title: Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis.
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 (&gt; 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.affiliation: Department of Pulmonary and Critical Care Medicine, Seoul, South Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Do
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colby
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.
authors.forename: Seungbong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Seoul, South Korea. Electronic address: dskim@amc.seoul.kr.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1; D037662:Pulmonary Surfactant-Associated Protein A; D020783:Matrix Metalloproteinase 7