УДК 616.24:612.1]-06

Leptin, a hormone produced by white adipose tissue and recognised as an inflammatory biomarker, has an undefined role in the progression of chronic obstructive pulmonary disease (COPD). Objective — to evaluate the leptin level and its correlations with the levels of clinical, functional and anamnestic indicators in COPD patients.
Materials and methods. This study employed a case-control design involving 42 patients experiencing acute exacerbation of COPD and 20 control subjects. The patients were examined according to the standard protocol. Additionally, the examination included ultrasonic scanning of the abdominal cavity, evaluation of the serum leptin level, scoring of the anxiety and depression and quality of life.
Results and discussion. It was revealed that hyperleptinemia in the patients with acute exacerbation of COPD occurred significantly more frequently than in the healthy persons ((73.8 ± 6.8) vs (40.0 ± 11.0) %; р < 0.05). Besides, the COPD patients manifested increased leptin levels much more frequently than normal levels ((73.8 ± 6.8) vs (26.2 ± 6.8) %; р < 0.01). Hyperleptinemia was found to co-occur with severe COPD 
cases belonging to E clinical group ((51.6 ± 9.0) vs (18.2 ± 11.6) % in group with normal leptin level; р < 0.05). Kendall correlation analysis established that elevated circulating leptin levels were associated with an increased body mass index ( = 0.3; р = 0.02), female gender ( = 0.3; р = 0.01), non-smoking history ( = – 0.2; р = 0.03), stronger manifestation of such symptoms as shortness of breath ( = 0.3; р=0.01), disturbed home ( = 0.3; р = 0.002) and out-of-home activities ( = 0.3; р = 0.02) and lack of energy ( = 0.3; р = 0.01). It also correlated with increased severity of pulmonary insufficiency ( = 0.3; р = 0.003) and decreased forced vital capacity (= – 0.2; р = 0.04), elevated systolic blood pressure ( = 0.2; р = 0.02), elevated cholesterol ( = 0.3; р = 0.01) and -lipoproteins levels ( = 0.2; р = 0.04), pronounced depression ( = 0.3; р = 0.002) and lowered quality of life ( = 0.3; р = 0.01).
Сonclusions. COPD patients with elevated leptin levels manifest not only with an increased body weight, but also with arterial hypertension, disturbed lipid metabolism, more pronounced pulmonary insufficiency, depressive disorders and lowered life quality with more severe subjective respiratory symptoms.
Keywords. Chronic obstructive pulmonary disease, leptin, hyperleptinemia

УДК 616.002.5-021.3-053.8-035.7

Objective — to study the frequency and causes of diagnostic errors in primary pulmonary tuberculosis (PrPTB) in adults.
Materials and methods. The frequency and causes of diagnostic errors in verifying PrPTB in adults were studied by analyzing thpathomorphosis aspect of a specific process. Sectional material from 200 adult deaths due to primary forms of tuberculosis (PrFTB) over a period of 45 years (1974—2020) was analyzed. The study period was divided into three periods: the first period spanned from 1974 to 1988, during which three 
antimycobacterial drugs (isoniazid, streptomycin, and PASC) were used; the second period ranged from 1989 to 2005, during which rifampicin, ethambutol, and pyrazinamide were added to the treatment regimen; and the third period covered from 2005 to 2020, during which aminoglycosides, fluoroquinolones, linezolid, and other antimycobacterial drugs were widely utilized.
Results and discussion. Studies conducted on clinical and pathological material from 200 deaths related to primary forms of tuberculosis (PrFTB) over the last 45 years (1974—2020) based on data from prosectures in Lviv indicate a significant decrease in the number of deaths from primary pulmonary tuberculosis (PrPTB) among the adult population. This decline is attributed to the widespread adoption of modern antimycobacterial therapy for patients with pulmonary tuberculosis (PTB). The predominant clinico-pathological form of PrPTB is tuberculosis of the intrathoracic lymph nodes (TBILN), which manifests with various progression variants. Complications of a specific nature (such as miliary TB, TB meningitis, and TB sepsis) prevail among the direct causes of death. However, diagnosing PrPTB in adults poses significant challenges in modern conditions, with an increasing frequency of underdiagnosis over the years. Diagnostic errors most commonly occur in general diagnostic hospitals during the verification of TBILN and its complications in patients over 30 years old.
Conclusions. The frequency of underdiagnosing PrPTB has increased due to its atypical course, likely resulting from the pathomorphosis of a specific process. The discrepancy between clinical and pathoanatomical diagnoses, attributable to the unique clinical course of PrPTB, was observed in 7.3 % of cases in the first period, 27.2 % in the second, and 40.0 % in the third. Several factors contribute to the underdiagnosis of PrPTB, including short-term hospital stays, the atypical course of PrPTB due to the pathomorphosis of a specific process, inadequate patient examination, the lack of urgency for phthisiological evaluation in general medical institutions and incorrect interpretation of clinical, radiological and laboratory data.
Keywords Primary tuberculosis in adults, diagnosis, errors

УДК: 614.71:661.162.2:615.099

Мета. Встановлення параметрів токсичності та обгрунтування гранично допустимої концентрації гербіциду клопіраліду в повітрі робочої зони.
Об’єкт і методи дослідження. Клопіралід (3,6-дихлорпіридин-2-карбонова кислота) виробництва фірми SUPERUS Co. Ltd (Китай). Методи досліджень – токсиколого-гігієнічні, біохімічні, імунологічні, фізико-хімічні, статистичні.
Результати дослідження та їх обговорення. Представлені результати токсиколого-гігієнічних досліджень гербіциду клопіраліду на лабораторних тваринах (білі миші, білі щурі, мурчаки, кролі). Встановлено, що клопіралід за параметрами гострої токсичності при одноразовому внутрішньошлунковому введенні та однократному нанесенні на шкіру відноситься до малонебезпечних речовин (4 клас небезпечності), при однократному інгаляційному впливі - до помірно небезпечних речовин (3 клас небезпечності), не володіє шкірно-резорбтивною дією, проявляє середньо виражений подразнювальний ефект при багаторазовому попаданні на шкіру та сильно виражений подразнювальний ефект при попаданні на слизові оболонки, викликає сенсибілізацію організму. При субхронічному пероральному впливі та багаторазовому нанесенні на шкіру проявляє слабкі кумулятивні властивості. Гонадотоксичний, ембріотоксичний та тератогенний ефекти обумовлені загальнотоксичною дією клопіраліду. Генотоксичних та канцерогенних властивостей не виявлено. На підставі встановлених параметрів токсичності розраховано коефіцієнт запасу, запропоновано гранично допустиму концентрацію клопіраліду у повітрі робочої зони та розроблено методику вимірювання масової концентрації препарату.
Висновки. Гранично допустима концентрація клопіраліду у повітрі робочої зони рекомендується на рівні 1,0 мг/м3, аерозоль, 2 клас небезпечності, позначка + - потребує спеціального захисту очей. Розроблено газохроматографічну методику вимірювання масової концентрації клопіраліду у повітрі.

Goal. Establishment of toxicity parameters and substantiation of the maximum permissible  concentration of the herbicide clopyralid in the air of the working area.

Object and research methods. Clopyralid (3,6-dichloropyridine-2-carboxylic acid)  manufactured by SUPERUS Co. Ltd (China). The research methods are toxicological-hygienic,  biochemical, immunological, physico-chemical, statistical.

Research results and their discussion. The results of toxicological and hygienic studies of the herbicide clopyralid on laboratory animals (white mice, white rats, ants, rabbits) are presented.  It was established that clopyralid according to the parameters of acute toxicity with a single  intragastric injection and a single application to the skin belongs to low-hazard substances (hazard class 4), with a single inhalation effect - to moderately hazardous substances (hazard class 3), does not have a skin resorptive effect, exhibits moderately pronounced irritant effect upon repeated contact with the skin and strongly pronounced irritant effect upon contact with mucous membranes, causes sensitization of the body. With subchronic oral exposure and application to the skin, it exhibits weak cumulative properties. Gonadotoxic, embryotoxic and teratogenic effects are caused by the general toxic effect of clopyralid. Genotoxic and carcinogenic properties were not detected. Based on the established parameters of toxicity, the stock factor was calculated, the maximum permissible concentration of clopyralid in the air of the working area was proposed and the method of measuring the mass concentration of the herbicide was developed.

Conclusions. The maximum permissible concentration of clopyralid in the air of the  working area is recommended at the level of 1.0 mg/m3, aerosol, 2nd hazard class, + - mark  requires special eye protection. A gas chromatographic technique for measuring the mass concentration of clopyralid in air has been developed

UDC: 616.24-002.5:615.015.8]-085.281-078.73-092-036

Immunological methods are important for diagnosing tuberculosis, evaluating the process activity, and forecasting the course of the disease and recovery. 
Materials and methods. 47 patients with first diagnosed destructive sputum smear-positive pulmonary tuberculosis underwent a complex immunoassay. The patients were divided into two groups based on the sensitivity/resistance of mycobacterium tuberculosis to antimycobacterial agents. The first group consisted of 22 patients with first-diagnosed chemosensitive tuberculosis with preserved sensitivity to antimycobacterial agents. The second group consisted of 25 patients with multi-drug resistant tuberculosis pulmonary tuberculosis (MDR-TBP). 
The research was conducted during the 2018-2021 years. Results Specific cell response disorders in patients with pulmonary tuberculosis are associated with the multistructural T-cell protection misbalance caused by the quantitative changes of its components, the increase/decrease in the quantity of certain lymphocyte pools specifying the immune response vector. In cases of tuberculosis, phagocytosis plays an important role. Phagocytosis might release cells from the tuberculosis pathogen. To achieve this, the activation of cells should reach a certain level. However, the initial protective nature of cell activation might become aggressive. The T-cell immunity disorders were more evident in patients with MDR-TBP versus donors and patients with chemosensitive tuberculosis. The apparent decrease in СD3+СD56+, СD3+СD4+ pools and the increase in СD3+СD8+ were revealed in cases of MDR-TBP tuberculosis versus chemosensitive tuberculosis. The difference in СD3+СD4+, СD3+СD8+, СD3+СD4+/СD3+СD8+, CD3+СD8+HLA-DR+, СD16/56+8+ between the study and observational groups was statistically confirmed. The evident specific cell immunity disorders in patients with MDR-TBP aggravate the clinical course of the disease, causing destructive changes and acute and extensive processes. Conclusions Changes in different components of the immune system might occur during pulmonary tuberculosis (in T- and B-cells, phagocytic cells), specific and enzymatic processes are activated, and autoimmunization is evident. The intensity of the changes varies at different stages of the disease. Most immune disorders caused by the specific inflammation process require immune correction
Keywords: immune responsiveness, phagocytosis, T- and B-cell immunity, multi-drug resistant and chemosensitive tuberculosis 

UDC 616.24-002.5:615.015.8]-085.281-036.8-053.2/.6

Introduction. Against the backdrop of multiple and widespread drug resistance of Mycobacterium tuberculosis (MDR-TB), there has been 
a significant decline in the effectiveness of treatment of tuberculosis (TB) patients in Ukraine and globally. Therefore, in recent years, new 
antimycobacterial drugs, such as bedaquiline (Bdq), delamanid (Dlm) and pretomanid, have been introduced to improve treatment efficacy 
 in adults, children and adolescents.
Purpose. To study the effectiveness of complex treatment with bedaquiline (Bdq) and delamanid (Dlm) in children under 18 years old with 
multiple and extensively drug-resistant pulmonary TB (MDR/XDR-TB).
Materials and methods. To study the clinical efficacy of chemotherapy with Bdq and Dlm, a retrospective cohort analysis of medical 
records was conducted. The main group consisted of 40 children with MDR/XDR-TB who received comprehensive antimycobacterial therapy 
with Bdq and Dlm; and the control group consisted of 27 patients who received treatment without Bdq and Dlm.
Results. It was found that during the first three months of treatment, there was a decrease in bacilli in all patients treated with Bdq and Dlm and in the group of patients without these new drugs (control), but in the control group, the decrease was significantly slower, p<0.05. According to the immune system parameters, after the intensive phase was completed, the activity of a specific process was 1.7 times more frequent in patients of the control group than in the main group. After completion of the course of treatment, all patients in the main group showed resorption of infiltration, compaction of foci, and formation of fibrosis in the lungs according to the results of X-ray tomographic examination. However, in 14.8% of patients in the control group, treatment failure was noted with the resumption of bacterial release and destruction in the lung tissue, and in the main group, all patients had healing of the decay cavities. In the majority (77.5%) of patients in the main group, treatment resulted in the formation of small residual changes, but large residual changes were 2.3 times more common in the control group in the form of multiple dense foci, fibrosis and residual decay cavities.
Conclusions. Studies have shown the high efficacy of complex treatment with Bdq and Dlm in children and adolescents. In particular, in MDR/XDR-TB patients treated with Bdq and Dlm, treatment results were 2 times more likely to be considered «cured» than in the control group, and 1.5 times less likely to be considered «complete». The treatment success rate in the main group was 100.0%, and in the control group — 85.2%. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: children, tuberculosis, adolescents, multidrug resistance, extensive drug resistance, treatment, bedaquiline, delamanid