title: Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  The clinical management of idiopathic pulmonary fibrosis (IPF) remains a major challenge due to lack of effective drug therapy or accurate indicators for disease progression. Fibrocytes are circulating mesenchymal cell progenitors that are involved in tissue repair and fibrosis.
  
  
  OBJECTIVE
  To test the hypothesis that assay of these cells may provide a biomarker for activity and progression of IPF.
  
  
  METHODS
  Fibrocytes were defined as cells positive for CD45 and collagen-1 by flow cytometry and quantified in patients with stable IPF and during acute exacerbation of the disease. We investigated the clinical and prognostic value of fibrocyte counts by comparison with standard clinical parameters and survival. We used healthy age-matched volunteers and patients with acute respiratory distress syndrome as control subjects.
  
  
  RESULTS
  Fibrocytes were significantly elevated in patients with stable IPF (n = 51), with a further increase during acute disease exacerbation (n = 7; P < 0.001 vs. control subjects). Patients with acute respiratory distress syndrome (n = 10) were not different from healthy control subjects or stable patients with IPF. Fibrocyte numbers were not correlated with lung function or radiologic severity scores, but they were an independent predictor of early mortality. The mean survival of patients with fibrocytes higher than 5% of total blood leukocytes was 7.5 months compared with 27 months for patients with less than 5% (P < 0.0001).
  
  
  CONCLUSIONS
  Fibrocytes are an indicator for disease activity of IPF and might be useful as a clinical marker for disease progression. This study suggests that quantification of circulating fibrocytes may allow prediction of early mortality in patients with IPF.
authors.affiliation: Department of Medicine, McMaster University, and Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, L8N 4A6 Canada.
authors.forename: Antje
authors.initials: A
authors.lastname: Moeller
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.forename: Kjetil
authors.initials: K
authors.lastname: Ask
authors.forename: Gerard
authors.initials: G
authors.lastname: Cox
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Margetts
authors.forename: Laszlo
authors.initials: L
authors.lastname: Farkas
authors.forename: Julian
authors.initials: J
authors.lastname: Dobranowski
authors.forename: Colm
authors.initials: C
authors.lastname: Boylan
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.forename: Martin
authors.initials: M
authors.lastname: Kolb
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000503:physiopathology; D017493:Leukocyte Common Antigens; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human