Browsing by Author "Milenković, Branislava (23005307400)"

The primary role of alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as common (Z and S) and rare (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.

The primary role of alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as common (Z and S) and rare (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.

Tumour necrosis factor alpha (TNFalpha) has a central role in the host immune response to mycobacterial infection.TNFalpha blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB) was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohn's disease. Five years before admission, the patient was diagnosed with Crohn's disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x-ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB.

Introduction Lung cancer is the leading cause of death from malignancy in Serbia. Objective This is a retrospective analysis of lung cancer epidemiological changes regarding to its histological type and patients' age of both genders. Data were based on surgically treated lung cancer patients from 1985 to 2005. Methods Data were collected from 972 pathohistological reports of operated patients of both genders divided into age groups. Histological types of lung cancer were distributed in four major groups: squamous cell cancer (SCC), adenocarcinoma (AC), small cell cancer (SCLC) and other rare histological types. Both genders together and separately were analysed. Chi-square with the level of significance p<0.05 and chi-square test for trends were used as statistical methods. Results SCC predominated in both genders; in 44.7% females and 68.0% males. AC was less frequently diagnosed (21.8%) than SCC (64.0%) in both genders and all age groups. The most frequently operated patients were aged between 51 and 60 years (36.6%) with SCC and AC predominance. Three patients with SCLC were operated in 61-70 age-group. In age-group up to 30 years, three (0.5%) patients were operated on for SCC and other rare lung tumours, respectively. Predominance of other rare lung tumours was established in 51-60 age-group, 25% of patients of both genders. Conclusion SCC is the most frequent histological type of lung cancer found in all age groups and in both genders of surgically treated patients.

Background: The SNP rs855791 has been linked to increased hepcidin levels, variations in serum iron, transferrin saturation and red blood cell indices. Our goal was to determine the prevalence of this polymorphism among COPD patients and to assess its impact on iron status parameters in patients with stable COPD. Methods: We analysed iron status parameters and genetic data from 29 COPD patients with wild-type genotype (WT group) and 65 COPD patients with either homozygous or heterozygous genotype (HH group). Additionally, the prevalence of SNP rs855791 was assessed in 192 volunteers. Results: The frequency distribution of SNP rs855791 was comparable between the COPD patients and control subjects (p=0.791). Iron status parameters were within their respective reference values and showed neither statistically nor clinically significant difference between the WT and HH group of COPD patients. However, after excluding patients with (sub)clinical vitamin B12 deficiency and/or hypoxemia, WT group of patients exhibited significantly lower erythropoietin levels (p=0.015). The area under the curve for erythropoietin was 0.688 (95% CI: 0.545–0.830, p=0.015), with an optimal cut-off of 9.74, sensitivity of 61.2% (95% CI: 58.1–64.3) and specificity of 65.0% (95% CI: 61.8–68.3). Conclusions: Iron status parameters do not differ between WT and HH groups of stable COPD patients. Statistical but not clinical difference in EPO levels was observed in a subgroup of patients. In addition to promoting erythropoiesis, EPO may regulate hepcidin levels and thus influence the development of iron deficiency and/or anaemia. Also, EPO’s direct effect on immune cells and down-regulation of inflammatory reactions should be considered in this context. © 2025 Society of Medical Biochemists of Serbia. All rights reserved.

Background: The SNP rs855791 has been linked to increased hepcidin levels, variations in serum iron, transferrin saturation and red blood cell indices. Our goal was to determine the prevalence of this polymorphism among COPD patients and to assess its impact on iron status parameters in patients with stable COPD. Methods: We analysed iron status parameters and genetic data from 29 COPD patients with wild-type genotype (WT group) and 65 COPD patients with either homozygous or heterozygous genotype (HH group). Additionally, the prevalence of SNP rs855791 was assessed in 192 volunteers. Results: The frequency distribution of SNP rs855791 was comparable between the COPD patients and control subjects (p=0.791). Iron status parameters were within their respective reference values and showed neither statistically nor clinically significant difference between the WT and HH group of COPD patients. However, after excluding patients with (sub)clinical vitamin B12 deficiency and/or hypoxemia, WT group of patients exhibited significantly lower erythropoietin levels (p=0.015). The area under the curve for erythropoietin was 0.688 (95% CI: 0.545–0.830, p=0.015), with an optimal cut-off of 9.74, sensitivity of 61.2% (95% CI: 58.1–64.3) and specificity of 65.0% (95% CI: 61.8–68.3). Conclusions: Iron status parameters do not differ between WT and HH groups of stable COPD patients. Statistical but not clinical difference in EPO levels was observed in a subgroup of patients. In addition to promoting erythropoiesis, EPO may regulate hepcidin levels and thus influence the development of iron deficiency and/or anaemia. Also, EPO’s direct effect on immune cells and down-regulation of inflammatory reactions should be considered in this context. © 2025 Society of Medical Biochemists of Serbia. All rights reserved.

Introduction: Erythrocyte indices LHD and Maf are complementary parameters to complete blood count and have been shown as reliable iron deficiency markers in different clinical settings. The aim of the study was to assess diagnostic performances of LHD and Maf in detecting iron deficiency in nonanaemic stable COPD patients. Methods: A total of 93 nonanaemic stable COPD patients were classified as either iron deficient (ID, N = 15) or non-iron deficient (non-ID, N = 78). Iron deficiency was defined as a ferritin level < 100 μg/L with a transferrin saturation (TSAT) <20%. A complete blood count, including LHD and Maf as well as other relevant inflammation and iron status parameters were obtained for all participants. Results: Both LHD and Maf have shown significant differences between the ID and non-ID group with p =.003 and p =.007 respectively. The AUC for LHD was.744 (95% CI:.626–.863, p =.003) with the best cut-off of 5.85 and sensitivity of 80% (95% CI: 76.0–84.0) and specificity of 61.5% (95% CI: 58.4–64.6). The AUC for Maf was.707 with optimal cut-off value 12.65 and sensitivity of 83.3% (95% CI: 79.1–87.5) and specificity of 60.0% (95% CI: 57.0–63.0). Furthermore, LHD performance was not affected by vitamin B12 status. Conclusion: LHD and Maf are useful for iron deficiency diagnosis in stable COPD patients. LHD was shown to be resistant to vitamin B12 deficiency, which is of substantial importance in specific patient subpopulations. Both parameters are not technology-dependant and do not require additional sample and/or reagent volume, which makes them cost-effective and convenient for everyday use. © 2023 John Wiley & Sons Ltd.

Introduction: Erythrocyte indices LHD and Maf are complementary parameters to complete blood count and have been shown as reliable iron deficiency markers in different clinical settings. The aim of the study was to assess diagnostic performances of LHD and Maf in detecting iron deficiency in nonanaemic stable COPD patients. Methods: A total of 93 nonanaemic stable COPD patients were classified as either iron deficient (ID, N = 15) or non-iron deficient (non-ID, N = 78). Iron deficiency was defined as a ferritin level < 100 μg/L with a transferrin saturation (TSAT) <20%. A complete blood count, including LHD and Maf as well as other relevant inflammation and iron status parameters were obtained for all participants. Results: Both LHD and Maf have shown significant differences between the ID and non-ID group with p =.003 and p =.007 respectively. The AUC for LHD was.744 (95% CI:.626–.863, p =.003) with the best cut-off of 5.85 and sensitivity of 80% (95% CI: 76.0–84.0) and specificity of 61.5% (95% CI: 58.4–64.6). The AUC for Maf was.707 with optimal cut-off value 12.65 and sensitivity of 83.3% (95% CI: 79.1–87.5) and specificity of 60.0% (95% CI: 57.0–63.0). Furthermore, LHD performance was not affected by vitamin B12 status. Conclusion: LHD and Maf are useful for iron deficiency diagnosis in stable COPD patients. LHD was shown to be resistant to vitamin B12 deficiency, which is of substantial importance in specific patient subpopulations. Both parameters are not technology-dependant and do not require additional sample and/or reagent volume, which makes them cost-effective and convenient for everyday use. © 2023 John Wiley & Sons Ltd.

Introduction Pulmonary embolism (PE) is a serious complication of deep venous thrombosis, with a significant morbidity and mortality. More often, PE complicates the course of the nephrotic syndrome (NS), in particular when the disease is active, but it may occur as the first sign of illness when the diagnosis of the NS is being delayed as a result. Membranous nephropathy is, generally speaking, the most commonly reported glomerulonephritis associated with the increased risk of thrombosis. Case outline This report summarizes our experience with three young male patients (a 26-year-old, a 22-year-old, and a 45-year-old), in which PE was the first presenting feature of the NS. All of them were admitted to the hospital experiencing chest pains, dry cough, and shortness of breath. One of them had high temperature and the other two swelling of the lower parts of legs. Computed tomography of the thorax showed pulmonary artery thrombosis in all three patients. Diagnosis of the NS was confirmed by laboratory analysis, while renal biopsy showed membranous nephropathy. The treatment was based on the pulse of methylprednisolone (1.5 g over a period of three days), with alternating therapy of oral corticosteroids and cyclophosphamide on a monthly basis during six months. After six months, two patients reached incomplete remission, while the third one still has the NS and normal renal function. Conclusion Not so rare occurrence of thromboembolic events in the NS suggests that one should always suspect the NS in all patients with deep venous thrombosis or PE. © 2017, Serbia Medical Society. All rights reserved.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Background/Aim. Corticosteroids are the most frequently prescribed anti-inflammatory treatment in asthma. A purpose of this study was to compare the spirometric parameters as a response to inhaled fluticasone propionate (FP) treatment in children with asthma, exposed and nonexposed to environmental tobacco smoke (ETS). Methods. The study included 527 children aged between 1 and 16 years with persistent asthma divided into the groups of ETS exposed (ETSE, n = 337) and ETS free (ETSF, n = 190) children. Spirometry was performed before (1st set of results) and after 6 months of FP treatment (2nd set of results). Good lung function (GLF) was defined as forced expiratory volume in one second (FEV1) ≥ 85%, and “poor lung func-tion” (PLF) as FEV1 < 85%. Results. Among the ETSE children, 208 had one smoking parent, 129 had two, 228 had smoking mothers and 238 smoking fathers. The ETSE children received a higher FP dose (p < 0.0001) which was increased with the increase of the number of smokers in the family. The ETSE children had significantly lower lung function both in the 1st and 2nd sets of tests compared to the ETSF children (p < 0.05). After the FP treatment, both groups improved all spirometric parameters (p < 0.001). In the 2nd set of the spirometric tests, the children of smoking mothers had lower spirometry values compared to the children of smoking fathers (p < 0.05). The proportion of the children improving from the PLF to GLF after 6 months of FP was much higher among the ETSF than the ETSE children (p < 0.05). Conclusions. The ETSE children had lower spirometric values before FP. After 6-months of the FP treatment children in both groups improved the spirometric values, but the improvement was higher in the ETSF children. © 2019, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Asthma is the most common chronic disease in children and adolescents and a serious global health problem, thus severely affecting the health related quality of life (HRQL). This study was aimed at exploring the potential role of the Serbian, self administered version of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) in the routine clinical evaluation of children suffering from bronchial asthma. One hundred Serbian children and adolescents (62 males and 38 females), aged 7 to 17 years, affected by allergic asthma, were enrolled. Each patient was evaluated once, and asthma control and severity were assessed, spirometry was performed, FeNO measurements were performed and the patients completed the self-administered version of the PAQLQ. PAQLQ differed according to asthma severity, NO variation and Asthma Control Test (ACT) score. No correlations were found between the questionnaire's score and FEV1 percent of predicted. The Serbian version of the PAQLQ is a feasible aid to clinical measurements and used in routine practice gives a good insight into asthma control and severity.

Background/Aim. The Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a simple and reliable tool designed to measure overall COPD related health status and complement physician assessment in routine clinical practice. Objective of this study was to evaluate the validity of the Serbian version of CAT. Methods. Study included 140 outpatients in the stable COPD, recruited from two centres: Clinic for Pulmonology, Clinical Center of Serbia, Belgrade, and Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica. All patients completed pulmonary function testing - spirometry, the CAT and the modified Medical Research Council (mMRC) dyspnea scale at baseline visit. The CAT test-retest reliability was tested in 20 patients by the same investigator (physician). Results. We demonstrated that Serbian version of CAT had high internal consistency with Cronbach's alpha 0.88. Test-retest analysis showed good correlation between CAT scores in two time points (Spearman's ρ = 0.681, p < 0.01). In our study the CAT correlated moderately to mMRC scale (ρ = +0.57), weakly to FEV1 (ρ -0.214), was positively related to number of exacerbations, but did not showed exact regularity with change in the Global Initiative for Chronic Obstructive lung disease (GOLD) stage. Conclusion. The Serbian version of CAT is a reliable, simple and easy-to-use tool that can be used in everyday clinical practice to assess the health status of COPD patients in Serbia. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. Asthma still remains poorly controlled in the majority of patients. The Asthma Control Test (ACT) is a short and useful patient-administered questionnaire for identification of patients with poor asthma control in clinical settings. The aim of this study was to validate a Serbian version of the ACT in the adults with asthma. Methods. A total of 250 consecutive adult asthmatic patients were recruited in a prospective observational study. The exclusion criteria were chronic respiratory disease and acute respiratory tract infection in preceding 4 weeks. Results. The spirometry and ACT questionnaire were performed on the baseline visit and 6 months later. The ACT test was completed by 98.8% of patients with the mean time of completion of 4.5 minutes. The correlation of ACT score and lung function parameters (forced expiratory volume in 1 second - FEV1 and forced vital capacity - FVC) was significant (p = 0.016 and p = 0.002, respectively). A change in the ACT scores between baseline and 6- months visit was not associated with a change in FVC and FEV1. The ACT score had excellent diagnostic accuracy according to the physicians asthma control classification and even outstanding accuracy according to the patients' classification. Conclusion. The results of this study confirm the reliability, validity and accuracy of Serbian version of the ACT, contributing to established value of original ACT test and with consistent findings as the previously reported validity of ACT in other languages. Therefore, it should be utilized more in everyday clinical practice as a useful and reliable tool of asthma control assessment. © 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Scleredema adultorum (SA) is a rare sclerotic disorder characterized by non-pitting induration of the neck with acral progression, sparing hands and feet. We report on a 57-year-old male with severe SA associated with paraproteinemia, treated with methotrexate. Such widespread skin thickening followed by severe movement restriction and inability to function on daily basis, as in our patient, has never been described. Severe osteoarthritis and finding of HLA-B39 allele in association with SA has not been previously described either. To the best of our knowledge, up to 40 patients with SA associated with paraproteinemia has been reported so far, and currently, there is no established effective treatment protocol. In our patient, low-dose methotrexate resulted in stiffness reduction, increased motility of the trunk and extremities, and ability to function on daily basis. We believe that any information about treatment outcome in SA patients should be disseminated in order to establish consensual treatment protocol for this rare disease.