Browsing by Author "Nagorni-Obradović, Ljudmila (57189629141)"

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.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. Methods: The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 ∗1A/∗2A, CYP2E1 ∗1A/∗5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 ∗1A/∗2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025). Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far. © by Marija Stanković 2015.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. Methods: The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 ∗1A/∗2A, CYP2E1 ∗1A/∗5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 ∗1A/∗2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025). Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far. © by Marija Stanković 2015.

[No abstract available]

Introduction. A possible association between lung cancer and bullous lung disease has been suggested and recently supported by the results of genetic studies. Case report. A previously healthy 43-year-old man, smoker, was diagnosed with bullous lung disease at the age of 31 years. He was followed up for 12 years when lung cancer (adenocarcinoma) was found at the site. In the meantime, he was treated for recurrent respiratory infections. Conclusion. There is the need for active approach in following up the patients with pulmonary bulla for potential development of lung cancer. © 2016, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Introduction The systemic autoimmune diseases (SAD) can cause a variety of pulmonary and pleural abnormalities. The aim of this paper is to review clinical and radiological characteristics of a series of patients with a systemic autoimmune disease hospitalized at a tertiary level facility. Methods In this retrospective study, we reviewed the clinical and imaging findings in patients diagnosed with SAD at the Teaching Hospital of Pulmonology during a nine-year period. Results An 84-patient group (mean age of 53.8 years) consisted of 64 women and 20 men. Fifty-eight out of 84 patients suffered from collagen vascular disease (CVD) and 26/84 had systemic vasculitis. Fatigue was the dominant symptom (75.8% in CVD, and 69.2% in vasculitis). Cough, hemoptysis, and fever were more frequent in patients with vasculitis. Fibrosis was the most common radiological manifestation of CVD (26/58), followed by pleural effusion (18/58) and consolidation (10/58). Irregular opacities were dominant radiologic finding in vasculitis (10/26), followed by nodules (8/26). Histological confirmation of systemic autoimmune disease was obtained in 28.6% patients, in 58/84 patients the diagnosis was based on a positive serologic test and clinico-radiological manifestations, in two cases on clinical and radiological features according to defined criteria. Conclusion Pleuropulmonary manifestations of SAD are usually expressed in the sixth decade of life, predominantly in women. Clinical findings and positive serologic tests suggest diagnosis of SAD. Fibrosis is the most common radiologic pattern found in almost one half of the patients with CVD and irregular opacities are the most common findings in vasculitis. © 2020, Serbia Medical Society. All rights reserved.

[No abstract available]

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.

The aim of this study was translating and exploring psychometric properties of Serbian Pittsburgh Sleep Quality Index (PSQI) in a sample of “good” and “bad” sleepers suffering from depression or obstructive sleep apnea (OSA). Formal translation and validation were performed on a sample of healthy controls, patients with untreated OSA, and with diagnosed major depressive disorder with evaluation of internal consistency, test–retest reliability, and construct and criterion validity. Controls and OSA subgroups were recruited from a larger sample of commercial drivers. One hundred and forty subjects, 84.3% male, 22–67 years old, were included. OSA subgroup had 59 subjects and depression subgroup had 40 subjects (22 females). Mean ± SD total PSQI was 3.5 ± 2.2 in controls, 4.9 ± 3.6 in OSA subjects, and 9.0 ± 4.9 in patients with depression. Cronbach’s α for total PSQI was 0.791. Subscale scores were significantly correlated to global PSQI in all subgroups. Intraclass correlation coefficient for global PSQI was 0.997 (p <.001). Epworth Sleepiness Scale score was significantly correlated to global PSQI (ρ = 0.333, p <.001). Three subgroups differed significantly in total PSQI and PSQI ≥ 5, even after adjustments for age and gender (p <.001). OSA patients had higher mean PSQI than controls but not significantly (p =.272). PSQI-reported sleep latency did not correlate with PSG-measured sleep latency (r =.130, p =.204). Total PSQI was significantly correlated to OSA severity (ρ = 0.261, p <.05). Serbian PSQI showed good internal consistency, test–retest reproducibility, and adequate construct and criterion validity, which supports further exploration of its use as a sleep quality screening tool in different target populations. © 2016, © The Author(s) 2016.

Objectives: The main aim has been to examine psychometric properties of STOP-Bang (snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, male gender) scoring model (Serbian translation), an obstructive sleep apnea (OSA) screening tool, in a sample of commercial drivers. Material and Methods: After formal translation, validation was performed on a sample of bus and truck drivers evaluating test-retest reliability, construct and criterion validity. Overnight polysomnography or cardiorespiratory polygraphy were used for OSA diagnosis purposes. Results: One hundred male participants, 24–62 years old, were included. STOP-Bang classified 69% as potential OSA patients. Polysomnography identified OSA in 57% of the sample. Test-retest reliability (Cohen’s κ = 0.89) was adequate. STOP-Bang score was significantly correlated to apnea-hypopnea index (AHI) and OSA severity. Sensitivity was 100% for AHI ≥ 15, highest specificity was 53.5% (AHI ≥ 5). Conclusions: STOP-Bang showed good measurement properties, supporting its further use in OSA screening of commercial drivers.