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  • Author: Yavor Y. Ivanov x
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Introduction: Pharmacoeconomics (PE) treats the problems of pharmacotherapy policy, drug marketing and reimbursement and clinical trials. It guides policy makers for effective health resources utilization and determines the profitability of the new drugs on the basis of their price, efficacy and benefits for society.

Types of health costs and pharmacoeconomic analyses: In the current review the main types of health costs are discussed. The main PE analyses with their advantages and disadvantages are presented.

Pharmacoeconomic of bronchial asthma: The main aspects of PE of bronchial asthma are available in the current review. The costs of health services (direct and indirect), the educational programs and asthma medications in different countries are discussed. Recently published data showed correlation between asthma cost and disease severity, control, social status and therapy adherence.

Conclusion: PE analyses provide the benefit of making cost consistent decisions in the field of asthma care. This review adds more data on the cost of current asthma treatment worldwide and in Bulgaria.


Deciding on a treatment approach for early stage lung cancer (0-1) is sometimes difficult because of uncertainties regarding the depth of tumour invasion and its margins. Even with advanced technology, such as endobronchial ultrasound and autofluorescence bronchoscopy, it is often difficult to be precise. In this currently discussed case, treatment of a 61-year-old female patient with early stage IA lung cancer could not proceed for such reasons. Fortunately, timely surgical intervention allowed preservation of lung function and the patient is now under close surveillance.


As part of a retrospective study on bronchoscopies performed at the Clinic of Pneumonology and Phthisiatry of the University Hospital – Pleven by autofluorescence bronchoscopy we found 3 cases diagnosed with carcinoma in situ. They were treated in different ways – endobronchial electrocoagulation, extraction by forceps biopsy and open surgery, but the result was the same – clinical healing. The paper presents the three clinical cases and the analysis of the treatment.


Background: Autofluorescence bronchoscopy (AFB) allows a more sensitive approach to the diagnosis of premalignant and malignant endobronchial lesions than white light bronchoscopy (WLB) can do.

Aim: To assess the autofluorescence bronchoscopy and white light bronchoscopy in diagnosing malignant endobronchial lesions.

Materials and methods: The design of the study is a retrospective case-control study. Thirty-two parameters were entered into an Excel file and analysed with SPSS v. 21 for Mac book Pro. Endoscopy findings were graded in 4 options and morphological results - in 9 options according to WHO classification. The results are presented using McNemar’s test and sensitivity, specificity and positive and negative predictive values as well.

Results: Three hundred and three patients were included in the study. Lung cancer was found in 38.3% of the patients using histology and in 35.6% - using cytology. McNemar’s test for AFB finding for suspected and malignant lesions OR was 8.333 (95% CI 3.571-23.784) while for WLB OR was 0.128 (95% CI 0.045-0.299). For cytological results OR was 3.800 (95% CI 2.123-7.227) and 3.471 (95% CI 1.996-6.351), respectively. P value was <0.0001 for all tests. Sensitivity for AFB and WLB was 94.83% but specificity was 52.83% and 55.66% if histology was used. For cytology these numbers were respectively 86.11% and 84.26% for sensitivity, and 63.69% and 62.42% for specificity.

Conclusion: AFB has an advantage over WLB in diagnosing endobronchial malignant lesions. Biopsying suspicious, not only visible malignant lesions, increased diagnostic sensitivity.


Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.


Background: At present, there is little information in Bulgaria regarding the rate and stability of frequent-exacerbation phenotype in COPD patients.

Aim: To study the rate and stability of frequent-exacerbation phenotype in COPD patients.

Materials and methods: We followed up 465 COPD patients for exacerbations over a 3-year period. Exacerbations were defined as events that resulted in treatment with antibiotics and/or corticosteroids (moderate), or that led to hospitalization (severe).

Result: Approximately 10% of the patients had two or more exacerbations per year (frequent-exacerbation phenotype), and this structure stayed stable over the study period. The exacerbation rate in the first year of follow up was 0.33 per stage I COPD patients (according to GOLD stages), 0.49 per stage II COPD patients; 0.69 - for stage III, and 1.06 for stage IV COPD patients. The frequent-exacerbation rate increased from stage I to stage IV by 4.35%, 9.17%, 10.79%, and 20.97%, respectively. A history of previous year exacerbations increased the risk of new exacerbations: with a history of one exacerbation - OR 2.1820 (95% CI: 1.4018 to 3.3965, p = 0.0005), and with a history of two exacerbations - OR 4.6460 (95% CI: 2.3286 to 9.2696; p < 0.0001). The frequent-exacerbation phenotype appeared to be unstable over the study period - up to 33% from those patients stayed in the phenotype for the next year.

Conclusions: The exacerbation frequency and the rate of frequent-exacerbation phenotype increases with COPD progression. History of exacerbations in the previous year is a significant risk factor for exacerbations of COPD. The frequent-exacerbation phenotype appeared to be unstable over the study period. The pheno-type of non-exacerbators was more likely to remain stable over time.


Background: Environmental pollution can be one of the main risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD). Aim: To study the relationship between air pollution, outdoor temperature and exacerbations of COPD. Materials and methods: COPD patients (n=1432) were followed up for one year. The levels of particulate matter up to 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and outside temperatures were collected from the Environmental Agency database. Results: A total of 309 acute COPD exacerbations (AECOPD) were recorded in the analysis. The daily mean concentrations of PM10 were found to correlate significantly with the daily mean concentrations of NO2 and SO2 (ρ 0.34 and ρ 0.49, respectively; p=0.0001). The negative correlations between the daily mean temperature and the daily mean levels of PM10, NO2 and SO2 were also significant (ρ -0.44, ρ -0.11, and ρ -0.37, respectively; p=0.0001). The daily number of AECOPD correlated with the mean levels of PM10 in the previous six days (ρ 0.14; p=0.02) and the lower outdoor temperature (ρ -0.2; p=0.001). The negative correlation between the daily number of AECOPD and the mean daily temperature was stronger in days with levels of PM10 above 50 μg/m3 (ρ -0.3 p=0.02 vs. ρ -0.18 p= 0.01). Conclusion: Lower daily mean temperatures were associated with the levels of air pollutants. The level of PM10 correlated with the levels of the other air pollutants. The daily number of AECOPD was found to correlate weakly, but signifi cantly with the mean level of PM10 in the previous six days.


The study aimed to assess the inhalation technique of patients with bronchial asthma/chronic obstructive pulmonary disease (COPD) via an objective method and to evaluate the effect of training in patients with incorrect technique. Тhe inhalation technique of 120 patients with obstructive pulmonary disease was tested. The patients were divided into two groups: using metered dose inhalers (MDI) - 34 patients (28%) and dry powered inhalers (DPI) - 86 patients (72%). The most frequent mistakes in the MDIgroup were short duration of the inhalation (55.88%) and bad synchronization between activating the canister and the inhalation (29.41%). For the DPIgroup, the inhalation was not forceful enough (48.84%) and the short duration of the inhalation (12.79%). Patients claiming to have good inhalation technique accounted for 97%of those in the MDIgroup, and 96.5%of those in the DPIgroup. There were two patients (5.88%) with correct inhalation technique in the MDIgroup at their first attempt, and 31 patients (36.05%) in the DPIgroup. We found that in the MDIgroup there wasasignificant reduction in the number of mistakes (p<0.001). In the DPIgroup, such correlation was not found but during visit 2 there were no patients with more than 1 mistake. Correcting poor inhalation technique led to reduction of the number of mistakes during inhalation.