Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Am J Respir Crit Care Med. 2011 Sep 15;184(6):662-71. doi: 10.1164/rccm.201104-0597OC.
Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.
Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.
Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated.
A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.
The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
慢性阻塞性肺疾病（COPD）的加重与炎症和病因有关，具有异质性。
研究 COPD 加重时生物标志物的表达，以确定生物标志物簇，并确定识别临床 COPD 加重表型的生物标志物，即与细菌、病毒或嗜酸性气道炎症相关的表型。
对 145 例 COPD 患者进行为期 1 年的稳定期和加重期随访。检测痰和血清中的生物标志物。通过聚合酶链反应和常规诊断细菌培养检测痰中的病毒和选定的细菌。使用无偏聚类分析探讨生物学表型，并研究区分临床加重表型的生物标志物。
共 145 例患者（101 例男性，44 例女性）纳入研究。86 例患者共发生 182 次加重。确定了 4 个不同的生物学加重簇。这些簇分别是细菌为主、病毒为主、嗜酸性粒细胞为主，以及第四个与炎症谱变化有限的簇称为“寡炎症”。所有加重中，55%、29%和 28%与细菌、病毒或痰嗜酸性粒细胞有关。能最好识别这些临床表型的生物标志物是痰 IL-1β，0.89（ROC 曲线下面积）（95%置信区间 [CI]，0.83-0.95）；血清 CXCL10，0.83（95% CI，0.70-0.96）；和外周血嗜酸性粒细胞百分比，0.85（95% CI，0.78-0.93）。
可以定义 COPD 加重时生物反应的异质性。痰 IL-1β、血清 CXCL10 和外周血嗜酸性粒细胞是 COPD 细菌、病毒或嗜酸性粒细胞相关加重的生物标志物。表型特异性生物标志物是否可以用于直接治疗值得进一步研究。
