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. 2011 Aug;92(2):470-7; discussion 477.
doi: 10.1016/j.athoracsur.2011.04.065.

Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker

Damien J LaPar  1 , Marie D Burdick, Abbas Emaminia, David A Harris, Brett A Strieter, Ling Liu, Mark Robbins, Irving L Kron, Robert M Strieter, Christine L Lau
Affiliations

Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker

Damien J LaPar et al. Ann Thorac Surg. 2011 Aug.

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.

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Figures

Figure 1
Figure 1
Representative flow cytometric analysis of circulating fibrocytes for a lung transplant patient without bronchiolitis obliterans (A-C) compared to a patient with bronchiolitis obliterans development (D-F). (A) Positive population of CD45 cells in patient without BOS. (B) Isotype control for collagen-1 set on CD45-gated cell population in patient without BOS. (C) Positive population for CD45 and collagen-1 cells in patient without BOS. (D) Positive population of CD45 cells in patient with BOS. (E) Isotype control for collagen-1 set on CD45-gated cell population in patient with BOS. (F) Increased positive population for CD45 and collagen-1 cells in patient with BOS. FITC=fluorescein isothiocyanate; SSC-A=side scatter.
Figure 2
Figure 2
Circulating fibrocytes among lung transplant patients with and without bronchiolitis obliterans development. (A) Represents number of CD45+collagen-1+ cells. (B) Represents number of CD45+collagen-1+CXCR4+ cells. (C) Represents number of CD45+collagen-1+CCR7+ cells. (D) Represents number of CD45+collagen-1+CD34+ cells. Box and whiskers represent 25–75th and 10–90th percentiles, respectively; transverse lines represent median. BOS=bronchiolitis obliterans; *p<0.05 for independent samples comparison to no BOS development.
Figure 3
Figure 3
Circulating fibrocytes among lung transplant patients by bronchiolitis obliterans stage. No BOS (n=29), Stage I (n=3), Stage II (n=3), Stage III (n=4). Results represent mean ± standard error. BOS=bronchiolitis obliterans; *p<0.05 vs. all other groups.
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