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Data analysis of numerous studies was carried out and trends and directions in the management of patients 
with сhronic obstructive pulmonary disease (COPD) were analysed. Studying the characteristics of factors 
contributing to disease development без коми allows us to understand that the smoking epidemic, the aging of 
the world population and the lack of disease-modifying therapy will lead to a further increase in mortality from 
COPD. Each COPD exacerbation increases both the risk and frequency of subsequent exacerbations, and the 
development of local or systemic changes and complications has also been established. Not only severe but also 
moderate COPD exacerbations (those that do not require hospitalization and could be treated on an outpatient 
basis) also increased the risk of subsequent exacerbations and death. The degree of increase in risk was propor-
tional to the number of exacerbations per year. Thus, two moderate exacerbations per year increased the risk of 
death by 80 % (hazard ratio — 1.80 (95 % confidence interval (CI): 1.19—2.70)), while increased frequency of 
exacerbations to 5 increased the hazard ratio to 2.33 (95 % CI: 1.45—3.76).
The effectiveness of the treatment of patients with COPD and the dependence of the latter on various factors 
were evaluated. Based on the received data, the specialists have concluded that the presence of one severe or 
two or more moderate COPD exacerbations during one year indicates a high risk of exacerbations in the future 
and is associated with an increased risk of premature death. Therefore, a high-risk group patient requires special 
attention when choosing the tactics of his management. This is reflected both in international and national 
consensus documents. A single-inhaler triple therapy (specifically a fixed combination of budesonide/glycopyr-
ronium/formoterol), administered within the first 30 days after an exacerbation, is currently the only pharma-
cotherapeutic option that has been proven to reduce mortality in COPD patients.
Keywords 
Сhronic obstructive pulmonary disease, modifying factors of exacerbations, effective three-component therapy, 
mortality prevention.

ABSTRACT
The aim: To evaluate the dynamics of the interferon and collagen-IV systems in bronchoalveolar lavage in the treatment of chronic obstructive pulmonary disease using the tiotropium bromide medication.
Materials and methods: The study involved 60COPD patients with bronchial obstruction of the II degree before and on days 30 and 60 of therapy using conventional treatment regimens and inhalations of tiotropium bromide a the dose of 18 mcg once a day.The collagen-IV levels in bronchoalveolar fluid were determined by means of enzyme-linked immunoassay using “StatFax 303 Plus” analyzer and “Biotrin Collagen IV EIA” reagents. The level of IFN-γ was identified with the help of enzyme-linked immunoassay using “StatFax 303 Plus” analyzer and “ProKon” reagents (LLC “Protein Contour”, Russia) in bronchoalveolar fluid obtained during fiber-optic bronchoscopy.
Results: When examining GroupI patients on the 30th day we found out that the content of collagen-IV in the bronchoalveolar fluid had decreased by only 10.29% (p <0.05).
Detection of collagen-IV indices in Group II patients on the 30th day of tiotropium bromide use showed the 29.43% (p <0.05) decrease in its content as compared to the initial indices. In Group III patients, the concentration of collagen-IV had a maximum tendency to normalize and made up (24.72 ± 1.15) ng/ml, and decreasedby 2.44 times (p <0.05) as compared to the initial indices. Our examination of 12 patients from the comparison group I on the 60th day of treatment revealed even a slight increase in the content of collagen-IV in the bronchoalveolar fluid, as compared with the data obtained on the 30th day. Theidentified IFN-γ deficiency is indicative for the COPD of the II degree of bronchial obstruction, and its indices were 2.29 times lower than those observed in people from the control group. On day 30, we found out that the content of IFN-γ in Group I patients increased by only 10.29% (p>0.05). Detection of IFN-γ in Group II patients showed 42.27% (p<0,05) increase in its content as compared to the initial indices. The most favorable dynamics of IFN-γ levels in bronchoalveolar contents wasobservedin Group III patients, and at the time of observation itmadeup (1.16 ± 0.08) pg/ml, having 2 times (p<0.05) increasedas comparedtotheinitial indices. However, in contrast to those taking tiotropium bromide, we examined 12 patients from Group I on the 60th day of treatment and found no significant positive dynamics of IFN-γ content in bronchoalveolar fluid as compared to the indices obtained on day 30.
Conclusions: The obtained findings indicate the effect of tiotropium bromide on the reduction of interferon-γ and reduce of collagen-IV levels, which depend on the duration of its use.