Zorica Ciric

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

UNLABELLEDnThe 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.nnnDESIGNnProspective, nest case-control study.nnnPATIENTSn40 patients with newly detected cavitary pulmonary TB and initial normal respiratory function, diagnosed and treated according to DOTS strategy.nnnMEASUREMENTS AND RESULTSnThe 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.nnnCONCLUSIONnThe 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.

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.

Prognostic factors of mortality in elderly with community acquired pneumonia

BACKGROUND/AIMnCommunity acquired pneumonia in elderly has specific clinical aspect and higher mortality in relation to younger patients. According to specific pneumonia severity assessment on admission and its importance in proper prediction of clinical course and outcome, the aim of this study was defining prognostic factors of mortality.nnnMETHODSnThis study included 240 patients aged > or = 65 years with community acquired pneumonia. On admission, demographic characteristics, underlying diseases, physical symptoms and findings, laboratory values, chest radiography and oxygen blood saturation (SaO2) were analyzed. Multivariate analysis was used to identify characteristic prognostic factors which showed a statistical significance in relation to mortality.nnnRESULTSnAltered mental status, respiratory frequency > or = 23/min and the presence of bilateral pneumonic infiltrates were defined as the most important prognostic factors of mortality (p < 0.001). These factors displayed 57.89% sensitivity, 100% specificity and 93.33% accuracy.nnnCONCLUSIONnThe presence of identified characteristic prognostic factors on admission pointed out an adverse clinical course and outcome of community acquired pneumonia in elderly. Age and sex were not significantly associated with mortality.

In silico studies and the design of novel agents for the treatment of systemic tuberculosis

Abstract Tuberculosis (TB) is an ancient infectious disease, which re-emerged with the appearance of multidrug-resistant strains and acquired immune deficiency syndrome. Enoyl-acyl-carrier protein reductase (InhA) has emerged as a promising target for the development of anti-tuberculosis therapeutics. This study aims to develop quantitative structure-activity relationship (QSAR) models for a series of arylcarboxamides as InhA inhibitors. The QSAR models were calculated on the basis of optimal molecular descriptors based on the simplified molecular-input line-entry system (SMILES) notation with the Monte Carlo method as a model developer. The molecular docking study was used for the final assessment of the developed QSAR model and designed novel inhibitors. Methods used for the validation indicated that the predictability of the developed model was good. Structural indicators defined as molecular fragments responsible for increases and decreases of the studied activity were defined. The computer-aided design of new compounds as potential InhA inhibitors was presented. The Monte Carlo optimization was capable of being an efficient in silico tool for developing a model of good statistical quality. The predictive potential of the applied approach was tested and the robustness of the model was proven using different methods. The results obtained from molecular docking studies were in excellent correlation with the results from QSAR studies. This study can be useful in the search for novel anti-tuberculosis therapeutics based on InhA inhibition. Communicated by Ramaswamy H. Sarma

Acute–Phase Inflammatory Response in Patients with Pulmonary Tuberculosis

Summary The main issue in patients with pulmonary tuberculosis (PTB) represents the impossibility of the host immune response to express bactericidal function and the sterilization of lesions depends exclusively on the specific antimicrobial chemotherapy. In order to investigate the value of acute-phase inflammatory response markers in patients with newly confirmed extensive PTB, there was designed a clinical study with 80 patients, of whom 40 had active disease (experimental group), while other 40 had inactive sequellar disease without comorbidity (control group). The examined groups were homogenous with respect to the patient’s general demographic characteristics. In the experimental group, 20.0% of the patients had an initial bacterial infection of the lower respiratory tract, while their average value of acute-phase systemic inflammatory markers was initially, before the antituberculosis treatment, significantly elevated compared to the control group. At the end of the treatment, values of erythrocyte sedimentation rate in the first hour (SE) and serum C-reactive protein (CRP) significantly decreased (SE-p <0.001, CRP-p<0.001), together with the value of the leukocyte count (Le) and serum fibrinogen (Le-p<0.001, fibrinogen-p<0.001). Multivariate linear regression analysis proved a significant correlation between baseline serum fibrinogen level with positive history of contact with active TB patient and initial radiological extent of PTB lung lesions. The values of the acute-phase inflammatory response markers in active PTB have its clinical significance in the assessment of unfavourable course of disease in extensive disseminated form of PTB as well as in the occurrence of complications associated with low respiratory tract bacterial superinfection. Sažetak Osnovni problem kod obolelih od plućne tuberkuloze (PTB) predstavlja nemogućnost imunog odgovora domaćina da ispolji baktericidnu funkciju, te je sterilizacija lezija zavisna isključivo od sprovođenja specifične antimikrobne hemoterapije. U cilju ispitivanja vrednosti rutinskih markera akutno-faznog sistemskog inflamatornog odgovora kod obolelih od novootkrivene ekstenzivne PTB dizajnirana je klinička studija na planiranih 80 bolesnika, od kojih je 40 bilo sa novootkrivenom dijagnostikovanom PTB (eksperimentalna grupa), a 40 sa posttuberkuloznim sekvelama bez komorbiditeta (kontrolna grupa). Ispitivane grupe su bile homogene u odnosu na opšte demografske karakteristike bolesnika. U eksperimentalnoj grupi obolelih 20.0% ispitanika je imalo inicijalnu bakterijsku infekciju donjih disajnih puteva, a prosečne vrednosti ispitivanih markera sistemske inflamacije su inicijalno na početku lečenja PTB bile signifikantno povišene u odnosu na kontrolnu grupu, da bi na kraju lečenja vrednosti brzine sedimentacije eritrocita u prvom satu (SE) i serumskog C-reaktivnog proteina (CRP) statistički značajno opale do subkliničkih vrednosti (SE-p<0,001; CRP-p<0,001;), a vrednosti broja leukocita (Le) i serumskog fibrinogena signifikantno snizile i normalizovale (Le-p<0,001; fibrinogen-p<0,001;). Multivarijantnom linearnom regresionom analizom dokazana je statistički značajna povezanost između vrednosti serumskog fibrinogena na početku lečenja PTB i pozitivne anamneze kontakta sa obolelim od TB i stepena radiološke proširenosti specifičnih plućnih promena na početku lečenja PTB. Vrednosti markera akutno-faznog sistemskog inflamatornog odgovora imaju klinički značaj u proceni eventuanog nepovoljnog toka bolesti kod ekstenzivnih diseminovanih oblika PTB, kao i pojave komplikacija u smislu pridružene bakterijske superinfekcije.