liang, Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med, 2009. 47 (10): p. 1329-38. Nar, R. and A.G. Çalış, Assessment of dynamic thiol/disulfide homeostasis in patients with asthma. Journal of laboratory medicine, 2018. 42 (3): p. 99–104. Ates, I., et al., Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension. J Am Soc Hypertens, 2016. 10 (2): p. 159 − 66. Fidan, F., et al., Dynamic Thiol/Disulphide Homeostasis in Patients With Fibromyalgia. Arch Rheumatol, 2017. 32 (2): p. 112–117. Reddel, H.K. and M.L. Levy, The GINA asthma strategy report: what's new for primary care? NPJ Prim Care Respir Med, 2015. 25 : p. 15050. Behrman, R.E., R.M. Kliegman, and H.B. Jenson, Nelson textbook of pediatrics. 2000. Erel, O. and S. Neselioglu, A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem, 2014. 47 (18): p. 326 − 32. Yumru, M., et al., Oxidative imbalance in bipolar disorder subtypes: a comparative study. Prog Neuropsychopharmacol Biol Psychiatry, 2009. 33 (6): p. 1070-4. Sahiner, U.M., et al., Oxidative stress in asthma: Part of the puzzle. Pediatric Allergy and Immunology, 2018. 29 (8): p. 789–800. Biesiadecki, M., et al., A Comparative Study of Oxidative Stress Biomarker Levels in Asthmatic and Non-Asthmatic Children. Biointerface Res. Appl. Chem, 2022. 13 : p. 280. Shokry, D.M. and S.A. El-Tarahony, Oxidant-antioxidant balance in childhood asthma. Egyptian Journal of Pediatric Allergy and Immunology (The), 2013. 11 (1). Fabian, E., et al., Nutritional supplements and plasma antioxidants in childhood asthma. Wien Klin Wochenschr, 2013. 125 (11–12): p. 309 − 15. Dut, R., et al., Oxidative stress and its determinants in the airways of children with asthma. Allergy, 2008. 63 (12): p. 1605-9. Celik, M., et al., Oxidative stress in the airways of children with asthma and allergic rhinitis. Pediatr Allergy Immunol, 2012. 23 (6): p. 556 − 61. El-Alameey, I.R., et al., Relationship of Oxidant and Antioxidant Markers to Asthma Severity in Egyptian Asthmatic Children. Open Access Maced J Med Sci, 2017. 5 (5): p. 645–650. Fitzpatrick, A.M., et al., Thiol redox disturbances in children with severe asthma are associated with posttranslational modification of the transcription factor nuclear factor (erythroid-derived 2)-like 2. J Allergy Clin Immunol, 2011. 127 (6): p. 1604-11. Jiang, L., et al., Molecular characterization of redox mechanisms in allergic asthma. Ann Allergy Asthma Immunol, 2014. 113 (2): p. 137 − 42. Fatani, S.H., Biomarkers of oxidative stress in acute and chronic bronchial asthma. J Asthma, 2014. 51 (6): p. 578 − 84. Calhoun, W.J., et al., Enhanced superoxide production by alveolar macrophages and air-space cells, airway inflammation, and alveolar macrophage density changes after segmental antigen bronchoprovocation in allergic subjects. Am Rev Respir Dis, 1992. 145 (2 Pt 1): p. 317 − 25. Dilek, F., et al., Plasma total thiol pool in children with asthma: Modulation during montelukast monotherapy. Int J Immunopathol Pharmacol, 2016. 29 (1): p. 84 − 9. Ammar, M., et al., Oxidative stress in patients with asthma and its relation to uncontrolled asthma. J Clin Lab Anal, 2022. 36 (5): p. e24345. Karadogan, B., et al., Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control. J Asthma, 2022. 59 (4): p. 663–672. Kwon, H.S., et al., Clusterin expression level correlates with increased oxidative stress in asthmatics. Ann Allergy Asthma Immunol, 2014. 112 (3): p. 217 − 21. Stephenson, S.T., et al., Cysteine oxidation impairs systemic glucocorticoid responsiveness in children with difficult-to-treat asthma. J Allergy Clin Immunol, 2015. 136 (2): p. 454 − 61.e9. Fernando, Y., et al., Differences in serum markers of oxidative stress in well controlled and poorly controlled asthma in Sri Lankan children: a pilot study. Allergy Asthma Clin Immunol, 2020. 16 : p. 66. Emin, O., A. Hasan, and D.M. Rusen, Plasma paraoxonase, oxidative status level, and their relationship with asthma control test in children with asthma. Allergol Immunopathol (Madr), 2015. 43 (4): p. 346 − 52. Andreadis, A.A., et al., Oxidative and nitrosative events in asthma. Free Radical Biology and Medicine, 2003. 35 (3): p. 213–225. Babusikova, E., et al., Oxidative damage and bronchial asthma. Respiratory Diseases. Rijeka: InTech, 2012: p. 151 − 76. Li, Y. and G.P. Li, Oxidative stress in asthma: a distinct clinical and pathologic feature? J Biol Regul Homeost Agents, 2016. 30 (4): p. 1053–1057. Demirtas, M.S., Erdal, H., Kilicbay, F. et al. Association between thiol-disulfide hemostasis and transient tachypnea of the newborn in late-preterm and term infants. BMC Pediatr 23 , 135 (2023). https://doi.org/10.1186/s12887-023-03936-z Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 02 Apr, 2025 Reviewers invited by journal 20 Mar, 2025 Editor invited by journal 28 Feb, 2025 Editor assigned by journal 27 Feb, 2025 Submission checks completed at journal 27 Feb, 2025 First submitted to journal 21 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6077681","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":422824578,"identity":"fbd966ec-175d-4967-9a17-7b502fea3ad0","order_by":0,"name":"Hacer Efnan Melek Arsoy","email":"data:image/png;base64,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","orcid":"","institution":"Sakarya University","correspondingAuthor":true,"prefix":"","firstName":"Hacer","middleName":"Efnan Melek","lastName":"Arsoy","suffix":""},{"id":422824579,"identity":"5aeb6995-8dde-45b3-a4db-3799480654e4","order_by":1,"name":"Bahri ELMAS","email":"","orcid":"","institution":"Sakarya University","correspondingAuthor":false,"prefix":"","firstName":"Bahri","middleName":"","lastName":"ELMAS","suffix":""},{"id":422824580,"identity":"2a817992-666a-4625-a848-7f8ba0674077","order_by":2,"name":"Öner ÖZDEMİR","email":"","orcid":"","institution":"Sakarya University","correspondingAuthor":false,"prefix":"","firstName":"Öner","middleName":"","lastName":"ÖZDEMİR","suffix":""},{"id":422824581,"identity":"b3c5de64-c24e-462c-8c76-b060ba2b4d13","order_by":3,"name":"Hayrullah YAZAR","email":"","orcid":"","institution":"Sakarya University","correspondingAuthor":false,"prefix":"","firstName":"Hayrullah","middleName":"","lastName":"YAZAR","suffix":""},{"id":422824582,"identity":"18f5d2d5-a27b-4420-b2d5-0ed4917bd757","order_by":4,"name":"Ceylan BAL","email":"","orcid":"","institution":"Ankara Yildirim Beyazit University","correspondingAuthor":false,"prefix":"","firstName":"Ceylan","middleName":"","lastName":"BAL","suffix":""},{"id":422824583,"identity":"c3713dd3-038a-473c-a295-4e3b7f3c19a0","order_by":5,"name":"Özcan EREL","email":"","orcid":"","institution":"Ankara Yildirim Beyazit University","correspondingAuthor":false,"prefix":"","firstName":"Özcan","middleName":"","lastName":"EREL","suffix":""}],"badges":[],"createdAt":"2025-02-21 08:38:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6077681/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6077681/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77697525,"identity":"0f74f72b-67bc-41ef-915a-cbb043fe029d","added_by":"auto","created_at":"2025-03-04 10:41:07","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":175531,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operator characteristics curve evaluating thiol/disulfide homeostasis parameters and TOS thresholds for asthma. TOS: Total oxidant status\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6077681/v1/ec1c5da32b7b39d78477e7b2.jpeg"},{"id":77697946,"identity":"978e5c76-3d72-4772-bd2d-e50436b4e74d","added_by":"auto","created_at":"2025-03-04 10:49:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1020375,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6077681/v1/ab16b602-83cf-4680-ad82-49a97b72d337.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation Of Oxidative Stress Parameters In Asthmatic Children: A Case-Control Study","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eBronchial asthma, the most prevalent chronic respiratory condition among children and continues to rise in prevalence, particularly in developing nations [1, 2]. Asthma is characterized by persistent inflammation and and airway structural changes, asthma is widely recognized as a chronic inflammatory disease despite gaps in understanding its exact pathological origins [3, 4].\u003c/p\u003e \u003cp\u003eOxidative stress, a critical factor in aging and various pathologies, results from an imbalance between pro-oxidants like reactive oxygen species (ROS) and reactive nitrogen species (RNS), and antioxidant defenses such as enzymatic (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (glutathione, vitamins C, E, and A, bilirubin) [1, 5, 6] [7, 8]. Studies reveal a strong association between asthma severity and elevated oxidative stress, with ROS contributing to progressive airway deterioration[1, 9].\u003c/p\u003e \u003cp\u003eThiol groups in cellular proteins, containing sulfhydryl groups, protect against oxidative damage by forming disulfide bonds through oxidation, which are subsequently reduced to regenerate thiols. This cycle maintains a dynamic thiol/disulfide homeostasis crucial for antioxidant defense, detoxification, cell signaling, apoptosis, and enzymatic regulation [10] [11] [12] [13]. Recently, thiol/disulfide homeostasis has emerged as a novel oxidative stress marker in diseases like asthma [14, 15].\u003c/p\u003e \u003cp\u003eLimited data exist on oxidant-antioxidant status, particularly dynamic thiol/disulfide homeostasis, in pediatric asthma patients. These compounds may influence etiopathogenesis, disease severity, and control in pediatric asthma. This study aims to evaluate oxidant and antioxidant markers, including thiol/disulfide parameters, in asthmatic children and healthy controls, and investigate the relationship between oxidative stress, asthma severity, and disease control.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Data collection steps and tools\u003c/h2\u003e \u003cp\u003eThis case-control study was conducted in the Pediatric Immunology and Allergy Department of xxx University Research and Training Hospital (June\u0026ndash;December 2016). The patient group included children aged 6\u0026ndash;17 years diagnosed with asthma, while the control group comprised age- and sex-matched healthy children referred for routine pre-operative evaluations. Participants were from non-smoking households, and exclusions included children under six, those with transient wheeze, comorbidities, recent infections, or using medications influencing oxidative status.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Data collection steps and tools\u003c/h2\u003e \u003cp\u003eThe age and sex data of all participants were recorded. In the asthma group, data on asthma duration, lung function tests, attack frequency, daytime symptoms, rescue treatment needs, and medications used were also collected\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1. Asthma diagnosis and classification\u003c/h2\u003e \u003cp\u003e The Global Initiative for Asthma (GINA) 2014 guidelines [16] were used in asthma diagnosis and classification. [17]. Patients were classified with GINA criteria as uncontrolled, partially-controlled, and controlled. Severity of asthma was determined using clinical signs and changes in spirometry values.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2. Laboratory analysis\u003c/h2\u003e \u003cp\u003eAll laboratory measurements were conducted in certified biochemistry laboratories using calibrated devices per manufacturer instructions. Peripheral venous blood (5 mL) was collected from asthmatic children upon admission and from healthy controls during routine visits. After centrifugation at 1500 rpm for 10 minutes, serum samples were stored at \u0026minus;\u0026thinsp;80\u0026deg;C until analysis.\u003c/p\u003e \u003cp\u003eThiol/disulfide status was assessed using the Erel and Neselioglu method [18], reducing disulfide bonds to free thiols, followed by neutralization with formaldehyde. Thiol levels were measured with DTNB, and disulfide levels were calculated as half the difference between total and native thiols. Ratios for disulfide/native thiol, disulfide/total thiol, and native/total thiol were determined with an automated analyzer (Cobas 501; Roche Diagnostics). Laboratory staff were blinded to patient data.\u003c/p\u003e \u003cp\u003eTotal antioxidant capacity (TAC) and total oxidant status (TOS) were measured using Rel Assay Diagnostics kits on an automated analyzer (Architect C16000; Abbott Laboratories). TAC was expressed as mmol Trolox equivalent/L, TOS as \u0026micro;mol H2O2 equivalent/L, and oxidative stress index (OSI) was calculated as OSI = (TOS/TAC) \u0026times; 100 after converting TAC to \u0026micro;mol/L [19].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Outcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was comparing oxidative stress parameters between asthmatic and non-asthmatic children. Secondary outcomes included exploring the relationships between asthma severity, asthma control status, and oxidative stress parameters.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics summarized participant characteristics. The Kolmogorov-Smirnov and Shapiro-Wilk tests assessed numerical variable distributions. Student\u0026rsquo;s t-test, the Mann-Whitney U test, analysis of variance (ANOVA), and the Kruskal-Wallis \u0026#119867;-test were used as appropriate to compare data between groups. Categorical variables were compared using the chi-squared or Fisher\u0026rsquo;s exact chi-squared test. Receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of thiol/disulfide parameters for asthma prediction. Step-wise multivariable logistic regression identified independent asthma risk predictors. Statistical analyses were performed with IBM SPSS Statistics (Version 20.0; IBM Corp., 2011), and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was deemed statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eA total of 102 subjects, consisting of 60 asthmatic children (asthma group), and 42 healthy controls, were included in the study. The mean age of the control group was 12.66 (2.35) years and the male-to-female ratio was 28/32. The mean age of the asthma group was 11.77 (2.56) years, and the male-to-female ratio was 14/28. There was no significant difference between the groups in terms of age (p\u0026thinsp;=\u0026thinsp;0.080) or sex distribution (p\u0026thinsp;=\u0026thinsp;0.178). In the asthma group, mean native thiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), total thiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), disulfide (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels, TOS (p\u0026thinsp;=\u0026thinsp;0.001) and TAC (p\u0026thinsp;=\u0026thinsp;0.050) values, disulfide/native thiol (p\u0026thinsp;=\u0026thinsp;0. 001) and disulfide/total thiol (p\u0026thinsp;=\u0026thinsp;0.002) ratios were significantly higher, while native thiol/total thiol ratio was significantly lower (p\u0026thinsp;=\u0026thinsp;0.002) than the control group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of control and asthma groups in terms of demographic data, biochemical and oxidative stress parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsthma (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.66 (2.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.77 (2.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, Male/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e404.719 (53.258)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e460.860 (50.723)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e440.764 (54.522)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e509.698 (56.381)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.022 (3.016)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.419 (7.046)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Native Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.517 (0.944)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.316 (1.512)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.129 (0.776)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.772 (1.218)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.74 (1.553)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.455 (2.437)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOS (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.050 (20.501)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118.050 (30.855)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.494 (0.218)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.590 (0.254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.050\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOSI ([TOS/TAC] x 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.898 (1.833)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.593 (2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eValues were represented as frequency, mean (SD), median (min-max). P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance. Student t test, Mann-Whitney U, X^2\u003c/p\u003e \u003cp\u003eAbbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThiol and disulfide values/ratios, as well as TOS, were found to have significant discriminatory capacity in detecting asthmatic patients. Among these, native thiol with a cut-off value of 415.1 [AUC (95% CI):0.775 (0.684\u0026ndash;0.867); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; sensitivity: 81.7%; specificity: 61.9%], total thiol with a cut-off value of 449.35 [AUC (95% CI): 0.808 (0.725\u0026ndash;0.892); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; sensitivity: 85%; specificity: 61.9%], disulfide with a cut-off value of 21.875 [AUC (95% CI): 0.816 (0.729\u0026ndash;0.903); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; sensitivity: 66.7%; specificity: 97.6%], were found to have the most notable ROC results (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReceiver operator curve evaluating thiol disulfide homeostasis parameters and TOS thresholds for asthma\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAUC (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOptimum Cut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.775 (0.684\u0026ndash;0.867)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e415.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.808 (0.725\u0026ndash;0.892)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e449.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.816 (0.729\u0026ndash;0.903)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Native Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.689 (0.586\u0026ndash;0.793)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.689 (0.586\u0026ndash;0.793)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOS (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.645 (0.538\u0026ndash;0.751)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eThe AUC values of TAC, OSI and Native Thiol / Total Thiol were below 0.6.\u003c/p\u003e \u003cp\u003eAbbreviations: AUC: Area Under Curve, CI: Confidence interval, TOS: Total oxidant status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRegression analysis and independent risk factors predicting asthma.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBeta (SE)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e95% CI for OR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(-) 0.074 (0.033)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.091 (0.032)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e(-)2 likelihood: 82.969, Nagelkerke r2\u0026thinsp;=\u0026thinsp;0.564, \u0026#119901; \u0026lt; 0.001. Native thiol, total thiol, TOS and TAC are included in the stepwise logistic regression model. \u0026#119901; \u0026lt; 0.05 statistical significance.\u003c/p\u003e \u003cp\u003eAbbreviations: CI: Confidence Interval, OR: Odds Ratio, SE: Standard Error\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMultivariable logistic regression revealed that native thiol (OR: 0.929, 95% CI: 0.871\u0026ndash;0.99, p\u0026thinsp;=\u0026thinsp;0.023) and total thiol (OR: 1.095, 95% CI: 1.029\u0026ndash;1.165, p\u0026thinsp;=\u0026thinsp;0.004) were independently associated with the high risk of asthma. In other words, 1 unit of increase in total thiol level was associated with a 1.095-fold increase in the risk of asthma. On the other hand, 1 unit of increase in native thiol level was associated with lower risk of asthma (0.929-fold). The changes in TOS and TAC values were not found to be independently associated with asthma risk (p\u0026thinsp;\u0026gt;\u0026thinsp;0.005) (\u003cb\u003eTablo 3\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eFinally, no significant difference was found between intermittent, mild and moderate asthmatics in terms of examined laboratory variables (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, patients with controlled asthma had significantly higher TOS levels than those with partially-controlled disease (p\u0026thinsp;=\u0026thinsp;0.037). Apart from this, no significant parameter differences were observed between groups divided with respect to disease control status (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory parameters according to severity of asthma.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAsthma severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntermittent (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e484.600 (38.780)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e455.019 (52.132)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e457.895 (52.635)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e539.550 (46.758)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e500.151 (57.665)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e509.563 (55.968)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.159\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.475 (5.871)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.566 (6.296)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.834 (8.136)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Native Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.650 (0.989)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.968 (1.342)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.706 (1.889)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.064 (0.788)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.493 (1.106)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.074 (1.496)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.871 (1.575)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.013 (2.212)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89.851 (2.992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOS (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131.290 (37.761)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.400 (27.706)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121.930 (30.640)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.620 (0.246)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.591 (0.256)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.572 (0.265)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.891\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOSI ([TOS/TAC] x 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.176 (2.149)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.185 (2.251)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.953 (2.350)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eValues were represented as mean (SD), median (min-max). P values of \u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance\u003c/p\u003e \u003cp\u003eAbbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory findings according to asthma control status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eAsthma control level\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControlled (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePartially-Controlled\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUncontrolled (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e468 (65.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e466.178 (43.701)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e447.54 (54.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Thiol (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e520.44 (75.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e513.378 (45.478)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e497.58 (64.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.22 (8.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.600 (5.081)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.02 (9.274)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Native Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.59 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.103 (1.241)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.567 (1.904)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisulfide/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.994 (1.338)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.609 (1.0129)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.960 (1.504)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Thiol/Total Thiol (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.01 (2.676)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.781 (2.025)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.078 (3.009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOS (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.28 (105\u0026ndash;196) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106.27 (71\u0026ndash;176)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114.3 (77\u0026ndash;180)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.513 (1.258\u0026ndash;1.953)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.554 (1.054\u0026ndash;2.111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.529 (1.210\u0026ndash;2.099)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOSI ([TOS/TAC] x 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.412 (5.997\u0026ndash;11.782)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.426 (4.348\u0026ndash;11.422)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.065 (5.353\u0026ndash;13.463)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eValues were represented as mean (SD), median (min-max). P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e: different from partly controlled\u003c/p\u003e \u003cp\u003eAbbreviations: OSI: Oxidative stress index, TAC: Total antioxidant capacity, TOS: Total oxidant status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eAsthma is the leading chronic inflammatory lung disease in children, with oxidative stress playing a key role in airway inflammation [13]. This study, aimed at exploring the link between pediatric asthma and oxidative stress, found that native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, TOS, and TAC levels were significantly higher, while native thiol/total thiol was lower in asthmatic children compared to healthy controls. Disulfide emerged as the most distinctive marker for asthma, and elevated native and total thiol levels were identified as independent risk factors for asthma presence. However, no variable was linked to asthma severity. Notably, controlled asthmatic children had significantly lower TOS levels than those with partially controlled disease.\u003c/p\u003e \u003cp\u003eAsthma is closely associated with oxidative stress, which contributes to airflow obstruction, airway hyperreactivity, and remodeling. Antioxidants are essential for neutralizing reactive oxygen and nitrogen species (ROS/RNS) generated during normal metabolism, maintaining airway balance. In asthma, elevated ROS/RNS and reduced enzymatic antioxidants result in decreased antioxidant activity, a hallmark of the disease [20]. Thiols, crucial components of the plasma antioxidant system, include albumin, glutathione (GSH), thioredoxin, cysteine, and homocysteine [13]. Assessing thiol/disulfide homeostasis offers insights into oxidative stress, though studies comparing these markers in asthmatic vs. healthy children remain limited. This study found significantly higher levels of native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, TOS, and TAC in asthmatic children, with a lower native thiol/total thiol ratio. ROC analysis identified total thiol\u0026thinsp;\u0026gt;\u0026thinsp;49.35 as the most sensitive marker and disulfide\u0026thinsp;\u0026gt;\u0026thinsp;21.875 as the most specific. Native thiol and total thiol were independent risk factors for asthma. In a recent study, children with well-controlled asthma had decreased serum levels of thiol groups, tryptophan, and TAC compared to healthy children, indicating persistent oxidative stress even in controlled asthma [21]. Another study found significantly reduced superoxide dismutases (SOD) and glutathione peroxidases (GPx) activities alongside elevated malondialdehyde (MDA) levels in asthmatic children [22]. Fabian et al. reported lower plasma antioxidant levels, including vitamins A and E, selenium, and coenzyme Q10, and higher MDA levels in asthmatic children compared to controls, along with reduced TAC [23]. A Turkish study revealed that asthmatic children had higher MDA and lower reduced GSH levels, with asthma identified as an independent oxidative stress factor [24]. Celik et al. demonstrated elevated MDA and reduced GSH in nasal and oral exhaled breath samples of asthmatic children [25]. Similarly, a case-control study showed increased serum oxidant markers like asymmetric dimethylarginine and MDA, along with decreased paraoxonase activity in asthmatic children compared to healthy controls [26].\u003c/p\u003e \u003cp\u003eSevere, treatment-resistant asthma in children remains challenging to manage despite high-dose corticosteroids. While mild-to-moderate asthma responds to low-dose inhaled corticosteroids, the underlying mechanisms of severe asthma remain unclear, with excessive free radical generation as a key feature. [27]. Monitoring oxidative stress by-products has been suggested as a potential indicator of asthma severity [28], with studies linking oxidative stress markers to poorer clinical control, increased severity, and reduced lung function [29]. The extent of bronchial hyperreactivity has also been associated with reactive ROS levels [30]. In this study, none of the oxidant or antioxidant parameters were linked to asthma severity. Nar et al. found a positive correlation between forced exhalation volume in one second (FEV1) and forced vital capacity (FVC) with native and total thiol levels, though no correlation with FEV1/FVC or other thiol/disulfide parameters. Disulfide levels correlated positively with positive expiratory pressure [13]. Dilek et al. compared newly diagnosed asthma patients (Group I) and those on montelukast therapy for over 4 months (Group II), finding lower plasma total thiol in Group I, while Group II levels resembled controls. No significant difference in TAS or total thiol was observed between Groups I and II [31]. Anne et al. hypothesized that Nrf2 dysfunction in severe asthma depletes thiol reserves. Their study revealed increased oxidation and reduced GSH and cysteine levels in severe asthma, with impaired Nrf2 function despite elevated Nrf2 expression [27]. Ammar et al. found spirometry correlated with SOD activity but not with MDA, GSH, or GPx [32]. Another study noted a negative correlation between FEV1 (% predicted) and MDA, and a positive correlation with GSH [33]. Dut et al. observed no difference in MDA and GSH levels between mild and moderate asthmatics [24]. A case-control study found higher serum oxidants and lower antioxidants in severe asthma, identifying MDA as a strong predictor of severity [26]. Clusterin, an oxidative stress indicator with antioxidant properties, is elevated in severe asthma and inversely correlates with lung function [34].\u003c/p\u003e \u003cp\u003eOxidative stress drives asthma development and persistence by inducing excessive ROS/RNS production, particularly during allergen exposure, infections, and pollution. This promotes airway remodeling, reduces treatment response, and worsens clinical outcomes, especially in uncontrolled asthma. [1]. In the present study, children with controlled asthma had significantly lower TOS levels than those with partially controlled asthma, though no difference was found between uncontrolled and other groups. This may be due to the small number of patients. Stephenson et al. linked cysteine oxidation with elevated oxidative stress, reduced glucocorticoid receptor activity, and poorer asthma control. Children with high cysteine oxidation exhibited increased ROS, elevated CCL3 and CXCL1 expression, and diminished glucocorticoid responsiveness [35]. In a prospective study, uncontrolled asthma was associated with elevated MDA, advanced oxidation protein products, increased SOD activity, and decreased GSH and GPx levels [32]. Karadogan et al. found that MDA and protein carbonyl levels were higher in uncontrolled asthma compared to controlled groups, while catalase activity was elevated in partially controlled asthma. TAC was significantly lower in uncontrolled asthma, with a negative correlation between asthma control scores and oxidative stress biomarkers [33]. Fernando et al. reported increased nitric oxide metabolites in asthma patients regardless of control status. TAC levels were lower in poorly controlled asthma but showed no difference between well-controlled patients and healthy controls, suggesting higher TAC may aid asthma control [36]. Some studies propose paraoxonase and TOS as biomarkers for identifying uncontrolled asthma in children [37].\u003c/p\u003e \u003cp\u003eAs mentioned above, numerous investigations have highlighted that cells involved in airway inflammation in asthma serve as a significant source of ROS in affected individuals [38]. The oxidative damage inflicted upon biomolecules can yield both functional and structural repercussions, exerting a pivotal influence on the onset, persistence, and outcomes of asthma across all phenotypes or endotypes. Given the fundamental role of inflammation in the pathogenesis of all forms and subtypes of asthma, ROS and RNS, alongside compromised antioxidant defense mechanisms and biomolecular oxidation, give rise to a myriad of consequences. These include heightened release of arachidonic acid from cell membranes and the generation of inflammatory markers, augmented hyperreactivity and contraction of airway smooth muscle, increased vascular permeability leading to airway edema, elevated bronchial hyperresponsiveness and mucus secretion, enhanced synthesis of pro-inflammatory cytokines and chemoattractants, triggered release of tachykinins and neurokinins fostering neurogenic inflammation, and impaired responsiveness to bronchodilators [39]. Moreover, oxidative damage to DNA and histones may induce epigenetic alterations, diminishing the efficacy of anti-asthmatic medications, such as corticosteroids [40]. Our data found increased both oxidant and antioxidant markers in pediatric asthmatic patients independent of disease severity and control status. These results largely contradict the existing literature data. Because in most of the studies whose results are presented above, it is seen that the levels of oxidant parameters increase and the levels of antioxidant parameters decrease in asthma. In addition, it has been shown in many studies that oxidative stress increases in uncontrolled asthma compared to controlled asthma and as the severity of asthma increases. There may be several possible reasons for our results. (i) The increase in both oxidant and antioxidant markers in patients may be the result of a compensatory mechanism against increased oxidative stress. (ii) Differences in the measurement methods of thiol/disulfide homeostasis parameters may have led to different results. The measurement method we used is thought to give more reliable results compared to previous measurement methods [1]. However, study designs comparing different measurement methods are necessary to support this hypothesis. (iii) There is a possibility that asthma treatments may affect oxidative stress parameters and that there may be treatment differences between the study populations. Comprehensive studies including treatment details are required. (iv) The number of studies investigating thiol/disulfide homeostasis parameters and their relationship with asthma severity and control status in pediatric asthmatics is very limited. The disulfide level is expected to increase and the thiol level decreases under oxidative stress. But both disulfide levels and thiol levels observed in our study were higher than those in healthy subjects. These findings may be explained by the factors affecting the thiol-disulfide balance except oxidative stress such as the rates of the thiol-disulfide exchange reactions, thiol oxidation by ROS and possible repair processes, enzymatic extracellular degradation of GSH and liver release of thiol-containing molecules. The possible effects of possible pathophysiological differences between pediatric and adult asthma on the results obtained should be investigated in more comprehensive studies. (v) [41]. The different number of participants between the groups may have affected the statistical findings.\u003c/p\u003e"},{"header":"5. LIMITATIONS","content":"\u003cp\u003eThe single-center design of this study limits external validity. The number of participants is relatively small. The different number of subjects between the groups may have had an effect on the statistical analyses. The number of patients with severe asthma was very small, and therefore, these patients were not examined as a separate group. It is also evident that clarifying the mechanistic relationships between oxidative stress and pediatric asthma necessitates longitudinal follow-up of oxidative stress markers. This was not done in the current study. The details about some factors that may have an impact on oxidative stress marker levels were not considered, including nutritional status, environmental factors, duration of asthma, further details of asthma treatment, time of last asthma attack, and attack periodicity. Other parameters of oxidative stress such as SOD, GPx, GSH and MDA were not examined.\u003c/p\u003e"},{"header":"6. CONCLUSION","content":"\u003cp\u003eData from the current study reveals that native thiol, total thiol, disulfide, disulfide, disulfide/native thiol, disulfide/total thiol, TOS and TAC were significantly higher and native thiol/total thiol was significantly lower in asthmatic children compared to healthy ones. High disulfide was the most valuable parameter for predicting asthmatic children. High native thiol and total thiol were independent risk factors for asthma. There was no significant association between oxidative stress parameters and asthma severity and control status. Clarification of the relationship between oxidative stress parameters, especially those related to thiol/disulfide homeostasis, and pediatric asthma may allow the development of new treatment regimens to control the onset and severity of the disease and to treat persistent asthma. However, further studies seem to be needed to clarify the pathophysiological links between oxidative stress and the onset, severity and controlling of pediatric asthma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFEV1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Forced exhalation volume in one second \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFVC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Forced vital capacity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGSH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp; Glutathione\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGPx\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Glutathione peroxidases\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGINA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp; The Global Initiative for Asthma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;MDA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp; Malondialdehyde\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOSI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Oxidative stress index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eROS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Reactive oxygen species\u003c/p\u003e\n\u003cp\u003eRNS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Reactive nitrogen species\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSOD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Superoxide dismutases\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTAC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Total antioxidant capacity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTOS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Total oxidant status\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no acknowledgments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHEMA and BE are responsible for conceptualizing the study framework, drafting the manuscript, and conducting comprehensive critical revisions. BE performed statistical analyses. BE and ÖÖ actively participated in patient care and clinical data collection, contributing to the interpretation of clinical outcomes. HY, CB, and ÖE developed the data collection strategy and conducted laboratory procedures with detailed validation steps. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Datasets is avaible. The patients data is avaible from the correspondng author on reasonable request ([email protected]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement /\u003c/strong\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo potential conflict of interest was reported by the authors. Manuscript contents are solely the responsibility of the authors. All other authors declare that they have no conflicts of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenerative Artificial Intelligence (AI) Disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGenerative \u0026nbsp;artificial intelligence was not used in any aspect of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors reported that there is no funding associated with the work featured in this article.\u0026nbsp;Sakarya University, will support publication of the manuscript if accepted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations and consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no Ethical Considerations. The study was initiated after approval by our local (Sakarya University) ethics committee (No: 16214662 / 050.01.04/88) and the study adhered to the Declaration of Helsinki. Informed consent was received from participants (verbal) and their parents (written), following good clinical practice guidelines. All procedures were in accordance with ethical standards and the information in the journal's manual and Declaration of Helsinki and ethical guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the parents or legal guardians of all pediatric participants prior to inclusion in the study. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJesenak, M., M. Zelieskova, and E. Babusikova, \u003cem\u003eOxidative stress and bronchial asthma in children\u0026mdash;causes or consequences?\u003c/em\u003e Frontiers in pediatrics, 2017. \u003cstrong\u003e5\u003c/strong\u003e: p. 162.\u003c/li\u003e\n\u003cli\u003eAnandan, C., et al., \u003cem\u003eIs the prevalence of asthma declining? Systematic review of epidemiological studies.\u003c/em\u003e Allergy, 2010. \u003cstrong\u003e65\u003c/strong\u003e(2): p. 152\u0026thinsp;\u0026minus;\u0026thinsp;67.\u003c/li\u003e\n\u003cli\u003eJames, A. and G. Hedlin, \u003cem\u003eBiomarkers for the Phenotyping and Monitoring of Asthma in Children.\u003c/em\u003e Curr Treat Options Allergy, 2016. \u003cstrong\u003e3\u003c/strong\u003e(4): p. 439\u0026ndash;452.\u003c/li\u003e\n\u003cli\u003eNosal, S., et al., \u003cem\u003eChanges of airway obstruction parameters in healthy children caused by mother's smoking during pregnancy.\u003c/em\u003e J Physiol Pharmacol, 2008. \u003cstrong\u003e59 Suppl 6\u003c/strong\u003e: p. 523-9.\u003c/li\u003e\n\u003cli\u003eYalcinkaya, A., et al., \u003cem\u003eOxysterol concentrations are associated with cholesterol concentrations and anemia in pediatric patients with sickle cell disease.\u003c/em\u003e Scandinavian Journal of Clinical and Laboratory Investigation, 2019. \u003cstrong\u003e79\u003c/strong\u003e(6): p. 381\u0026ndash;387.\u003c/li\u003e\n\u003cli\u003eYildirim, N., et al., \u003cem\u003eEvaluation of the relationship between intravascular hemolysis and clinical manifestations in sickle cell disease: decreased hemopexin during vaso-occlusive crises and increased inflammation in acute chest syndrome.\u003c/em\u003e Annals of Hematology, 2022. \u003cstrong\u003e101\u003c/strong\u003e(1): p. 35\u0026ndash;41.\u003c/li\u003e\n\u003cli\u003eRhee, S.G. and I.S. Kil, \u003cem\u003eMultiple Functions and Regulation of Mammalian Peroxiredoxins.\u003c/em\u003e Annu Rev Biochem, 2017. \u003cstrong\u003e86\u003c/strong\u003e: p. 749\u0026ndash;775.\u003c/li\u003e\n\u003cli\u003eTsutsui, H., S. Kinugawa, and S. Matsushima, \u003cem\u003eOxidative stress and heart failure.\u003c/em\u003e Am J Physiol Heart Circ Physiol, 2011. \u003cstrong\u003e301\u003c/strong\u003e(6): p. H2181-90.\u003c/li\u003e\n\u003cli\u003eBabusikova, E., et al., \u003cem\u003eImportance of oxidative damage in the pathogenesis of bronchial asthma in children.\u003c/em\u003e Acta Pneumol Allergol Pediatr, 2010. \u003cstrong\u003e13\u003c/strong\u003e: p. 13\u0026thinsp;\u0026minus;\u0026thinsp;7.\u003c/li\u003e\n\u003cli\u003eThomas, J.A., B. Poland, and R. Honzatko, \u003cem\u003eProtein sulfhydryls and their role in the antioxidant function of protein S-thiolation.\u003c/em\u003e Arch Biochem Biophys, 1995. \u003cstrong\u003e319\u003c/strong\u003e(1): p. 1\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eCremers, C.M. and U. Jakob, \u003cem\u003eOxidant sensing by reversible disulfide bond formation.\u003c/em\u003e J Biol Chem, 2013. \u003cstrong\u003e288\u003c/strong\u003e(37): p. 26489-96.\u003c/li\u003e\n\u003cli\u003eJones, D.P. and Y. Liang, \u003cem\u003eMeasuring the poise of thiol/disulfide couples in vivo.\u003c/em\u003e Free Radic Biol Med, 2009. \u003cstrong\u003e47\u003c/strong\u003e(10): p. 1329-38.\u003c/li\u003e\n\u003cli\u003eNar, R. and A.G. \u0026Ccedil;alış, \u003cem\u003eAssessment of dynamic thiol/disulfide homeostasis in patients with asthma.\u003c/em\u003e Journal of laboratory medicine, 2018. \u003cstrong\u003e42\u003c/strong\u003e(3): p. 99\u0026ndash;104.\u003c/li\u003e\n\u003cli\u003eAtes, I., et al., \u003cem\u003eDynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension.\u003c/em\u003e J Am Soc Hypertens, 2016. \u003cstrong\u003e10\u003c/strong\u003e(2): p. 159\u0026thinsp;\u0026minus;\u0026thinsp;66.\u003c/li\u003e\n\u003cli\u003eFidan, F., et al., \u003cem\u003eDynamic Thiol/Disulphide Homeostasis in Patients With Fibromyalgia.\u003c/em\u003e Arch Rheumatol, 2017. \u003cstrong\u003e32\u003c/strong\u003e(2): p. 112\u0026ndash;117.\u003c/li\u003e\n\u003cli\u003eReddel, H.K. and M.L. Levy, \u003cem\u003eThe GINA asthma strategy report: what's new for primary care?\u003c/em\u003e NPJ Prim Care Respir Med, 2015. \u003cstrong\u003e25\u003c/strong\u003e: p. 15050.\u003c/li\u003e\n\u003cli\u003eBehrman, R.E., R.M. Kliegman, and H.B. Jenson, \u003cem\u003eNelson textbook of pediatrics.\u003c/em\u003e 2000.\u003c/li\u003e\n\u003cli\u003eErel, O. and S. Neselioglu, \u003cem\u003eA novel and automated assay for thiol/disulphide homeostasis.\u003c/em\u003e Clin Biochem, 2014. \u003cstrong\u003e47\u003c/strong\u003e(18): p. 326\u0026thinsp;\u0026minus;\u0026thinsp;32.\u003c/li\u003e\n\u003cli\u003eYumru, M., et al., \u003cem\u003eOxidative imbalance in bipolar disorder subtypes: a comparative study.\u003c/em\u003e Prog Neuropsychopharmacol Biol Psychiatry, 2009. \u003cstrong\u003e33\u003c/strong\u003e(6): p. 1070-4.\u003c/li\u003e\n\u003cli\u003eSahiner, U.M., et al., \u003cem\u003eOxidative stress in asthma: Part of the puzzle.\u003c/em\u003e Pediatric Allergy and Immunology, 2018. \u003cstrong\u003e29\u003c/strong\u003e(8): p. 789\u0026ndash;800.\u003c/li\u003e\n\u003cli\u003eBiesiadecki, M., et al., \u003cem\u003eA Comparative Study of Oxidative Stress Biomarker Levels in Asthmatic and Non-Asthmatic Children.\u003c/em\u003e Biointerface Res. Appl. Chem, 2022. \u003cstrong\u003e13\u003c/strong\u003e: p. 280.\u003c/li\u003e\n\u003cli\u003eShokry, D.M. and S.A. El-Tarahony, \u003cem\u003eOxidant-antioxidant balance in childhood asthma.\u003c/em\u003e Egyptian Journal of Pediatric Allergy and Immunology (The), 2013. \u003cstrong\u003e11\u003c/strong\u003e(1).\u003c/li\u003e\n\u003cli\u003eFabian, E., et al., \u003cem\u003eNutritional supplements and plasma antioxidants in childhood asthma.\u003c/em\u003e Wien Klin Wochenschr, 2013. \u003cstrong\u003e125\u003c/strong\u003e(11\u0026ndash;12): p. 309\u0026thinsp;\u0026minus;\u0026thinsp;15.\u003c/li\u003e\n\u003cli\u003eDut, R., et al., \u003cem\u003eOxidative stress and its determinants in the airways of children with asthma.\u003c/em\u003e Allergy, 2008. \u003cstrong\u003e63\u003c/strong\u003e(12): p. 1605-9.\u003c/li\u003e\n\u003cli\u003eCelik, M., et al., \u003cem\u003eOxidative stress in the airways of children with asthma and allergic rhinitis.\u003c/em\u003e Pediatr Allergy Immunol, 2012. \u003cstrong\u003e23\u003c/strong\u003e(6): p. 556\u0026thinsp;\u0026minus;\u0026thinsp;61.\u003c/li\u003e\n\u003cli\u003eEl-Alameey, I.R., et al., \u003cem\u003eRelationship of Oxidant and Antioxidant Markers to Asthma Severity in Egyptian Asthmatic Children.\u003c/em\u003e Open Access Maced J Med Sci, 2017. \u003cstrong\u003e5\u003c/strong\u003e(5): p. 645\u0026ndash;650.\u003c/li\u003e\n\u003cli\u003eFitzpatrick, A.M., et al., \u003cem\u003eThiol redox disturbances in children with severe asthma are associated with posttranslational modification of the transcription factor nuclear factor (erythroid-derived 2)-like 2.\u003c/em\u003e J Allergy Clin Immunol, 2011. \u003cstrong\u003e127\u003c/strong\u003e(6): p. 1604-11.\u003c/li\u003e\n\u003cli\u003eJiang, L., et al., \u003cem\u003eMolecular characterization of redox mechanisms in allergic asthma.\u003c/em\u003e Ann Allergy Asthma Immunol, 2014. \u003cstrong\u003e113\u003c/strong\u003e(2): p. 137\u0026thinsp;\u0026minus;\u0026thinsp;42.\u003c/li\u003e\n\u003cli\u003eFatani, S.H., \u003cem\u003eBiomarkers of oxidative stress in acute and chronic bronchial asthma.\u003c/em\u003e J Asthma, 2014. \u003cstrong\u003e51\u003c/strong\u003e(6): p. 578\u0026thinsp;\u0026minus;\u0026thinsp;84.\u003c/li\u003e\n\u003cli\u003eCalhoun, W.J., et al., \u003cem\u003eEnhanced superoxide production by alveolar macrophages and air-space cells, airway inflammation, and alveolar macrophage density changes after segmental antigen bronchoprovocation in allergic subjects.\u003c/em\u003e Am Rev Respir Dis, 1992. \u003cstrong\u003e145\u003c/strong\u003e(2 Pt 1): p. 317\u0026thinsp;\u0026minus;\u0026thinsp;25.\u003c/li\u003e\n\u003cli\u003eDilek, F., et al., \u003cem\u003ePlasma total thiol pool in children with asthma: Modulation during montelukast monotherapy.\u003c/em\u003e Int J Immunopathol Pharmacol, 2016. \u003cstrong\u003e29\u003c/strong\u003e(1): p. 84\u0026thinsp;\u0026minus;\u0026thinsp;9.\u003c/li\u003e\n\u003cli\u003eAmmar, M., et al., \u003cem\u003eOxidative stress in patients with asthma and its relation to uncontrolled asthma.\u003c/em\u003e J Clin Lab Anal, 2022. \u003cstrong\u003e36\u003c/strong\u003e(5): p. e24345.\u003c/li\u003e\n\u003cli\u003eKaradogan, B., et al., \u003cem\u003eEvaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control.\u003c/em\u003e J Asthma, 2022. \u003cstrong\u003e59\u003c/strong\u003e(4): p. 663\u0026ndash;672.\u003c/li\u003e\n\u003cli\u003eKwon, H.S., et al., \u003cem\u003eClusterin expression level correlates with increased oxidative stress in asthmatics.\u003c/em\u003e Ann Allergy Asthma Immunol, 2014. \u003cstrong\u003e112\u003c/strong\u003e(3): p. 217\u0026thinsp;\u0026minus;\u0026thinsp;21.\u003c/li\u003e\n\u003cli\u003eStephenson, S.T., et al., \u003cem\u003eCysteine oxidation impairs systemic glucocorticoid responsiveness in children with difficult-to-treat asthma.\u003c/em\u003e J Allergy Clin Immunol, 2015. \u003cstrong\u003e136\u003c/strong\u003e(2): p. 454\u0026thinsp;\u0026minus;\u0026thinsp;61.e9.\u003c/li\u003e\n\u003cli\u003eFernando, Y., et al., \u003cem\u003eDifferences in serum markers of oxidative stress in well controlled and poorly controlled asthma in Sri Lankan children: a pilot study.\u003c/em\u003e Allergy Asthma Clin Immunol, 2020. \u003cstrong\u003e16\u003c/strong\u003e: p. 66.\u003c/li\u003e\n\u003cli\u003eEmin, O., A. Hasan, and D.M. Rusen, \u003cem\u003ePlasma paraoxonase, oxidative status level, and their relationship with asthma control test in children with asthma.\u003c/em\u003e Allergol Immunopathol (Madr), 2015. \u003cstrong\u003e43\u003c/strong\u003e(4): p. 346\u0026thinsp;\u0026minus;\u0026thinsp;52.\u003c/li\u003e\n\u003cli\u003eAndreadis, A.A., et al., \u003cem\u003eOxidative and nitrosative events in asthma.\u003c/em\u003e Free Radical Biology and Medicine, 2003. \u003cstrong\u003e35\u003c/strong\u003e(3): p. 213\u0026ndash;225.\u003c/li\u003e\n\u003cli\u003eBabusikova, E., et al., \u003cem\u003eOxidative damage and bronchial asthma.\u003c/em\u003e Respiratory Diseases. Rijeka: InTech, 2012: p. 151\u0026thinsp;\u0026minus;\u0026thinsp;76.\u003c/li\u003e\n\u003cli\u003eLi, Y. and G.P. Li, \u003cem\u003eOxidative stress in asthma: a distinct clinical and pathologic feature?\u003c/em\u003e J Biol Regul Homeost Agents, 2016. \u003cstrong\u003e30\u003c/strong\u003e(4): p. 1053\u0026ndash;1057.\u003c/li\u003e\n\u003cli\u003eDemirtas, M.S., Erdal, H., Kilicbay, F. \u003cem\u003eet al.\u003c/em\u003e Association between thiol-disulfide hemostasis and transient tachypnea of the newborn in late-preterm and term infants. \u003cem\u003eBMC Pediatr\u003c/em\u003e\u003cstrong\u003e23\u003c/strong\u003e, 135 (2023). https://doi.org/10.1186/s12887-023-03936-z\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Child, asthma, oxidative stress, oxidants, antioxidants, disulfides","lastPublishedDoi":"10.21203/rs.3.rs-6077681/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6077681/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo compare some oxidative stress parameters between pediatric asthmatic individuals and healthy children, and to investigate the relationship between pediatric asthma severity and control status with oxidative stress.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis case-control study was performed between June\u0026ndash;December 2016, including children with asthma and healthy controls. Asthmatic patients were classified according to severity and disease-control status. Asthmatic children and controls were compared in terms of native thiol, total thiol, disulfide levels, disulfide/native thiol ratio, disulfide/total thiol ratio, native thiol/total thiol ratio, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI). Patients classified according to asthma severity and control status were also analyzed in terms of these parameters.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 102 subjects, consisting of 60 asthmatic children (asthma group), and 42 non-asthmatic children (the control group), were included in the study. There was no significant difference between the asthma and control groups in terms of age (p\u0026thinsp;=\u0026thinsp;0.080) and sex distribution (p\u0026thinsp;=\u0026thinsp;0.178). In the asthma group, mean native thiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), total thiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), disulfide (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels, TOS (p\u0026thinsp;=\u0026thinsp;0.001) and TAC (p\u0026thinsp;=\u0026thinsp;0.050) values, disulfide/native thiol (p\u0026thinsp;=\u0026thinsp;0. 001) and disulfide/total thiol (p\u0026thinsp;=\u0026thinsp;0.002) ratios were significantly higher and native thiol/total thiol ratio was significantly lower (p\u0026thinsp;=\u0026thinsp;0.002) than the control group. Native thiol, total thiol, and disulfide levels had the best discriminatory ability to detect asthma. Multivariable logistic regression identified native thiol and total thiol as being independently associated asthma presence.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOxidative stress appears to be associated with the pathophysiology of pediatric asthma, but more studies are needed to confirm the relationship between oxidative stress and asthma severity and control status.\u003c/p\u003e","manuscriptTitle":"Evaluation Of Oxidative Stress Parameters In Asthmatic Children: A Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-04 10:41:03","doi":"10.21203/rs.3.rs-6077681/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"164963045870077307015376904780504683297","date":"2025-04-02T07:55:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-20T04:56:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-02-28T06:06:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-27T10:24:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-02-27T10:22:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-02-21T08:33:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"39135257-6c34-44e8-82b0-4fb61a1f6a0e","owner":[],"postedDate":"March 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-03-04T10:41:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-04 10:41:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6077681","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6077681","identity":"rs-6077681","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}