Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Ann Thorac Surg. 2011 Aug;92(2):470-7; discussion 477. doi: 10.1016/j.athoracsur.2011.04.065.
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.
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.
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).
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.
肺移植后发生细支气管炎性闭塞综合征（BOS）会增加患者的发病率和死亡率。纤维细胞是循环骨髓源性间充质细胞祖细胞，可影响组织修复和纤维化。纤维细胞已被牵涉到慢性肺部炎症过程中。我们研究了循环纤维细胞数量与肺移植患者 BOS 发展的相关性。
我们前瞻性地定量检测了肺移植患者的循环纤维细胞水平。根据预测的 1 秒用力呼气量（FEV1），患者分为 BOS 组和非 BOS 组。以盲法分析纤维细胞活性（CD45+、胶原 1+）。
39 例患者（61.5%为男性）接受了双肺（33.3%）、左肺（25.6%）或右肺（41.0%）移植。BOS 组和非 BOS 组患者的平均年龄相似（58.3±3.9 岁 vs 60.3±2.0 岁，p=0.67）。慢性阻塞性肺疾病是肺移植最常见的适应证（41.0%）。FEV1 中位数在 BOS 组患者中低于非 BOS 组患者（1.08 升 vs 2.18 升/秒，p=0.001）。重要的是，与非 BOS 组患者相比，BOS 组患者的循环纤维细胞数量通过流式细胞术增加（8.91×10^5 个细胞/ml vs 2.96×10^5 个细胞/ml，p=0.03），且随着 BOS 分期的进展而逐渐增加（p=0.02）。
循环纤维细胞水平的升高与肺移植后 BOS 的发生相关，并与 BOS 分期的进展呈正相关。循环纤维细胞的定量检测可作为一种新的生物标志物，并可能成为肺移植患者 BOS 发生的治疗靶点。
