Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder with unexplained heritability. Interactions of genetic and environmental factors are thought to be crucial in COPD. So, we aim to examine interactions of the endothelial nitric oxide synthase (eNOS) and angiotensin converting enzyme (ACE) genes and cigarette smoking in COPD. Methods: The eNOS G 894T and ACE ID variants were analyzed in 122 COPD patients and 200 controls from Serbia. The effect of the variants on COPD was assessed by logistic regression. Interactions between eNOS, ACE and cigarette smoking in COPD were evaluated using a case-control model. Interaction between the genes was analyzed in silico. Results: No effect of the eNOS G 894T and ACE ID variants on COPD was found in our study. Gene-gene interaction between the eN OS T T and A CE D was identified (p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environment interactions between the eNOS T and cigarette smoking (p=0.013), and the ACE II and cigarette smoking (p=0.009) were detected in COPD in our study. Conclusions: This is the first research to reveal interactions of the eNOS and ACE genes and cigarette smoking in COPD progressing our understanding of COPD heritability and contributing to the development of appropriate treatments.

Low-Cost Genetic and Clinical Predictors of Response and Toxicity of Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer.

Background: This study aimed to evaluate for the first time whether certain genetic and clinical factors could serve as minimally invasive predictors of survival and toxicity to platinum-based chemotherapy in advanced lung adenocarcinoma. Methods: The study included 121 advanced lung adenocarcinoma patients treated with platinum-based dublets until progression or unacceptable toxicity. Response was evaluated using standard radiological methods and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Genotyping was performed using PCR-RFLP. Statistical significance was set at P < .05. Results: No significant influence of the examined polymorphisms on the occurrence of high-grade toxicity was detected. However, TP53 72Pro allele carriers were more prone to nausea (P = .037) and thrombocytopenia (P = .051). Anemia and neuropathy occurred more frequently in XRCC1 399Arg allele carriers (Pearson χ2 test, P = .025 and P = .004 respectively). RAD51 135CC carriers were significantly more prone to neutropenia (P = .027). Conclusions: A set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.

Reliability and Validity of the Pittsburgh Sleep Quality Index-Serbian Translation.

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.

Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians.

Chronic obstructive pulmonary disease (COPD) is a complex disorder influenced by multiple genetic and environmental factors, as well as their interactions. Since elevated oxidative stress and protease activity characterize the pathogenesis of COPD, variants of genes that can affect these processes have been commonly studied in COPD. However, interactions among genes that can influence oxidative stress and protease activity remain poorly investigated in COPD. The aim of this study was to look into the role of functional variants in matrix metalloproteinases (MMPs) 1, 9, and 12 in the occurrence and/or modulation of COPD, and to analyze their interactions with glutathione S-transferases (GSTs) M1, T1, and P1 in the pathogenesis of COPD in Serbians. The MMP1 rs1799750 G > GG, MMP9 rs3918242 C > T, and MMP12 rs2276109 A > G variants were analyzed by direct detection methods. Gene-gene interactions between variants in MMPs and GSTs were assessed using a case-control model. Our results showed association of the MMP1 GG/GG genotype with COPD (p = 0.036, OR = 2.50). Gene-gene interactions between the GSTM1 null and MMP1 GG (p = 0.028, OR = 2.99) and the GSTM1 null and MMP12 AA variants (p = 0.015, OR = 3.82) were found to significantly increase the risk of COPD occurrence. Furthermore, the MMP12 G variant was found to modify the age of COPD onset (p = 0.025, OR = 3.30), while interaction between the GSTM1 null and MMP9 T variants was found to modify the severity of disease (p = 0.019, OR = 4.83). To our best knowledge, this is the first study revealing several gene-gene interactions affecting oxidative stress and protease activity in the pathogenesis of COPD.

Screening commercial drivers for obstructive sleep apnea: Validation of STOP-Bang questionnaire.

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. Int J Occup Med Environ Health 2016;30(5):751-761.

Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults.

The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.

Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease.

The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. © 2016 Wiley Periodicals, Inc.

Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency.

Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.

Bullous lung diseases as a risk factor for lung cancer: A case report.

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.

Screening commercial drivers for obstructive sleep apnea: translation and validation of Serbian version of Berlin Questionnaire.

PURPOSE: Obstructive sleep apnea (OSA) can lead to severe health consequences. Drivers of motor vehicles with untreated or undiagnosed OSA have a greater risk of traffic accidents. Use of self-reported questionnaires is the first step in OSA diagnosis. The main aim of this study was to perform the translation and validation of Berlin Questionnaire in a sample of commercial drivers. METHODS: After formal translation, validation was performed on a sample of commercial drivers and included evaluation of internal consistency, test-retest reliability, construct and criterion validity. Full-night attended polysomnography or cardiorespiratory polygraphy was used for OSA diagnosis. RESULTS: One hundred male participants, 24-62 years old, were included. Berlin Questionnaire classified 35 % subjects as potential OSA patients. Polysomnography confirmed OSA in 58 % of the subjects. Berlin Questionnaire showed good internal consistency (Cronbach's alpha 0.82-first category, 0.73-0.95-second category). Test-retest reliability (Cohen's kappa 0.78) was adequate. Berlin score was significantly correlated with OSA category and apnea-hypopnea index (AHI). Sensitivity of Berlin Questionnaire was from 50.9 (AHI ≥ 5) to 75 % (AHI ≥ 30), while specificity ranged from 86 to 70.5 %. CONCLUSIONS: Berlin Questionnaire (Serbian version) showed good measurement properties, creating basis for further research of its usefulness as OSA screening tool in populations of interest.

Assessment of health-related quality of life in end-stage chronic obstructive pulmonary disease and non-small-cell lung cancer patients in Serbia.

OBJECTIVE: Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. METHOD: This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. RESULTS: The COPD group scored significantly lower compared to NSCLC patients in all SF-36 domains except for bodily pain. Additionally, a significantly higher level of depressive symptoms was observed in COPD patients. A worse physical QoL for COPD patients was independently associated with a longer duration of unemployment, a lack of wage earning, lower Karnofsky Performance Status (KPS) scores, and higher levels of depression. A worse mental QoL for COPD patients was related to a longer duration of disease, poorer KPS scores, and higher BDI scores. The independent variables significantly associated with worse physical and mental QoL of NSCLC patients were lower KPS and higher BDI scores. SIGNIFICANCE OF RESULTS: A worse QoL, a significantly higher level of depressive symptoms, and adverse socioeconomic status in the COPD group imposes the need for development of more intensive psychosocial and community support for COPD patients during implementation of palliative care.

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population.

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.

Questionable Reliability of Homocysteine as the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease.

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 (χ̄±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 cutoff 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.

Illness perception in tuberculosis by implementation of the Brief Illness Perception Questionnaire - a TBNET study.

How patients relate to the experience of their illness has a direct impact over their behavior. We aimed to assess illness perception in patients with pulmonary tuberculosis (TB) by means of the Brief Illness Perception Questionnaire (BIPQ) in correlation with patients' demographic features and clinical TB score. Our observational questionnaire based study included series of consecutive TB patients enrolled in several countries from October 2008 to January 2011 with 167 valid questionnaires analyzed. Each BIPQ item assessed one dimension of illness perceptions like the consequences, timeline, personal control, treatment control, identity, coherence, emotional representation and concern. An open question referred to the main causes of TB in each patient's opinion. The over-all BIPQ score (36.25 ± 11.054) was in concordance with the clinical TB score (p ≤ 0.001). TB patients believed in the treatment (the highest item-related score for treatment control) but were unsure about the illness identity. Illness understanding and the clinical TB score were negatively correlated (p < 0.01). Only 25% of the participants stated bacteria or TB contact as the first ranked cause of the illness. For routine clinical practice implementation of the BIPQ is convenient for obtaining fast and easy assessment of illness perception with potential utility in intervention design. This time saving effective personalized approach may improve communication with TB patients and contribute to better behavioral strategies in disease control.

Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?

INTRODUCTION: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. SUBJECTS AND METHODS: 50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. RESULTS: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). CONCLUSION: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.

The prevalence of COPD co-morbidities in Serbia: results of a national survey.

BACKGROUND: Research studies have found different prevalence rates for co-morbidities in patients with chronic obstructive pulmonary disease (COPD). AIMS: The aim of our study was to investigate the prevalence of co-morbidities as well as functional limitations in subjects with COPD. METHODS: The study was based on a nationally representative sample of the population of Serbia. Information on the health of the population was obtained from interviews and anthropometric measurements. In this study we analysed a total of 10,013 respondents aged 40 years or older. There were 653 subjects with COPD and 9,360 respondents without COPD. RESULTS: Out of the 10,013 respondents, 5,377 were aged 40-59 years and 4,636 were 60 years or older. The prevalence of COPD was 5.0% in respondents aged 40-59 years and 8.3% in those aged 60 years or older; the total prevalence was 6.5%. The most prevalent co-morbidities among respondents with COPD were hypertension (54.5%) and dyslipidaemia (26.5%). The prevalence of all analysed co-morbidities was higher in respondents with COPD and the difference was highly statistically significant, except for stroke and malignancies, for which the difference was significant. Analysis showed that respondents with COPD had a higher prevalence of all analysed clinical factors (dizziness, obesity, anaemia and frailty) and functional impairments (mobility and hearing and visual impairment) compared with respondents without COPD. For those aged 40-59 years the difference was highest for mobility difficulty (four times higher prevalence in COPD patients) and anaemia (three times higher in COPD patients). CONCLUSION: Our analysis showed that the most prevalent co-morbidities in COPD were hypertension, dyslipidaemia, chronic renal disease and anxiety/depression. The finding suggests that health professionals should actively assess co-morbidities in patients with COPD.

Alpha-1-antitrypsin deficiency in Serbian adults with lung diseases.

AIM: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. METHODS: The study included the adults with chronic obstructive pulmonary disease (COPD) (n=348), asthma (n=71), and bronchiectasis (n=35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. RESULTS: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1:5519, 1:38, and 1:5519). CONCLUSION: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.

The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions.

PURPOSE: The aim of our study was to assess diagnostic accuracy of Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary lesions that appeared ambiguous on computed tomography (CT). MATERIAL AND METHODS: Forty-nine consecutive patients (37 men and 12 women; mean age, 60 ± 11 years) with 60 pulmonary lesions on chest radiography and CT were referred for nuclear imaging. They were prospectively allocated to undergo whole-body scintigraphy (WBS) and single photon emission computed tomography (SPECT) using either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging (23 patients, group 2). Histologic findings after tissue biopsy served as a gold standard for determining diagnostic accuracy of the 2 somatostatin analogs. Visual assessment was complemented by semiquantitative analysis based on target to background ratio. RESULTS: Among the 32 pulmonary lesions scanned with Tc-99m depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and 88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m-EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%, and accuracy 86%). Overall, target to background ratios were higher on SPECT than WBS but not significantly different between groups 1 and 2 (SPECT 2.72 ± 0.70 vs. 2.71 ± 0.50, WBS 1.61 ± 0.32 vs. 1.62 ± 0.28, respectively). CONCLUSION: This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC have similar diagnostic value for characterizing pulmonary lesions that appear ambiguous on CT.

Knowledge and awareness of tuberculosis among Roma population in Belgrade: a qualitative study.

BACKGROUND: Tuberculosis (TB) remains an important health problem in the Roma population in Serbia. Recent studies have highlighted the importance of increasing awareness of TB and reducing the associated stigmas to reduce the incidence of TB and enable earlier diagnosis and effective treatment. This study investigated the knowledge and beliefs about transmission, symptoms and treatment of TB as well as attitudes towards patients with TB among the Roma population in Belgrade. METHODS: The focus-group method was considered to be appropriate for investigating knowledge and beliefs about TB. A total of 24 Roma people aged 19-55 years participated in three focus-group discussions. RESULTS: All participants knew that TB was a pulmonary disease and could be contagious. Saliva was the most commonly mentioned mode of transmission. Some individuals thought, albeit hesitantly, that TB could be transmitted by shaking hands with an infected individual. Of factors contributing to TB, participants mentioned bad living conditions, low quality and lack of food, and stress. Participants quoted chest pain, cough, haemoptysis, loss of appetite, loss of weight, weakness and sweating as basic symptoms of TB. Participants believed that effective treatment should include resting, taking prescribed medicines, inhaling fresh air and eating "strong" food such as bacon and pork; these approaches were considered as important as taking antibiotics). In addition, participants mentioned that they use some folk medicines.Relatives and friends, and to a lesser extent television, were the main sources of information about TB. Participants most appreciate personal contact with doctors as a source of information. CONCLUSIONS: We concluded that participants were aware of the seriousness TB as well as some of the modes of transmission; however, they had some misconceptions. An important finding was the confidence in doctors expressed by the Roma people.