Hurst John R, Donaldson Gavin C, Perera Wayomi R, Wilkinson Tom M A, Bilello John A, Hagan Gerry W, Vessey Rupert S, Wedzicha Jadwiga A
Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Am J Respir Crit Care Med. 2006 Oct 15;174(8):867-74. doi: 10.1164/rccm.200604-506OC. Epub 2006 Jun 23.
This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events.
The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers.
To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity.
We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD.
To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways.
Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.
本研究探讨了在慢性阻塞性肺疾病（COPD）急性加重期测量血浆生物标志物的应用，为这些重要事件的潜在发病机制提供了见解。
在COPD中，使用测量C反应蛋白（CRP）来确认急性加重或评估急性加重严重程度尚不清楚。此外，尚不清楚是否可能存在更有用的全身生物标志物。
评估血浆生物标志物在确认急性加重和预测急性加重严重程度方面的应用。
我们评估了90例COPD患者的90对基线和急性加重期血浆样本中的36种生物标志物。急性加重的诊断符合医疗保健使用和基于症状的标准。生物标志物浓度与急性加重严重程度的临床指标相关。检查生物标志物之间的相互关系，以获取有关COPD急性加重期全身炎症机制的信息。
为了确认急性加重的诊断，最具选择性的生物标志物是CRP。然而，单独使用它既不够敏感也不够特异（受试者工作特征曲线下面积[AUC]，0.73；95%置信区间，0.66-0.80）。CRP与患者当天记录的任何一项主要急性加重症状（呼吸困难、痰液量或痰液脓性）相结合，可将AUC显著提高至0.88（95%置信区间，0.82-0.93；p<0.0001）。生物标志物浓度与急性加重严重程度的临床指标之间无显著关系。生物标志物之间的相互关系表明，急性期反应分别与单核细胞和淋巴细胞-中性粒细胞途径有关。
在存在主要急性加重症状的情况下，血浆CRP浓度有助于确认COPD急性加重。全身生物标志物对预测急性加重严重程度无帮助。急性加重期的急性期反应与单核细胞功能指标最密切相关。
