[HTML][HTML] Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene
JM Wells, MM Parker, RA Oster, RP Bowler… - JCI insight, 2018 - ncbi.nlm.nih.gov
JCI insight, 2018•ncbi.nlm.nih.gov
BACKGROUND. Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung
remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that
elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset
of individuals with COPD with an inflammatory phenotype who are at increased risk for acute
exacerbation (AECOPD). METHODS. We analyzed Subpopulations and Intermediate
Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD …
remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that
elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset
of individuals with COPD with an inflammatory phenotype who are at increased risk for acute
exacerbation (AECOPD). METHODS. We analyzed Subpopulations and Intermediate
Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD …
Abstract
BACKGROUND. Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD).
METHODS. We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on> 95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts.
RESULTS. Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%–16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0–0.74] versus 0 [0–0.80] events/year and 0.9 [0.5–2] versus 0.5 [0–1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95% CI, 1.00–2.90; and OR, 3.03; 95% CI, 1.02–9.01), frequency (incidence rate ratio [IRR], 1.45; 95% CI, 1.23–1.7; and IRR, 1.24; 95% CI, 1.03–1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively.
CONCLUSIONS. Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD.
TRIAL REGISTRATION. ClinicalTrials. gov:
NCT01969344 (SPIROMICS) and
NCT00608764 (COPDGene).
FUNDING. This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01
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