title: Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker.
abstract: BACKGROUND
  Development of bronchiolitis obliterans syndrome (BOS) after lung transplantation confers increased patient morbidity and mortality. Fibrocytes are circulating bone marrow-derived mesenchymal cell progenitors that influence tissue repair and fibrosis. Fibrocytes have been implicated in chronic pulmonary inflammatory processes. We investigated the correlation of circulating fibrocyte number with BOS development in lung transplant patients.
  
  
  METHODS
  We prospectively quantified circulating fibrocyte levels among lung transplant patients. Patients were stratified according to the development of BOS as indicated by predicted forced expiratory volume in 1 second. Fibrocyte activity was analyzed by flow cytometry (cluster of differentiation 45+, collagen 1+) in a blinded manner related to clinical presentation.
  
  
  RESULTS
  Thirty-nine patients (61.5% men) underwent double (33.3%), left (25.6%), or right (41.0%) lung transplantation. Average patient age was similar between BOS and non-BOS patients (58.3±3.9 vs 60.3±2.0 years, p=0.67). Chronic obstructive lung disease was the most common indication for lung transplantation (41.0%). Median forced expiratory volume in 1 second was lower among BOS patients compared with non-BOS patients (1.08 vs. 2.18 L/s, p=0.001). Importantly, circulating fibrocyte numbers were increased in BOS patients compared with non-BOS patients (8.91 vs 2.96×10(5) cells/mL, p=0.03) by flow cytometry and were incrementally increased with advancing BOS stage (p=0.02).
  
  
  CONCLUSIONS
  Increased circulating fibrocyte levels correlate with the development of BOS after lung transplantation and positively correlate with advancing BOS stage. Quantification of circulating fibrocytes could serve as a novel biomarker and possible therapeutic target for BOS development in lung transplant patients.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: LaPar
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.forename: Abbas
authors.initials: A
authors.lastname: Emaminia
authors.forename: David A
authors.initials: DA
authors.lastname: Harris
authors.forename: Brett A
authors.initials: BA
authors.lastname: Strieter
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Robbins
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lau
mesh_terms: D000199:Actins / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000473:pathology*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D024042:Collagen Type I / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood*; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis* / Q000473:pathology*; D011379:Prognosis; D054400:Receptors, CCR7 / Q000097:blood; D019718:Receptors, CXCR4 / Q000097:blood
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D015415:Biomarkers; C515370:CCR7 protein, human; C527276:CXCR4 protein, human; D024042:Collagen Type I; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human