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, David J. Lederer

Matrix metalloproteinase-7 (MMP-7) has been implicated in ILD pathobiology and proposed as a diagnostic and prognostic biomarker of IPF. To 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. We measured serum MMP-7 in 1,227 participants in the Multi Ethnic Study of Atherosclerosis at basline. Five-year outcome data was available for spirometry (n=697), cough (n=722), and dyspnea (n=1050). Ten-year outcome data was available for ILA (n=561) and mortality (n=1227). We used linear, logistic, and Cox regression to control for potential confounders. The mean ± SD serum MMP-7 level was 4.3 ± 2.5 ng/mL (range 1.2 to 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% CI 0.9 to 6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI 1.3 to 1.9), a 1.5-fold increased odds of ILAs (95% CI 1.1 to 2.1), and a 2.2-fold increased all-cause mortality rate (95% CI 1.9 to 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). Serum 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 ILD.