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Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis.
Chest. 2013 May; 143(5):1422-1429.Chest

Abstract

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.

Authors+Show Affiliations

Department of Pulmonary and Critical Care Medicine, Seoul, South Korea.Department of Radiology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ.Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.Department of Pulmonary and Critical Care Medicine, Seoul, South Korea. Electronic address: dskim@amc.seoul.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23715088

Citation

Song, Jin Woo, et al. "Blood Biomarkers MMP-7 and SP-A: Predictors of Outcome in Idiopathic Pulmonary Fibrosis." Chest, vol. 143, no. 5, 2013, pp. 1422-1429.
Song JW, Do KH, Jang SJ, et al. Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest. 2013;143(5):1422-1429.
Song, J. W., Do, K. H., Jang, S. J., Colby, T. V., Han, S., & Kim, D. S. (2013). Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest, 143(5), 1422-1429. https://doi.org/10.1378/chest.11-2735
Song JW, et al. Blood Biomarkers MMP-7 and SP-A: Predictors of Outcome in Idiopathic Pulmonary Fibrosis. Chest. 2013;143(5):1422-1429. PubMed PMID: 23715088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. AU - Song,Jin Woo, AU - Do,Kyung Hyun, AU - Jang,Se Jin, AU - Colby,Thomas V, AU - Han,Seungbong, AU - Kim,Dong Soon, PY - 2013/5/30/entrez PY - 2013/5/30/pubmed PY - 2013/8/30/medline SP - 1422 EP - 1429 JF - Chest JO - Chest VL - 143 IS - 5 N2 - 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. SN - 1931-3543 UR - https://www.unboundmedicine.com/medline/citation/23715088/Blood_biomarkers_MMP_7_and_SP_A:_predictors_of_outcome_in_idiopathic_pulmonary_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-3692(13)60342-6 DB - PRIME DP - Unbound Medicine ER -