Ovcharenko I. Prediction of the effectiveness of multidrug-resistant pulmonery tuberculosis treatment by assessing the dynamics of tissue destruction and fibrosis factors

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0420U101416

Applicant for

Specialization

  • 14.01.26 - Фтизіатрія

21-09-2020

Specialized Academic Board

Д 26.552.01

State organization "National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky National academy of medical sciences of Ukraine"

Essay

Object of research: multidrug-resistant tuberculosis. Purpose - optimization of predicting the treatment effectiveness of patients with pulmonary MDR-TB basing on assessment of indicators of lung tissue destruction, collagen disintegration and aldosterone levels. Research methods: epidemiological (treatment effectiveness), general clinical (survey, examination, history taking, blood test, urine test, blood biochemistry (including determination of oxyproline and its fractions)), microbiological (determination of MTB by bacterioscopic and bacteriological methods, drug sensitivity test to the 1st- and 2nd-line drugs), enzyme-linked immunosorbent assays (determination of aldosterone levels, MMP-9, TIPM-1), radiological, analytical and statistical. Novelty: for the first time it was found that patients with pulmonary MDR-TB compared with patients with new pulmonary tuberculosis drug-susceptible cases, have significantly lower levels of aldosterone at the beginning of treatment and after 3 months of treatment, but less pronounced dynamics of reducing its level on the background of therapy. A slower dynamics of aldosterone levels in patients with MDR-TB was found, which indicates a greater severity of destructive and fibrotic changes in them. It was determined that in patients with pulmonary MDR-TB have higher level of free hydroxyproline (FHP) after 2 months of treatment; higher levels of protein-bound hydroxyproline (PBHP) and lower levels of the tissue inhibitor metalloproteinase-1 (TIMP-1) after 3 months of treatment. It was found that patients with effective treatment had higher levels of total hydroxyproline (THP), PBHP, TIMP-1 at the beginning of treatment; lower levels of FHP after 2 months of treatment. In patients with pulmonary MDR-TB with ineffective treatment, THP, PBHP and TIMP-1 at the beginning of treatment were significantly lower, and the level of FHP was significantly higher after 2 months of treatment. During anti-TB treatment, patients with MDR-TB had significantly higher activity of fibrosis processes compared with patients with drug-susceptible TB, which increases the amount of residual changes in the lungs. Markers of risk of ineffective treatment in patients with pulmonary MDR-TB were identified: the level of MMP-9 and aldosterone in blood plasma and FHP in serum. Additional criteria for selection of patients with pulmonary MDR-/TB, who are recommended to provide anti-TB therapy and surgical treatment of tuberculosis, were developed; a mathematical model for predicting the risk of ineffective MDR-TB treatment was created. Field of application - medicine.

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