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Original Research: Diffuse Lung Disease |

Blood Biomarkers MMP-7 and SP-APrognostic Value of Blood Biomarkers: Predictors of Outcome in Idiopathic Pulmonary Fibrosis

Jin Woo Song, MD; Kyung Hyun Do, MD; Se Jin Jang, MD; Thomas V. Colby, MD; Seungbong Han, PhD; Dong Soon Kim, MD
Author and Funding Information

From the Department of Pulmonary and Critical Care Medicine (Drs Song and Kim), Department of Radiology (Dr Do), Department of Pathology (Dr Jang), and Department of Clinical Epidemiology and Biostatistics (Dr Han), Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; Department of Laboratory Medicine and Pathology (Dr Colby), Mayo Clinic, Scottsdale, AZ.

Correspondence to: Dong Soon Kim, MD, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Asanbyungwon-gil, Songpa-gu, Seoul, South Korea; e-mail: dskim@amc.seoul.kr


Funding/Support: This study was supported by grant number 2010-495 from the Asan Institute for Life Sciences, Seoul, South Korea.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(5):1422-1429. doi:10.1378/chest.11-2735
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Background:  Because of the variable course of idiopathic pulmonary fibrosis (IPF), it is important to generate an accurate prognosis at the time of diagnosis. The aim of this study was to investigate the prognostic value of blood biomarkers in IPF.

Methods:  The plasma level of the biomarkers, matrix metalloproteinase-7 (MMP-7), Krebs von den Lungen-6 antigen, and surfactant protein (SP)-A and SP-D were retrospectively compared with the clinical course of 118 patients with IPF, 68 of whom had biopsy-proven IPF.

Results:  The median follow-up period was 24 months. Multivariate Cox analysis showed MMP-7 (HR, 1.056; P = .0063) and SP-A (HR, 1.011; P = .0001) were significant predictors of survival along with age, FVC, and extent of honeycombing. The patients with high levels of both MMP-7 (≥ 12.1 ng/mL) and SP-A (≥ 80.3 ng/mL) had shorter survival (1-year survival rate: 59%) and higher frequency (42%) of lung function decline (> 10% reduction in FVC in 6 months) compared with those with high levels of one biomarker (1-year survival rate: 81%; FVC decline: 27%) or low levels of both (1-year survival rate: 83.3%; FVC decline: 9%). Multivariate models demonstrated marginal improvement in the prediction of mortality (concordance index [C-index]: 0.731; P = .061) when MMP-7 and SP-A were included and compared with standard clinical predictors only (C-index: 0.686); however, it became significant with addition of MMP-7, SP-A, and Krebs von den Lungen-6 antigen (C-index: 0.730; P = .037).

Conclusions:  Our retrospective study suggested that at least three biomarkers are necessary to improve predictability of mortality in IPF compared with clinical parameters. Further study in a greater number of patients is warranted.


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