Elevated MMP-9 tied to faster lung function decline, COPD development

An elevated matrix metalloproteinase-9 (MMP-9) appears to cause lung function decline and the development of chronic obstructive pulmonary disease (COPD), suggests a study.

This study consisted of two parts: a prospective cohort study that explored the association of circulating MMP-9 and respiratory health outcomes and a two-sample Mendelian randomization (MR) study that examined the causal effect between genetically predicted MMP-9 expression and lung function.

In the prospective cohort study, participants completed a questionnaire, spirometry, and chest CT, as well as provided blood samples at baseline. The authors conducted follow-up visits annually. Outcomes assessed were spirometry-defined COPD development, lung function decline, and exacerbations.

Of the 1,328 participants included in the baseline analysis, 1,034 (78 percent) completed the 2-year follow-up. Higher plasma MMP-9 at baseline correlated with chronic respiratory symptoms, severe emphysema, and air trapping.

At 2-year follow-up, each standard deviation increase in plasma MMP-9 resulted in faster decline in prebronchodilator FEV1 (adjusted difference, 6.4 mL/year, 95 percent confidence interval [CI], 0.7–12.1) and FVC (adjusted difference, 18.0 mL/year, 95 percent CI, 7.6–28.5), and higher exacerbation incidence.

Furthermore, higher plasma MMP-9 in participants with normal spirometry at baseline correlated with progression to spirometry-defined COPD (adjusted odds ratio, 1.93, 95 percent CI, 1.05–3.57).

In MR analysis, similar results toward negative associations of genetically predicted MMP-9 expression with FEV1 and FVC were observed.

“The longitudinal cohort and MR study provide evidence that MMP-9 might play a causative role in lung function decline and spirometry-defined COPD development,” the authors said.