Ivana Stankovic

Frequency and significance of unrecognized chronic obstructive pulmonary disease in elderly patients with stable heart failure

Background and aims: Due to prolonged life-spans and modern therapeutic approaches, there has been an increase in the number of patients aged ≥65 years with chronic heart failure (CHF). The duration and quality of life in elderly patients with CHF also depend on accompanying diseases. Although frequency of chronic obstructive pulmonary disease (COPD) in patients with CHF is about 30%, it is hard to find similar data in the elderly population. COPD is defined as a spirometrically assessed ratio of a post-dilatory forced expiratory volume in the first second, divided by forced vital capacity (FEV1/FVC) <70%. The aims of our study were to assess the prevalence of previously undiagnosed COPD in outpatients (≥65 yrs) with stable CHF and to determine the effect of the combination of COPD and CHF on patients’ functional capacity as measured by a 6-minute walking test. Methods and Results: Of the 174 study patients, 126 (72.4%) were men. In 48 patients (27.6%) we found previously unrecognized COPD. They were significantly older (75.6±5.8 vs 73±4.5 years, p<0.01) and more frequently had abdominal obesity and a greater waist circumference (98.8±10.2 vs 94.9±9.1 cm, p<0.05). Patients with COPD had significantly shorter 6-min walking distance (275.5±112.9 vs 291.3±96.7 m, p<0.05). Only patient’s age had a positive prognostic association with unrecognized COPD (OR=1.16; 95% CI 1.01–1.34, p<0.01). Patients with COPD showed a significant correlation between actual/predicted FEV1 and the 6-min walking distance (r=0.39, p<0.01). Conclusions: We found a high prevalence of unrecognized COPD in elderly patients with CHF and central obesity. Chronic obstructive pulmonary disease influenced functional capacity in CHF patients, as determined by the 6-minute walking test. Closer co-operation between pulmonologists and cardiologists is necessary to optimize management of this large proportion of CHF patients.

Peak Expiratory Flow–Guided Self-Management Treatment of Asthma in Serbia

The aims of this study were to compare the efficacy of 1-year peak expiratory flow (PEF)–based self-management of asthma against conventional treatment and to analyze the long-term effectiveness of self-management. Eighty adult patients with persistent asthma (group B). After 1 year, significant improvement was noted in markers of asthma severity in group A but there were no changes in group B. After 6 years of the self-management program, asthma morbidity and emergency use of health services were reduced. These results show short-term and long-term effectiveness of a PEF-based self-management program in persistent asthma.

Vitamin D Receptor Gene Polymorphisms in Serbian Patients With Bronchial Asthma: A Case-Control Study

Vitamin D and single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene are potentially involved in the pathogenesis of bronchial asthma (BA); however, precise mechanisms by which vitamin D reduces the inflammation and the role of VDR SNPs in BA are not completely understood. The aim of this study was to examine the possible associations of FokI, BsmI, ApaI, and TaqI SNPs with BA. A total of 168 subjects were screened for VDR SNPs using polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) method. The obtained results showed statistically significant differences in the distribution of FokI genotypes (df = 2; P = 0.008) and alleles (P = 0.002; OR = 0.446; 95%CI = 0.264–0.752) between patients and controls. Distributions of BsmI, ApaI, and TaqI genotypes and alleles did not show statistical differences. BsmI, ApaI, and TaqI SNPs are in linkage disequilibrium (LD) in the whole studied group, as well as in BA patients and controls. The strongest LD was observed between BsmI and TaqI (r2 = 0.69 for all subjects in the study; r2 = 0.75 in BA; r2 = 0.64 in controls), while lower values of LD were observed for BsmI and ApaI, and ApaI and TaqI SNPs. This is the first study that examined the association of VDR SNPs (FokI, BsmI, ApaI, and TaqI) in Serbian patients with BA indicating protective effect of FF genotype and F allele of FokI SNP on BA development. J. Cell. Biochem. 118: 3986–3992, 2017.

Gene Polymorphisms of Tumor Necrosis Factor Alpha and Antioxidant Enzymes in Bronchial Asthma

BACKGROUND Bronchial asthma is an inflammatory disease resulting from a combination of genetic and environmental factors. Single nucleotide polymorphisms in the regulatory regions of cytokine and antioxidant enzyme genes may affect cytokine production and enzyme activity, and thus play a contributory role in asthma pathogenesis. OBJECTIVES The aim of this study was to examine the association of manganese superoxide dismutase (MnSOD) Ala16Val, catalase (CAT) A-21T and tumor necrosis factor alpha (TNF-α) G-308A polymorphisms with bronchial asthma. MATERIAL AND METHODS A total of 79 patients with asthma and 95 healthy controls were screened for MnSOD Ala16Val, CAT A-21T and TNF-α G-308A polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS The results obtained showed significantly higher prevalence of the MnSOD ValVal genotype (χ2=14.463, df=2, p=0.001) and MnSOD 16Val allele (χ2=12.862, p=0.026, OR=0.451, 95% CI=0.291-0.699) in patients with asthma compared to controls. The genotype and allele frequencies distribution of CAT A-21T and TNF-α G-308A gene polymorphisms did not show differences between patients and controls. CONCLUSIONS Our results show an association of MnSOD Ala16Val genetic polymorphism with asthma in a Serbian population and suggest a protective role of the MnSOD 16Ala allele.

Chronic Airflow Obstruction Syndrome Due to Pulmonary Tuberculosis Treated with Directly Observed Therapy – a Serious Changes in Lung Function

UNLABELLED The origin of Chronic airflow obstruction (CAO) syndrome in active Tuberculosis (TB), despite significant similarities with chronic obstructive pulmonary disease (COPD), still remains unknown. The aim of the study was to examine the potential causes and risks for the development of CAO syndrome in new cases of pulmonary TB. DESIGN Prospective, nest case-control study. PATIENTS 40 patients with newly detected cavitary pulmonary TB and initial normal respiratory function, diagnosed and treated according to DOTS strategy. MEASUREMENTS AND RESULTS The average values of Sniders radiological score during TB treatment were significantly reduced (p < 0.001), as well as average values of non-specific systemic serum markers of inflammation. The average values of FEV1 (%), both before, during and at the end of completion of TB treatment were significantly decreased (p < 0.05;). Linear regression analysis confirmed a statistically significant association between changes in the values of FEV1 (%), resulting in TB treatment completion, and the value of Sniders radiological score and the sputum culture conversion rate. From the initial findings of normal pulmonary ventilation tests, upon the completion of TB treatment 35.0% of observed patients developed the CAO syndrome. Logistic regression analysis confirmed a positive familiar burden for COPD, Sniders radiological score at the beginning of TB treatment and sputum conversion rate on culture, as statistically significant predictors, while multivariate logistic regression analysis confirmed Sniders radiological score at the beginning of TB treatment and sputum conversion rate on culture as most significant risk factors for CAO syndrome occurrence and development. CONCLUSION The CAO syndrome is often a consequence and significant functional impairment of the respiratory system, during the reparative processes in active TB, even in the absence of risk factors for COPD. Only microbiological cure of TB patients with underlying risks for disorders of lung function, is not sufficient and effective approach for prevention of their further potential health deterioration.

Is There Any Point in a Corticosteroid Treatment of Intermittent Asthma

International guidelines advocate the early introduction of inhaled corticosteroids (ICS) in all types of persistent asthma. Our study was undertaken to assess the effects of ICS on bronchial hyperresponsiveness (BHR) as a hallmark of inflammation, and to assess the symptoms, the use of rescue medications, and the parameters of lung function in patients with mild intermittent asthma. The patients with intermittent asthma (n = 85) were randomly allocated to a treatment with ICS, beclomethasone dipropionate 250 μg/day and short-acting β2 agonists salbutamol as needed (Group A, n = 45) or to a treatment with only short-acting β2 agonists as needed (Group B, n = 40) during the 6-month treatment period. At the end of the study, in Group A, we found a statistically significant decrease of BHR (PD20 0.98 vs. 2.07) (p < 0.001), diurnal peak expiratory flow (PEF) variability (17.9 vs. 13.8) (p < 0.001), symptom scores (0.63 vs. 0.30) (p < 0.001), and used rescue medication (p < 0.001), while the parameters of lung function remained unchanged except for forced expiratory volume in 1 sec (FEV1), which had a statistically significant increase (3.58 vs. 3.66) (p < 0.001). In Group B, there was a statistically significant decrease of lung function parameters FEV1 (3.80 vs. 3.71) (p < 0.001), forced vital capacity (FVC) (4.43 vs. 4.37) (p < 0.001), FEV1/FVC (88.2 vs. 85.3) (p < 0.05), PEF (8.05 vs. 7.51) (p < 0.01), PEF variability (17.85 vs. 18.33) (p < 0.001), increased BHR (PD20 1.04 vs. 0.62) (p < 0.05), and symptom scores (0.46 vs. 0.62) (p < 0.01), as well as the use of rescue medication during the day (p < 0.001). Early introduction of low doses of ICS may be more beneficial than β2 agonists alone in patients with intermittent asthma.

Rare congenital hearth disease as a cause of tuberculosis activation

INTRODUCTION Patients with congenital cyanotic heart defects and the left-to-right shunt are at a three times higher risk of getting tuberculosis than acyanotic ones. No TB cases have been recorded in adult patients with the right-to-left shunt having cyanosis since their birth. CASE REPORT A 34-year-old man was referred to our Clinic with the discomforts such as chronic cough, hemoptysis and insomnia. At the admission he was pale, cyanotic, with a partial manifest respiratory insufficiency and characteristic TB pulmonary lesions detected by x-rays and tomography. After the sputum positive TB recidivism had been diagnosed, the antituberculotics treatment was introduced resulting in the successful smear and culture conversion and radiological regression of pulmonary lesions, but associated with non-explicable deterioration of cyanosis and chronic respiratory insufficiency until Doppler-echocardiographic examination verified the presence of tetralogy of Fallot. CONCLUSION Congenital cyanotic heart defects are extremely rare in adults. Nevertheless, it is necessary to maintain a very high level of clinical suspicion regarding TB activation even in the cases of defects with the right-to-left shunt.

The impact of inhaled corticosteroids on cough and bronchial hyperreactivity in cough variant asthma

INTRODUCTION Classic asthma is characterized by cough, wheezing and dyspnea. Cough, however, may be the sole presenting symptom of asthma and this type of asthma is known as cough-variant asthma. The therapeutic approach to cough variant asthma is similar to that of the typical form of asthma. A diagnosis of cough-variant asthma is made when a chronic cough is associated with airway hyperresponsiveness and a favorable response to asthma therapy in the absence of other discernible cause. The aims of this study were to analyse the influence of inhaled corticosteroids on cough and bronchial hyperresponsiveness. MATERIAL AND METHODS The study included 55 patients with cough as the sole presenting symptom. 40 patients (Group A) were treated with inhaled corticosteroids and beta2 agonists for eight weeks while 15 patients (Group B) were treated only with oral beta2 agonists. The nonspecific bronchoprovocative test with histamine was performed on all the patients before the treatment and after the examination and there was established the provocative dose of histamine causing the 20% fall in FEVI (PD20). RESULTS At the end of the study in Group A we found a statistically significant decrease of PD20 0.98 +/- 0.86 vs. 1.58 +/- 1.06 (p < 0.005), while in Group B there were no significant changes. In 90% of the patients treated with inhaled corticosteroids the cough was completely relieved while in 80% of the patients treated with only beta2 agonists the cough has remained unchanged. CONCLUSION Inhaled corticosteroids are choice drugs for the treatment of cough-variant asthma because they relieve cough and decrease bronchial hyperresponsiveness, thus ultimately reducing the risk of classic asthma.

Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis – limitations for the underlying COPD detection

Background During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. Purpose The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Patients and methods Prospective, nest case–control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. Results From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%–20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%–20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%–0.700% for 95% CI; P=0.047), leukocyte count (0.020%–1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%–0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01–1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02–1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. Conclusion AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration.

C-reactive protein levels of pleural fluid of parapneumonic effusions and its role in prognosis

Abstract The purpose of this study was to evaluate levels of C-reactive protein (CRPpf), glucose (Gpf) and lactic dehydrogenase (LDH) of pleural effusions in patients with empyema (E) (n=18), complicated parapneumonic effusions (CPPE) (n=27) and uncomplicated parapneumonic effusions (UPPEs) (n=26). The control group (n=38) was comprised of patients with malignant effusions. We determined the correlation with the values of CRPpf with LDHpf and Gpf, as well as the presence of PPE complications, which determine if there is a relationship between the values of CRPpf in research groups and PPE complications. Data were analyzed by ANOVA, Mann-Whitney U-test and Spearman’s correlation analysis. The levels of CRPpf in patients with E were 76.44±30.55, in patients with CPPE 46.42±22.1, in patients with UPPE 23.56±19.38 and lower in the malignant groups 17.27±12.9. The area under the curve for distinguishing CPPE from E was 0.882±0.044 with 95% CI for CRP and sensitivity 0.667; specificity 0.962. As for the discrimination of CPPE vs. E, it was CRP≥65.5. The relationship between levels of CRPpf and pleural adhesions in patients with PPE was not found. We conclude that CRPpf levels can help in the diagnosis of PPE, but cannot predict long-term complications.