• Hilary F Armstrong, Anna J Podolanczuk, R Graham Barr, Elizabeth C Oelsner, Steven M Kawut, Eric A Hoffman, Russell Tracy, Naftali Kaminski, Robyn L McClelland, and David J Lederer.
• 1 Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York.
• Am. J. Respir. Crit. Care Med. 2017 Nov 15; 196 (10): 1311-1317.

RationaleMatrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis.ObjectivesTo test associations between serum MMP-7 and lung function, respiratory symptoms, interstitial lung abnormalities (ILA), and all-cause mortality in community-dwelling adults sampled without regard to respiratory symptoms or disease.MethodsWe measured serum MMP-7 in 1,227 participants in MESA (Multi-Ethnic Study of Atherosclerosis) at baseline. The 5-year outcome data were available for spirometry (n = 697), cough (n = 722), and dyspnea (n = 1,050). The 10-year outcome data were available for ILA (n = 561) and mortality (n = 1,227). We used linear, logistic, and Cox regression to control for potential confounders.Measurements And Main ResultsThe mean (±SD) serum MMP-7 level was 4.3 (±2.5) ng/ml (range, 1.2-24.1 ng/ml). In adjusted models, each natural log unit increment in serum MMP-7 was associated with a 3.7% absolute decrement in FVC% (95% confidence interval [CI] = 0.9-6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI = 1.3-1.9), a 1.5-fold increased odds of ILAs (95% CI = 1.1-2.1), and a 2.2-fold increased all-cause mortality rate (95% CI = 1.9-2.5). The associations with ILA and mortality tended to be stronger among never-smokers (P values for interaction 0.06 and 0.01, respectively).ConclusionsSerum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.

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