Published ahead of print on January 16, 2009, doi:10.1164/rccm.200810-1534OC
© 2009 American Thoracic Society doi: 10.1164/rccm.200810-1534OC
Circulating Fibrocytes Are an Indicator of Poor Prognosis in Idiopathic Pulmonary Fibrosis1 Department of Medicine, McMaster University, and Firestone Institute for Respiratory Health, St. Joseph's Healthcare; 2 Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University; 3 Department of Diagnostic Imaging, McMaster University, and St. Joseph's Healthcare, Hamilton, Ontario, Canada; and 4 University of Virginia School of Medicine, Charlottesville, Virginia Correspondence and requests for reprints should be addressed to Martin R. J. Kolb, M.D., Ph.D., McMaster University, Firestone Institute for Respiratory Health, 50 Charlton Avenue East, Room T2121, Hamilton, ON, L8N 4A6 Canada. E-mail: kolbm{at}mcmaster.ca Rationale: 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. Objectives: 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. Measurements and Main 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.
Key Words: idiopathic pulmonary fibrosis • biomarker • fibroblast • fibrocyte
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