Lee Janet S, Rosengart Matthew R, Kondragunta Venkateswarlu, Zhang Yingze, McMurray Jessica, Branch Robert A, Choi Augustine M K, Sciurba Frank C
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Respir Res. 2007 Sep 14;8(1):64. doi: 10.1186/1465-9921-8-64.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome characterized by varying degrees of airflow limitation and diffusion impairment. There is increasing evidence to suggest that COPD is also characterized by systemic inflammation. The primary goal of this study was to identify soluble proteins in plasma that associate with the severity of airflow limitation in a COPD cohort with stable disease. A secondary goal was to assess whether unique markers associate with diffusion impairment, based on diffusion capacity of carbon monoxide (DLCO), independent of the forced expiratory volume in 1 second (FEV1).
A cross sectional study of 73 COPD subjects was performed in order to examine the association of 25 different plasma proteins with the severity of lung function impairment, as defined by the baseline measurements of the % predicted FEV1 and the % predicted DLCO. Plasma protein concentrations were assayed using multiplexed immunobead-based cytokine profiling. Associations between lung function and protein concentrations were adjusted for age, gender, pack years smoking history, current smoking, inhaled corticosteroid use, systemic corticosteroid use and statin use.
Plasma concentrations of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1), CCL4/macrophage inflammatory protein-1 beta (CCL4/MIP-1 beta), CCL11/eotaxin, and interleukin-13 (IL-13) were inversely associated with the % FEV1. Plasma concentrations of soluble Fas were associated with the % DLCO, whereas CXCL9/monokine induced by interferon-gamma (CXCL9/Mig), granulocyte- colony stimulating factor (G-CSF) and IL-13 showed inverse relationships with the % DLCO.
Systemic inflammation in a COPD cohort is characterized by cytokines implicated in inflammatory cell recruitment and airway remodeling. Plasma concentrations of IL-13 and chemoattractants for monocytes, T lymphocytes, and eosinophils show associations with increasing severity of disease. Soluble Fas, G-CSF and CXCL9/Mig may be unique markers that associate with disease characterized by disproportionate abnormalities in DLCO independent of the FEV1.
慢性阻塞性肺疾病（COPD）是一种异质性综合征，其特征为不同程度的气流受限和弥散功能障碍。越来越多的证据表明，COPD还具有全身炎症的特征。本研究的主要目的是在病情稳定的COPD队列中，确定与气流受限严重程度相关的血浆可溶性蛋白。次要目的是基于一氧化碳弥散量（DLCO），评估独立于1秒用力呼气量（FEV1）之外，是否有独特的标志物与弥散功能障碍相关。
对73例COPD受试者进行了一项横断面研究，以检查25种不同血浆蛋白与肺功能损害严重程度之间的关联，肺功能损害严重程度由预测FEV1百分比和预测DLCO百分比的基线测量值定义。使用基于多重免疫磁珠的细胞因子谱分析来测定血浆蛋白浓度。对肺功能与蛋白浓度之间的关联进行了年龄、性别、吸烟包年史、当前吸烟情况、吸入糖皮质激素使用情况、全身糖皮质激素使用情况和他汀类药物使用情况的校正。
血浆CCL2/单核细胞趋化蛋白-1（CCL2/MCP-1）、CCL4/巨噬细胞炎性蛋白-1β（CCL4/MIP-1β）、CCL11/嗜酸性粒细胞趋化因子和白细胞介素-13（IL-13）的浓度与FEV1百分比呈负相关。可溶性Fas的血浆浓度与DLCO百分比相关，而干扰素-γ诱导的CXCL9/单核细胞趋化蛋白（CXCL9/Mig）、粒细胞集落刺激因子（G-CSF）和IL-13与DLCO百分比呈负相关。
COPD队列中的全身炎症以与炎症细胞募集和气道重塑有关的细胞因子为特征。IL-13以及单核细胞、T淋巴细胞和嗜酸性粒细胞趋化因子的血浆浓度与疾病严重程度增加相关。可溶性Fas、G-CSF和CXCL9/Mig可能是与以独立于FEV1的DLCO不成比例异常为特征的疾病相关的独特标志物。
