Features of the extracellular matrix state in the development of copd in the high-risk category of exacerbations

Objective: to assess the concentration of extracellular matrix markers MMP-2, MMP-9 and their tissue inhibitors TIMP-1, TIMP-2 in the development of COPD of the high-risk category of exacerbations.

Materials and methods: 148 patients with COPD of the high-risk category of exacerbations were examined, 114 of them were men (77%) and 34 were women (23%), the average age was 64.41 ± 6.72 years. Two study groups were identified: the first group consisted of 75 patients with a predominantly bronchitic phenotype of the disease: 61 men (81%) and 14 women (19%) aged 44 to 72 years (average age 64.0 ± 7.8 years); the second group consisted of 73 patients with a predominantly emphysematous phenotype: 56 men (77%) and 17 women (23%) aged 54 to 72 years (average age 64.4 ± 6.7 years). The concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were assessed in the development of COPD in the high-risk category of exacerbations and compared with the clinical phenotype of the disease by the "sandwich" ELISA method, the indicators of the control group (healthy) were used as the norm.

Results: the development of COPD in the high-risk category of exacerbations is accompanied by an increase in the concentration of MMP-2 and MMP-9 against the background of a pronounced imbalance of the antiprotease system in favor of proproteolytic activity with insufficient production of TIMP-1 and inhibition of TIMP-2 production. In the bronchitic phenotype, an increase in the concentration of MMP-9 from 557 ng/ml to 1356 ng/ml, MMP-2 from 198 ng/ml to 213 ng/ml is detected against the background of insufficient production of TIMP-1 (less than 352.5 ng/ml) and inhibition of production of TIMP-2 (less than 98 ng/ml). The emphysematous phenotype is associated with high elastolytic activity of MMP-9 (1357 ng/ml and higher) and MMP-2 (214 ng/ml and higher) against the background of an increasing deficiency of tissue inhibitors. A high (90%) diagnostic significance of the MMP-2 level for the differentiation of phenotypes was determined. Conclusion: with the development of COPD with frequent exacerbations, pronounced elastolytic activity is noted, which is most pronounced in patients with a predominantly emphysematous phenotype. For the purpose of differential diagnosis of clinical phenotypes in patients with COPD of the high–risk category of exacerbations, it is necessary to use the concentration of MMP-2 with a threshold value of more than 214 ng/ml as a laboratory criterion for a predominantly emphysematous phenotype.

Conclusion: With the development of COPD with frequent exacerbations, pronounced elastolytic activity is noted, which is most pronounced in patients with a predominantly emphysematous phenotype. For the purpose of differential diagnosis of clinical phenotypes in patients with COPD of the high–risk category of exacerbations, it is necessary to use the concentration of MMP-2 with a threshold value of more than 214 ng/ml as a laboratory criterion for a predominantly emphysematous phenotype.

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