L.V. VASILYEVA¹, E.V. GOSTЕVA¹, E.YU. SUSLOVA¹, O.A. LEPUKHOVA², M.I. TALYKOVA¹, O.V. IVONIN¹

 ¹Voronezh State Medical University named after N.N. Burdenko, Voronezh

²Devitskaya outpatient clinic of the Semiluksky District Hospital named after A.V. Goncharov, Devitsa settlement

 Contact details:

Suslova E.Yu. — PhD (Medicine), Associate Professor of the Department of Propaedeutics of Internal Diseases

Address: 10 Studencheskaya St., 394036 Voronezh, Russian Federation, tel.: +7-951-567-02-12, e-mail: suslova_ekaterina2502@mail.ru

The established pathophysiological features of chronic obstructive pulmonary disease (COPD) are inflammation, oxidative stress, and an imbalance between proteases and their inhibitors. However, the effectiveness of MMP-9/TIMP-1, NLR, and PLR in diagnosing the severity of COPD remains uncertain.

The purpose was to evaluate the levels of systemic inflammation biomarkers and the MMP-9/TIMP-1 ratio depending on the severity of COPD.

Material and methods. An open comparative observation was conducted, which examined 72 patients (60.5 ± 5.8 years) with COPD. The inclusion criteria were COPD of grades II-III with pronounced clinical symptoms and infrequent exacerbations, according to the GOLD (2024) recommendations.

Results. The study revealed a progressive increase in systemic inflammation markers — the NLR (from 2.01 to 3.43) and PLR (from 132.0 to 247.0) indices, as well as CRP levels, and an imbalance in MMP-9/TIMP-1 (from 0.5 to 4.3), indicating a shift in the balance towards tissue destruction and fibrogenesis with increasing COPD severity. Correlation analysis revealed a statistically significant negative correlation of FEV1 with NLR, PLR, and MMP-9/TIMP-1, and a positive correlation between the MMP-9/TIMP-1 ratio and the NLR and PLR indices. This indicates that the aggravation of systemic inflammation and impaired proteolysis in COPD are interrelated processes.

Conclusion. NLR and PLR have proven their clinical significance for the stratification of COPD patients by disease severity. The identified increase in the MMP-9/TIMP-1 ratio indicates a shift towards fibrosis and shows promise for the objective diagnosis of the disease.

Key words: chronic obstructive pulmonary disease, systemic inflammation, MMP-9, TIMP-1.

 REFERENCES

1. Avdeyev S.N., Leshchenko I.V., Aysanov Z.R. Chronic obstructive pulmonary disease (COPD 2024). Clinical guidelines (short version). Respiratornaya meditsina, 2025, vol. 1, no. 2, pp. 5–16 (in Russ.).
2. Manoshkina E.M. Incidence of chronic obstructive pulmonary disease in the Russian Federation. Sotsial′nyye aspekty zdorov′ya naseleniya [setevoye izdaniye], 2025, vol. 71, no. 3, p. 4 (in Russ.), available at: http://vestnik.mednet.ru/content/view/1788/30/ lang,ru/ (accessed on: 28.10.2025). DOI: 10.21045/2071-5021-2025-71-3-4
3. Dimic-Janjic S., Hoda M.A., Milenkovic B. et al. The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity. Eur. J. Med. Res, 2023, vol. 28 (1), p. 127. DOI: 10.1186/s40001-023-01094-7
4. Li Y., Lu Y., Zhao Z. et al. Relationships of MMP-9 and TIMP-1 proteins with chronic obstructive pulmonary disease risk: A systematic review and meta-analysis. J. Res. Med. Sci, 2016, vol. 21 (12). DOI: 10.4103/1735-1995.178737
5. Cabral-Pacheco G.A., Garza-Veloz .I, Castruita-De la Rosa C. et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci, 2020, vol. 21 (24), p. 9739. DOI: 10.3390/ijms21249739
6. Uysal P., Uzun H. 6. relationship between circulating serpina3g, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 and -2 with chronic obstructive pulmonary disease severity. Biomolecules, 2019, vol. 9 (2), p. 62, available at: https://pubmed.ncbi.nlm.nih.gov/30781876/ DOI: 10.3390/biom9020062
7. Fu Y., Wang Y., Wang Y. et al. Biomarkers (NLR, PLR, SII) for frequent COPD exacerbations: diagnostic and clinical management implications in a retrospective study. Int. J. Chron. Obstruct. Pulmon. Dis, 2025, vol. 20, pp. 987–998. DOI :10.2147/COPD.S510118
8. Agustí A., Celli B.R., Criner G.J. et al. Global initiative for chronic obstructive lung disease 2023 report: GOLD executive summary. Eur. Respir. J, 2023, vol. 61 (4), r. 2300239. DOI: 10.1183/13993003.00239-2023
9. Liu X., Ge H., Feng X. et al. The combination of hemogram indexes to predict exacerbation in stable chronic obstructive pulmonary disease. Front. Med. (Lausanne), 2020, vol. 7, p. 572435. DOI: 10.3389/fmed.2020.572435
10. Ao T., Huang Y., Zhen P., Hu M. Association between c-reactive protein to lymphocyte ratio and chronic obstructive pulmonary disease: a cross-sectional study. Int. J. Chron. Obstruct. Pulmon. Dis, 2025, vol. 12 (20), pp. 1915–1925. DOI: 10.2147/COPD.S510755
11. Vasil′yeva L.V., Gosteva E.V., Suslova E.Yu. et al. Association of systemic inflammation with the severity of obstructive sleep apnea in elderly men with chronic obstructive pulmonary disease. Prakticheskaya meditsina (in Russ.), available at: https://www.elibrary.ru/item.asp?id=59952211 DOI: 10.32000/2072-1757-2024-1-53-57
12. Linder R., Rönmark E., Pourazar J. et al. Proteolytic biomarkers are related to prognosis in COPD- report from a population-based cohort. Respir. Res, 2018, vol. 19 (1), r. 64. DOI: 10.1186/s12931-018-0772-5
13. Vasil′yeva L.V., Gosteva E.V., Suslova E.Yu. et al. Pathogenetic mechanisms of the relationship between the association of biomarkers MMP-9 and TIMP-1 with the severity of chronic obstructive pulmonary disease. Farmateka, 2023, vol. 30, no. 9-10, pp. 116–121 (in Russ.). DOI: 10.18565/pharmateca.2023.9-10.116-121
14. Piesiak P., Brzecka A., Kosacka M. et al. Concentrations of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in serum of patients with chronic obstructive pulmonary disease. Pol. Merkur. Lekarski, 2011, vol. 31 (185), pp. 270–273.