Ljudmila Nagorni-Obradovic

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.

Matrix metalloproteinases gene variants in idiopathic disseminated bronchiectasis.

Background The excess of matrix metalloproteinases (MMPs) might be associated with the airways destruction or dilatation in bronchiectasis. The functional promoter polymorphisms of MMP1 and MMP9 genes, involved in the extracellular matrix remodeling, might increase the expression of MMPs leading to the development of bronchiectasis. Methods Detection of MMP1 G-1607GG and MMP9 C-1562T gene variants was performed on 37 patients with idiopathic disseminated bronchiectasis and 102 control subjects. We also described a novel method for simple and rapid detection of MMP1 G-1607GG polymorphism. Results The frequency of -1607GG allele was significantly higher in the group of patients than in control subjects (P = 0.014). The heterozygote genotype showed association with bronchiectasis (odds ratio, 5.3; 95% confidence intervals, 1.4-20.0). The association was even stronger in homozygotes for -1607GG allele (odds ration, 8.7; 95% confidence intervals, 1.9-41.0). The allelic and genotype frequencies of MMP9 C-1562T variant did not show significant differences between the groups. Conclusions This is the first report concerning a role of MMP1 G-1607GG and MMP9 C-1562T variants in pathogenesis of idiopathic disseminated bronchiectasis. The results of our study revealed the association of -1607GG allele and the lack of association of MMP9 C-1562T variant with the disease.

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.

Asthma and chronic bronchitis symptoms among adult population of Belgrade

INTRODUCTION Over the last three decades the prevalence of respiratory diseases has been increasing worldwide thus increasing economic burden on the healthcare system. Recent studies have shown that the prevalence of asthma in West European countries ranges from 6-9%, while of chronic obstructive pulmonary diseases (COPD) is 8.0% worldwide. OBJECTIVE The aim of the study was to estimate the prevalence of respiratory symptoms and smoking habits, and to assess the prevalence of asthma and chronic bronchitis among adults in Belgrade, Serbia. METHODS To collect data we used a questionnaire based on the European Community Respiratory Health Survey (ECRHS) protocol, which was mailed to 10,208 randomly selected subjects. RESULTS There were 58.3% of responders to our questionnaire. We noted a higher prevalence of respiratory symptoms in subjects who responded promptly. The majority of the respondents were current or former smokers (37.5% and 17.5% respectively) and 79.9% of them reported respiratory symptoms. The most frequent symptoms were longstanding cough (32.2%), sputum production (30.4%) and wheezing (30.3%). Asthma attacks were reported in 4.4% of cases and 5.6% of subjects were using asthma medications. The prevalence of respiratory symptoms increased with age. Women reported coughing, attacks of breathlessness and coughing, chest tightness by night, allergic rhinitis and chronic coughing, more frequently than men. Productive cough was more frequent in men. The prevalence of almost all symptoms was higher in smokers compared to nonsmokers. CONCLUSION In Serbia there is a high prevalence of respiratory symptoms, asthma and chronic bronchitis smoking addiction.

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population / Udruženost Funkcionalnih Varijanti Gena Faze I I Ii Sa Hroničnom Opstruktivnom Bolešću Pluća U Srpskoj Populaciji

Summary 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. Kratok sadržaj Uvod: Hronična opstruktivna bolest pluća (HOBP) jeste složeno oboljenje koje karakteriše povišen oksidativni stres. Funkcionalne varijante gena faze I i II ksenobiotičkog meta- bolizma mogu uticati na ravnotežu oksidanti-antioksidanti i mogu dovesti do razvoja HOBR Cilj ove studije je bio ispi- tivanje uloge funkcionalnih genskih varijanti u genima za citohrom P450 (CYP), glutation S-transferazu (GST) i mi- krozomalnu epoksidnu hidrolazu (mEH) u patogenezi HOBP u srpskoj populaciji. Metode: U ovoj studiji analizirane su genske varijante CYP1A1 *W*2A, CYP2E1 *W*5B, GSTM1 null, GSTT1 null, GSTP1 lle105Val, mEH Tyr113His i mEH His139Arg u grupi obolelih od HOBP koja je obuhvatala 122 ispita- nika i kontrolnoj grupi koja je obuhvatala 100 ispitanika sa normalnom funkcijom pluća. Rezultati: Dobijeni rezultati su pokazali da je GSTM1 null varijanta statistički značajno povišena u grupi obolelih od НОВР u poređenju sa kontrolnom grupom (61,5% i 47,0%; OR=1,80; p=0,042). Takođe, uočena je značajna razlika u zastupljenosti kombinacije genotipova GSTM1 null i GSTP1 105Val/(Val) (38,5% i 24,0%; OR=1,98; p=0,029), kao i kombinacije СУР1А1 *1A/*2A, GSTM1 null i mEH 113His/(His) (7,4% i 1,0%; OR=7,88; p=0,025). Zaključak: Ovo su prvi podaci o ulozi genskih varijanti gena faze I i II u patogenezi HOBP u srpskoj populaciji. Rezultati dobij|eni u ovoj studiji otvaraju mogućnostza detaljniju ana- lizu uloge genetičkih faktora u HOBP na većim grupama ispitanika. Pored toga, podaci dobijeni u našoj studiji po- tvrđuju važnost genetičkih determinanti povezanih sa HOBP u prethodnim studijama, ali takođe otkrivaju nove genetičke faktore, koji nisu objavljeni do sada.

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.

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 (Cohens 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.

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.

Lifestyle and perceived health in subjects with chronic bronchitis or emphysema: a cross-sectional study

BackgroundThe study aim was to compare lifestyle behaviors, body mass index (BMI) and perceived health in subjects with and without chronic bronchitis or emphysema, and to explore if these comparisons differed between demographic subgroups.MethodsA stratified two-stage sample of the population of Serbia was used; 14.522 adults aged ≥20 years were interviewed.ResultsCompared with controls, respondents with chronic bronchitis or emphysema reported a 23% increased likelihood of eating fresh vegetables every day (CI 1.02-1.48), 58% increased likelihood of currently smoking (CI 1.32-1.88) and more likely to perceive their health as very bad or bad (OR 4.67, CI 3.64-5.98). After stratification for sex, education, and type of settlement, smoking was significantly associated with chronic bronchitis or emphysema in all subgroups except males. The increased likelihood of very bad or bad perceived health in respondents with chronic bronchitis or emphysema was significant in all subgroups, and was highest for respondents ≤65 years of age (adjusted OR 6.51; CI 4.87-8.72) and lowest for respondents >65 years of age (adjusted OR 3.25; CI 2.12-4.97).ConclusionEfforts to enhance perceived health and healthy lifestyle behaviors in subjects with chronic bronchitis or emphysema are necessary. Special attention should be paid to smoking cessation in almost all demographic subgroups.