Enhanced Exhalation of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Patients with COPD Exacerbation: A Prospective Study

Abstract

Background: Matrix metalloproteinase-9 (MMP-9) and its inhibitor tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the pathogenesis of airway inflammation in patients with chronic obstructive pulmonary disease (COPD). However, no study so far has addressed their value as noninvasive biomarkers of airways inflammation. Objective: To evaluate MMP-9 and TIMP-1 concentrations in the exhaled breath condensate (EBC) of patients with stable COPD and also during the exacerbation episode. Methods: EBC and serum samples were collected in 17 stable-phase COPD patients who were current smokers as well as during their first exacerbation episode, and in 22 asymptomatic smokers. EBC and serum levels of MMP-9 and TIMP-1 were measured with ELISA kit. Results: Mean EBC MMP-9 and TIMP-1 levels were higher in patients with stable COPD than in asymptomatic smokers. Exacerbation of COPD increased 2-fold the exhalation of MMP-9 (18.5 ± 10.1 ng/ml vs. 8.9 ± 6.2 ng/ml, p = 0.01) and TIMP-1 (to 41.1 ± 20.4 ng/ml vs. 16.4 ± 6.8 ng/ml, p < 0.001). Both, MMP-9 and TIMP-1 in EBC correlated negatively with FEV₁ (% predicted) at baseline (r = –0.78, p < 0.001 and r = –0.73, p < 0.001) and during the exacerbation episode (r = –0.57, p = 0.02 and r = –0.65, p = 0.005). Similar negative correlations were noted with FVC (% predicted), except for MMP-9 in EBC at exacerbation. Exhaled MMP-9 and TIMP-1 did not correlate with serum concentrations in COPD patients, either at baseline or during exacerbation. Conclusion: Exhaled MMP-9 and TIMP-1 increased during COPD exacerbation and was negatively correlated with spirometric variables, which suggests the usefulness of their measurement in EBC for the monitoring of airways inflammation. However, to better assess their diagnostic or prognostic value larger studies are necessary.

FEV1 inversely correlates with metalloproteinases 1, 7, 9 and CRP in COPD by biomass smoke exposure

“…On the other hand, MMP-9 is inhibited by TIMP-1 and an imbalance in the MMP-9/TIMP-1 ratio could be involved in COPD pathogenesis. In this regard, Kang et al demonstrated a correlation among the increase in the MMP-9/TIMP-1 complex in lung tissue from smokers and the airflow obstruction observed [31] and Higashimoto et colleagues [20] found that circulating TIMP-1 concentration was significantly higher in stable COPD patients. This and our report suggest that excess amounts of TIMP-1 compared with those of MMP-9 may be related to airway narrowing.…”

Effect of Pingchuan Guben decoction on patients with chronic obstructive pulmonary disease: Results from a randomized comparative effectiveness research trial

“…The SLPI level is higher and is negatively correlated with FEV/FVC in patients with COPD (53). A prospective study proposed that the expression of TIMP-1 in exhaled breath condensate is higher in patients with stable COPD (54). The increased TIMP-1 expression is closely related with COPD exacerbation (54).…”

“…A prospective study proposed that the expression of TIMP-1 in exhaled breath condensate is higher in patients with stable COPD (54). The increased TIMP-1 expression is closely related with COPD exacerbation (54). In the present study, it was demonstrated that the levels of inflammation-related factors, including SP-D, PCT, sTREM-1, SAA, IP-10 and TRAIL, as well as protease molecules such as NE, α1-AT, SLPI and TIMP-1, were significantly ameliorated in the intervention group compared with the control group at 12 weeks.…”

The comparative characteristic of level of matrix metalloproteinase-9 and high-sensitive C-reactive protein indicators at comorbid course of arterial hypertension and chronic obstructive pulmonary disease

“…Матриксна металопро-теїназа-9 (ММП) грає важливу роль беручи участь в процесі патогенезу серцево-судинних захворю-вань, так само має достовірний кореляційний зв'язок з рівнем бронхіальної обструкції. У дослідженні Hurst R. et al була доведена висока чутливість та специфічність такого маркера запалення як вч-СРБ серед 36 біомаркерів, однак кращою комбінацією в порівнянні з одним цим маркером було визначення додатково тріади біомаркерів ММП-9, вч-СРБ, фак-тор інгібування мієлоїдних попередників [12,14,15]. Отримані результати досліджень демонструють ви-соку специфічність і чутливість маркерів запалення ММП-9 і вч-СРБ, проте враховуючи малу кількість досліджень при поєднанні ГХ та ХОЗЛ, потрібне подальше вивчення даної патології.…”