Department of Biomarker Development, Nycomed GmbH, Konstanz, Germany.
PLoS One. 2012;7(10):e46207. doi: 10.1371/journal.pone.0046207. Epub 2012 Oct 4.
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, primarily affecting the airways. Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions. We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II) matched for age and gender. Sample collection was performed twice within a period of 6 weeks. Assays for over 100 different markers were validated for the respective matrices prior to analysis. In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6), most of these in serum. Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor) and confirms (e.g. C-reactive-protein, interleukin-6) previous findings. No correlations between lung and serum markers were observed, including A1AT. Airway inflammation defined by sputum neutrophils showed only a moderate repeatability. This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers. These results are relevant for ongoing large clinical trials and future COPD research. While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways.
慢性阻塞性肺疾病（COPD）是一种慢性炎症性疾病，主要影响气道。需要稳定的生物标志物来描述疾病的炎症表型，这些标志物与疾病活动相关，适合预测疾病进展，以监测药物干预的疗效和安全性。因此，我们分析了 23 名健康吸烟者和 24 名吸烟 COPD 患者（GOLD II）支气管肺泡灌洗液、支气管活检、血清和诱导痰中的大量标志物，这些患者在年龄和性别上相匹配。在 6 周的时间内分两次进行样本采集。在进行分析之前，针对各基质对超过 100 种不同标志物的检测进行了验证。在我们的研究中，我们发现了 51 种具有足够可重复性的标志物（组内相关系数>0.6），其中大多数在血清中。所有部位的标志物均观察到组间差异，这扩展（von-Willebrand 因子）并证实（例如 C 反应蛋白、白细胞介素-6）了之前的发现。未观察到肺和血清标志物之间存在相关性，包括 A1AT。通过痰中性粒细胞定义的气道炎症仅具有中等的可重复性。当使用中性粒细胞和四个痰液相标志物的组合来定义炎症表型时，这种情况可以得到改善。总之，我们的研究提供了关于 COPD 相关肺和系统性标志物的可重复性和相互关系的全面信息。这些结果与正在进行的大型临床试验和未来的 COPD 研究相关。虽然血清标志物可以区分有和没有 COPD 的吸烟者，但它们似乎不能充分反映气道中与疾病相关的炎症过程。
