Circulating Fibrocytes Are an Indicator of Poor Prognosis in Idiopathic Pulmonary Fibrosis

被引:374
作者
Moeller, Antje [2 ]
Gilpin, Sarah E. [3 ]
Ask, Kjetil [2 ,3 ]
Cox, Gerard [2 ]
Cook, Deborah [2 ]
Gauldie, Jack [3 ]
Margetts, Peter J. [2 ,3 ]
Farkas, Laszlo [2 ]
Dobranowski, Julian [4 ]
Boylan, Colm [4 ]
O'Byrne, Paul M. [2 ]
Strieter, Robert M. [5 ]
Kolb, Martin [1 ,2 ,3 ]
机构
[1] McMaster Univ, Firestone Inst Resp Hlth, Dept Med, Hamilton, ON L8N 4A6, Canada
[2] St Josephs Healthcare, Firestone Inst Resp Hlth, Hamilton, ON, Canada
[3] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON L8N 4A6, Canada
[4] McMaster Univ, Dept Diagnost Imaging, Hamilton, ON L8N 4A6, Canada
[5] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA
关键词
idiopathic pulmonary fibrosis; biomarker; fibroblast; fibrocyte; FIBROTIC INTERSTITIAL PNEUMONIA; PERIPHERAL-BLOOD FIBROCYTES; ACUTE EXACERBATION; BONE-MARROW; PROGENITOR CELLS; 6-MINUTE WALK; LUNG INJURY; RESOLUTION; SURVIVAL; REPAIR;
D O I
10.1164/rccm.200810-1534OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:588 / 594
页数:7
相关论文
共 46 条
[1]   Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites [J].
Abe, R ;
Donnelly, SC ;
Peng, T ;
Bucala, R ;
Metz, CN .
JOURNAL OF IMMUNOLOGY, 2001, 166 (12) :7556-7562
[2]   Cells derived from the circulation contribute to the repair of lung injury [J].
Abe, S ;
Boyer, C ;
Liu, XD ;
Wen, FQ ;
Kobayashi, T ;
Fang, QH ;
Wang, XQ ;
Hashimoto, M ;
Sharp, JG ;
Rennard, SI .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 170 (11) :1158-1163
[3]   Acute exacerbation of idiopathic pulmonary fibrosis: A systematic review [J].
Agarwal, Ritesh ;
Jindal, Surinder K. .
EUROPEAN JOURNAL OF INTERNAL MEDICINE, 2008, 19 (04) :227-235
[4]  
Aiba S, 1997, J CUTAN PATHOL, V24, P65
[5]   Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis [J].
Andersson-Sjoland, Annika ;
de Alba, Carolina Garcia ;
Nihlberg, Kristian ;
Becerril, Carina ;
Ramirez, Remedios ;
Pardo, Annie ;
Westergren-Thorsson, Gunilla ;
Selman, Moises .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (10) :2129-2140
[6]  
[Anonymous], 2002, Am J Respir Crit Care Med, DOI [10.1164/ajrccm.165.2.ats01, DOI 10.1164/AJRCCM.165.2.ATS01]
[7]   CIRCULATING FIBROCYTES DEFINE A NEW LEUKOCYTE SUBPOPULATION THAT MEDIATES TISSUE-REPAIR [J].
BUCALA, R ;
SPIEGEL, LA ;
CHESNEY, J ;
HOGAN, M ;
CERAMI, A .
MOLECULAR MEDICINE, 1994, 1 (01) :71-81
[8]   Acute exacerbations of idiopathic pulmonary fibrosis [J].
Collard, Harold R. ;
Moore, Bethany B. ;
Flaherty, Kevin R. ;
Brown, Kevin K. ;
Kaner, Robert J. ;
King, Talmadge E., Jr. ;
Lasky, Joseph A. ;
Loyd, James E. ;
Noth, Imre ;
Olman, Mitchell A. ;
Raghu, Ganesh ;
Roman, Jesse ;
Ryu, Jay H. ;
Zisman, David A. ;
Hunninghake, Gary W. ;
Colby, Thomas V. ;
Egan, Jim J. ;
Hansell, David M. ;
Johkoh, Takeshi ;
Kaminski, Naftali ;
Kim, Dong Soon ;
Kondoh, Yasuhiro ;
Lynch, David A. ;
Mueller-Quernheim, Joachim ;
Myers, Jeffrey L. ;
Nicholson, Andrew G. ;
Selman, Moises ;
Toews, Galen B. ;
Wells, Athol U. ;
Martinez, Fernando J. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 176 (07) :636-643
[9]   Future research directions in idiopathic pulmonary fibrosis - Summary of a National Heart, Lung, and Blood Institute working group [J].
Crystal, RG ;
Bitterman, PB ;
Mossman, B ;
Schwarz, MI ;
Sheppard, D ;
Almasy, L ;
Chapman, HA ;
Friedman, SL ;
King, TE ;
Leinwand, LA ;
Liotta, L ;
Martin, GR ;
Schwartz, DA ;
Schultz, GS ;
Wagner, CR ;
Musson, RA .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2002, 166 (02) :236-246
[10]   Six-minute walk, maximal exercise tests - Reproducibility in fibrotic interstitial pneumonia [J].
Eaton, T ;
Young, P ;
Milne, D ;
Wells, AU .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (10) :1150-1157