Profile of Proteases with Elastolytic Activity and Functional Respiratory Disorders in the Pathogenesis of Pulmonary Tuberculosis

Aim. To assess the profile of proteases with elastolytic activity (EA) in peripheral blood in the pathogenesis of pulmonary tuberculosis (PT) in relation to pulmonary ventilatory dysfunction and gas exchange abnormalities.

Materials and methods. A comprehensive assessment of the lung status was performed in 264 patients with verified PT without co-occurring chronic obstructive pulmonary disease. Chest computed tomography with em­physema progression quantification and pulmonary function testing (PFT) were performed, including spirometry, body plethysmography, and measurement of diffusing capacity of the lungs for carbon monoxide (DL_CO). Serum levels of matrix metalloproteinases (MMP-7, -9, -12) and their tissue inhibitor-1 (TIMP-1) were determined by ELISA using reagents from R&D Systems (Minneapolis, MN, USA), while neutrophil elastase (NE) and a₂-macroglobulin (MG) levels were measured by inhibiting synthetic substrates (ICN Biomedicals Inc., USA). Statistical analysis included the non-parametric Mann Whitney and Kruskal Wallis tests with Bonferroni correction and the Spearman’s rank correlation coefficient in Statistica 7.0. A multivariate analysis of variance (MANOVA) model was constructed in R.

Results. In the MANOVA model, a composite variable Y was derived from the biochemical markers, reflecting changes in proteases with EA in PT pathogenesis, considering the clinical form and patterns of pulmonary function impairment. In destructive disease without pulmonary function abnormalities, EA was determined predominantly by NE and MMP-12 levels. Fibrotic transformation with obstructive or mixed pulmonary dysfunction was ac­companied by a shift in the protease inhibitor balance towards increased concentrations of MMP-7 and MMP-9. Excess EA at early stages of the disease was compensated by MG, whereas at later stages, compensation was mediated by TIMP-1.

Conclusion. Alterations in the profile of proteases with elastolytic activity characterize shifts in tissue responses, reflect the development of distinct patterns of functional respiratory disorders and DL_CO reduction, and may there­fore serve as biochemical markers of evolving ventilatory dysfunction and gas exchange abnormalities in PT.

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