THE COMBINATION OF CHRONIC RESPIRATORY DISEASES WITH OBSTRUCTIVE SLEEP APNOEA SYNDROME IN CLEAN-UP WORKERS OF CHORNOBYL NPP ACCIDENT. / ПОЄДНАННЯ ХРОНІЧНИХ ЗАХВОРЮВАНЬ ОРГАНІВ ДИХАННЯ ІЗ СИНДРОМОМ ОБСТРУКТИВНОГО АПНОЕ/ГІПОПНОЕ СНУ В ОСІБ, ЯКІ ПОСТРАЖДАЛИ ВНАСЛІДОК АВАРІЇ НА ЧОРНОБИЛЬСЬКІЙ АЕС.

The objective of the study was to establish the relationship between functional status of bronchopulmonary system and obstructive sleep apnea in clean-up workers of Chornobyl NPP accident in a remote post-accident period. MATERIALS AND METHODS: We included 58 COPD male patients clean-up workers of Chornobyl NPP accident: 21 with obstructive sleep apnea syndrome (OSA), 37 - without. A complex of functional tests and OSA screening was provided. RESULTS: In clean-up workers of Chornobyl NPP accident with COPD and obstructive sleep apnea in a remote post-accident period apnea-hypopnea index (AHI) negatively correlated with FVC, % of predicted (r = -0.36, p < 0.05), the intrathoracic gas volume (ITGV), % of predicted (r = -0.40, p < 0.05); AHI positively correlated with diffusion lung capacity (DLCO), % of predicted values (r = 0.57, p < 0.05), with the intrathoracic gas volume (ITGV), % of predicted (r = 0.53, p < 0.05), body mass index (r = 0.49, p < 0.05) and age (r = 0.62, p < 0.05). CONCLUSIONS: Obstructive sleep apnea was diagnosed in 36.3 % of patients with COPD clean up workers of Chornobyl NPP accident. Screening for OSA in patients with COPD, clean-up workers of Chornobyl NPP accident is a very important clinical task for prognosis and treatment.

MEDICAL EXPERTISE FOR ESTABLISH CAUSATION OF DISEASE, LEADING TO LOSS OF HEALTH, DISABILITY AND DEATH WITH THE ACTION OF IONIZING RADIATION AND OTHER HARMFUL FACTORS OF THE CHORNOBYL ACCIDENT IN THE REMOTE POST-ACCIDENTAL PERIOD (2013-2022). / MEDYChNA EKSPERTYZA VSTANOVLENNIa PRYChYNNOGO ZV'IaZKU ZAKhVORIuVAN', ShchO PRYZVODIaT' DO VTRATY ZDOROV'Ia, INVALIDNOSTI TA SMERTI VNASLIDOK DIÏ IONIZUIuChOGO VYPROMINIuVANNIa TA INShYKh ShKIDLYVYKh FAKTORIV ChORNOBYL'S'KOÏ KATASTROFY U VIDDALENOMU PISLIaAVARIINYINOMU PERIODI (2013­2022 rr.).

Loss of health and workability, as well as deaths due to harmful influence of the Chornobyl Catastrophe (including radiation exposure) during performance of professional, military or official duties and / or living on radiation-contaminated areas, additional exposure not through their own fault but due to a radiation accident, caused the development of a special form of medical expertise as part of the of medical social protection system for these suffered contingents. OBJECTIVE: To study and characterize the structure of the affected categories (clean-up workers and victims) of the Chernobyl Catastrophe based on the materials of expert cases of the Central Interdepartmental Expert Commission (CMEC) in the remote post-accidental period (2013-2022). MATERIAL AND METHODS: The work was performed in the design of a retrospective study that based on studying of 50,974 expert cases, which were considered by CIEC during 2013-2022 to establish a causal relationship between the disease and influence of radiation exposure and other harmful factors and conditions during ChNPP accident using a systematic analytical approach to assessing the medical and nonmedical parameters presented in medical expert documentation. RESULTS: The total number of affected adult citizens as on 01.01.2022, compared to 2008, decreased by 477,953 persons, or by 26.05 % (from 1,834,536 to 1,354,746 persons). The number of clean-up workers of the accident decreased from 276,327 (2013) to 171,725 (2022), or by 104,602 people (37.85 %), that means - during the last 10 years, almost every third clean-up worker who participated in the liquidation of the consequences of the accident at the Chernobyl NPP died. The number of adult victims decreased from 1,558,209 in 2008 to 1,183,021 in 2022, or by 24.08 % (375,188 persons). The average annual reduction in the absolute number of clean-up workers of ChNPP accident during 2013-2022 is about 7,770 people per year (9,424 during 2021), adult victims - 27,045 people per year (28,922 during 2021). In the structure of medical expert cases during 2013-2022 the leading place as the reason of disease, disability and death is occupied by oncological diseases - 52.72 %, cerebrovascular diseases and their complications make up 17.08 %, diseases of the cardiovascular system - 19.6 %. CONCLUSION: In the remote post-accidental period (2013-2022) has increased the need of expertise of the causal relationship of disability and the causes of death with the influence of the Chornobyl NPP accident consequences for medical and social support. During 2013-2022 period quick reducing for all categories of affected due to the Chornobyl NPP accident taken place. In the structure of medical expert cases during 2013-2022 the leading place as the reason of disease, disability and death is occupied by oncological diseases.

THE BRONCHOPULMONARY SYSTEM DAMAGE UNDER THE INFLUENCE OF IONIZING RADIATION EXPOSURE AND RADIONUCLIDES INHALATION IN THE CONDITIONS OF THE CHORNOBYL CATASTROPHE (SUMMARIZING OF 35 YEARS RESEARCH EXPERIENCE). / URAZhENNIa BRONKhOLEGENEVOÏ SYSTEMY VNASLIDOK VPLYVU IONIZUIuChOGO OPROMINENNIa TA INGALIaTsIINOGO NADKhODZhENNIa RADIONUKLIDIV V UMOVAKh ChORNOBYL'S'KOÏ KATASTROFY (UZAGAL'NENNIa DOSVIDU 35 ROKIV DOSLIDZhEN').

The review is devoted to the summarizing of 35 years of research of ionizing radiation exposure and radionuclidesinhalation influence on the bronchopulmonary system of clean-up workers of the Chornobyl NPP accident. Radiationand hygienic preconditions for the formation of chronic respiratory pathology are considered, taking into accountthe dosimetric data of irradiation of the bronchopulmonary system.The main clinical symptoms, features of disorders of pulmonary ventilation capacity and endoscopic forms of lesionsof the bronchopulmonary system of participants in the liquidation of the accident were determined.On the basis of pathomorphological, microbiological and immunological researches the pathomorphosis of chronicnonspecific lung diseases in the conditions of the Chernobyl catastrophe is proved.It is proved that under combined influence of external irradiation and inhalation of a fragmentary mixture ofradionuclides in the condition of the Chernobyl catastrophe, the bronchopulmonary system has become one of themain «targets¼-tissues, of realization of stochastic and nonstochastic effects.

CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE. / ZMINY GENNOÏ EKSPRESIÏ, ASOTsIIOVANI Z NEPUKhLYNNYMY EFEKTAMY VIDDALENOGO PERIODU PISLIa OPROMINENNIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES.

OBJECTIVE: to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. MATERIALS AND METHODS: We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years(M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the controlgroup: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1,IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined inperipheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The«gene-disease¼ association was determined on statistical models stratified separately for each disease and gene.Logistic regression was used to calculate the odds ratio. RESULTS: Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression werefound in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53,VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases anincrease of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activationof the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes ofangiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-upworkers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantlyupregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. CONCLUSIONS: Changes in the expression of genes, associated with the development of somatic pathology in theremote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2,IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A,SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF.

LUNG FUNCTION AND TELOMERE RELATIVE LENGTH IN CLEAN-UP WORKERS OF CHORNOBYL NPP ACCIDENT IN A REMOTE POST-ACCIDENT PERIOD. / FUNKTsIONAL'NYY̆ STAN BRONKhOLEGENEVOÏ SYSTEMY TA VIDNOSNA DOVZhYNA TELOMER V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES U VIDDALENOMU PISLIaAVARIY̆NOMU PERIODI.

OBJECTIVE: The objective was to study the relationship between functional status of bronchopulmonary system and telomere length in clean-up workers of Chornobyl NPP accident in a remote post-accident period. MATERIALS AND METHODS: A study was performed in 113 clean-up workers of Chornobyl NPP accident. Individual do- cumented doses of irradiation in clean-up workers ranged from 1,0 to 880 mSv (330.4 ± 317.7 (M ± SD)). The aver- age age of the Chornobyl NPP participants was (62.21 ± 6.99) years. A complex of functional pulmonary tests (spirometry, body plethysmography, examination of lung diffusion capacity) was performed. Relative telomere length (RTL) was analysed by flow-FISH. RESULTS: There was a tendency to decrease the relative telomere length in clean-up workers with COPD I-II stage and COPD III-IV, compared with patients with the absence of bronchopulmonary diseases (RTL 15,2 ± 2,7). Significantly shorter telomeres were observed in patients with COPD who were exposed to radiation at a dose of more than 500 mSv (13.6 ± 2.5) compared with COPD patients who were exposed at a dose <10 mSv (RTL 15.3 ± 2.3). When analyzing the correlation relationships of the studied indicators, no significant associations were found with the relative telomere length. At this stage of the study no association of relative telomere length with age, body mass index, and functional criteria (FEV1 (l), intrathoracic pressure (ITGV), total lung capacity (TLC), diffusion lung capac- ity (DLCO)) was detected. CONCLUSIONS: The analyzed telomere length relationship from liquidators of the Chernobyl found no direct associa- tion with indicators of lung function tests, however, showed a trend towards reducing the relative telomere length in clean-up workers who suffer from COPD and exposed to doses from 100 to 500 mSv and above 500 mSv.

СHRONIC OBSTRUCTIVE PULMONARY DISEASE IN THE CLEAN-UP WORKERS OF CHORNOBYL NPP ACCIDENT IN A REMOTE POST6ACCIDENT PERIOD (CLINICAL STUDY). / KhRONIChNE OBSTRUKTYVNE ZAKhVORIuVANNIa LEGEN' V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES U VIDDALENOMU PISLIaAVARIINOMU PERIODI (KLINIChNE DOSLIDZhENNIa).

OBJECTIVE: to study the clinical differences in the course of chronic obstructive pulmonary disease in the clean-upworkers (CW) of Chornobyl nuclear power plant (ChNPP) in the remote post-accident period (30 years after the effectof radiation exposure). MATERIAL AND METHODS: 120 CW of ChNPP were examined (47 patients with chronic obstructive pulmonary disease(COPD) and 73 patients without bronchopulmonary disease) and 50 patients in the control group (20 patients with COPDand 30 without bronchopulmonary disease). Individually documented radiation exposure doses of CW were (25.2 ± 13.7cSv, (M ± SD)). The study program included clinical examination, functional pulmonary tests, and statistical analysis. RESULTS: The negative correlation dependence (r = -0,358, p < 0,05) between the 6-minute walk rate and the age ofCOPD patients was established. Negative correlation was observed between the distance at 6-minute walk test, andforced exhalation volume for 1 sec. (FEV1) (l) (r = 0.743; p < 0.05); forced vital capacity (FVC) (l) (r = 0.692;p < 0.05), the ratio of FEV1/FEV6 (r = 0.697; p < 0.05), forced exhalation volume for 6 sec (FEV6) (l) (r = 0.727; p < 0.05),Diffusion Lung Capacity (mmol/min/kPa) (r = 0.754, p <0, 05). A positive correlation was found between the dose ofradiation exposure and the index of intra-thoracic pressure (ITGV) in the CW (r = 0.1494, p <0.05), and the values ofFEV1 and forced expiration flow (FEF75), regardless of the presence of COPD. In the subgroup of patients with COPDCW there was a significantly higher proportion of patients with cardiovascular and cerebrovascular pathology, whichcorresponded with the higher level of cholesterol compared with the control group ((5.52 ± 1.34) mmol/l and(4.46 ± 1.74) mmol/l, respectively, p < 0.05). CONCLUSIONS: In the CW at the ChNPP, compared with the group of nosological control, there were significantly lowerindicators of the shortness of breath degree and the frequency of exacerbations per year, more pronounced distur-bance of exercise tolerance, higher comorbidity. Dependence of development of COPD on radiation dose and age atthis stage of research was not estimated.

Optimization of chronic obstructive pulmonary disease treatment in clean-up workers of the Chornobyl NPP accident in the remote period after irradiation. / OPTYMIZATsIIa LIKUVANNIa khvorykh na Khronichne obstruktyvne zakhvoriuvannia legen' v Uchasnykiv likvidatsii naslidkiv avarii na ChAES u VIDDALENOMU PERIODI pislia oprominennia.

BACKGROUND: According to the results of the clinical and epidemiological studies in clean-up workers of Chernobyl NPP accident in the remote period were detected the growth of morbidity of chronic obstructive pulmonary disease with substantial features of pathomorphosis, that make difficulties for treatment. The aim of the study was to determine the effectiveness of long-term administration (6 months) combination Аmbroxol (30 mg x 3 times per day) and Essenciale (600 mg x 2 times per day) added to basic treatment in patients with moderate to severe COPD - clean-up workers of the Chornobyl NPP accident. MATERIALS AND METHODS: Studied 60 COPD patients before treatment and after 1 year from the beginning, who were randomly assigned to two groups: the first group of patients ( 32 persons ) additionally was appointed long reception (6 months) combination ambroxol (30 mg three times a day ) and Essenciale (600 mg twice daily ), in the second group (28 people) patients received only basic therapy. The doses of radiation exposure were 25 - 500 mSv. Were studied clinical, functional characteristics, the number of exacerbations. RESULTS AND CONCLUSIONS: Low response to the basic COPD therapy were shown by clean-up workers of the Chornobyl NPP accident, which is defined by the absence of significant changes in lung function tests. Additional appointments to the basic treatment of COPD ambroxol combination (30 mg 3 g / d) of Essenciale (600 mg 3 g / d) within 6 months of the liquidators of the Chernobyl possible to reduce the frequency of exacerbations in 46.9% patients without significant improvement in lung function tests.

Analysis of risk factors for chronic obstructive pulmonary disease in clean-up workers of the Chornobyl accident. / Analiz faktoriv ryzyku hronichnogo obstruktyvnogo zahvorjuvannja legen'' v uchasnykiv likvidacii' naslidkiv avarii' na ChAES.

Objective. To analyze the effects of ionizing exposure, age and smoking on the development of chronic non-specific lung disease in a cohort of liquidators of the Chornobyl consequences included in the Clinical and Epidemiological Registry SI "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine". Materials and methods. The analysis included data on 7156 of the Chornobyl liquidators, of which 6 257 (87.4 %) men and 899 (12.6 %) women who were examined between 1993 and 2010 by pulmonologist. Results. Chronic bronchopulmonary diseases were detected in 50.0 % of the surveyed persons. The overall exposure dose was significantly higher among liquidators, which developed bronchopulmonary diseases (24.29 ± 0.82 sSv) compared with those without bronchopulmonary disease (14.58 ± 0.62 sSv), p = 0.001. In smokers the incidence of chronic obstructive pulmonary disease was twice higher than in those who did not smoke (10.2 and 5.16 %, respectively, p = 0.0001). Conclusion. The negative effect of ionizing radiation amplified by other risk factors for chronic bronchopulmonary disease: association between exposure doses and somatic pathology manifested in the surveyed people over the age of 45 years; at the same exposure dose risk of bronchopulmonary diseases was higher for smokers.

Late effects of ionizing radiation on functional status of bronchopulmonary system in COPD patients among the clean-up workers of the Chornobyl NPP accident. / Viddaleni efekty vplyvu ionizujuchogo vyprominjuvannja na funkcional''nyj stan bronholegenevoi' systemy u hvoryh na hozl uchasnykiv likvidacii' naslidkiv avarii' na ChAES.

The objective of the study was to determine the effects of ionizing radiation on the functional condition of the bronchopulmonary system in clean-up workers of Chornobyl NPP patients with COPD in a remote post-emergency period. Materials and methods. The study of functional characteristics was carried out in 272 patients - 197 clean-up workers of Chornobyl NPP accident (ChNPPA) with radiation exposure from 25 to 988 mSv; 75 - group of nosological control and 20 healthy persons. Results and conclusions. For the clean-up workers of Chornobyl NPP with exposure doses over 500 mSv demonstrated correlation between respiratory function parameters and dose which is confirmed for these patients, compared with irradiated in doses less than 500 mSv and nosology control, a significant decreasing of VC (76,3 ± 8,5%, 82,4 ± 8,5% and 82,7 ± 8,1% accordingly, p <0,05), FVC (78,2 ± 8,3%, 84,3 ± 7,9% і 86,1 ± 9,7%, p <0,05), FEF 50 (26,1 ± 11,5%, 32,6 ± 10,6% і 32,1 ± 12,7%, p <0, 05) і FEF 75 (23,8 ± 8,1%, 27,8 ± 9,3% і 27,6 ± 9,2%, p <0,05). These changers combined with decrease in lung diffusion capacity in cases more than 500 mSv, and indicate severe respiratory disorders in patients with COPD among clean-up workers of ChNPPA.