Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
Respir Res. 2011 Nov 4;12(1):146. doi: 10.1186/1465-9921-12-146.
There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.
Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.
Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.
Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.
SCO104960, clinicaltrials.gov identifier NCT00292552.
需要生物标志物来更好地描述 COPD 患者，并帮助开发治疗干预措施。在 ECLIPSE 队列的一个亚组中评估了一组假定的血液生物标志物。
在 201 名 COPD 患者、37 名肺功能正常的前吸烟者对照者和 37 名来自 ECLIPSE 队列的健康非吸烟者中评估了 34 种血液生物标志物。使用基线和 3 个月样本评估生物标志物的可重复性。使用方差分析进行组间比较，通过 Bland-Altman 图评估可重复性，并使用 Spearman 相关系数评估生物标志物与临床特征之间的相关性。
与前吸烟者或非吸烟者对照者相比，15 种生物标志物在 COPD 患者中存在显著差异。一些生物标志物，如肿瘤坏死因子-α和干扰素-γ，仅在少数受试者中可测量，而其他生物标志物，如 C 反应蛋白，在 3 个月的复制期间显示出广泛的变异性。纤维蛋白原是最具可重复性的生物标志物，在 COPD 患者中与 6 分钟步行距离、恶化率、BODE 指数和 MRC 呼吸困难评分弱相关。在 3 个月的研究中，33%（66/201）的 COPD 患者至少有 1 次恶化，18%（36/201）的患者在 3 个月就诊后 30 天内报告恶化。在 3 个月就诊后 30 天内发生恶化的 COPD 患者中，CRP、纤维蛋白原、白细胞介素-6 和表面活性蛋白-D 显著升高，与未恶化或恶化已缓解的患者相比。
在基于气流阻塞（GOLD）诊断 COPD 的情况下，评估的生物标志物中只有少数可能对诊断或管理有用。对更有前途的生物标志物的进一步分析可能会揭示患者亚组的效用。纤维蛋白原特别从该队列中脱颖而出，是一种有潜在用途的生物标志物，需要进一步研究。
SCO104960，临床试验.gov 标识符 NCT00292552。
