痰液6基因表达特征可预测慢性阻塞性肺疾病的炎症表型及未来急性加重情况。
A Sputum 6 Gene Expression Signature Predicts Inflammatory Phenotypes and Future Exacerbations of COPD.
作者信息
Baines Katherine J, Negewo Netsanet A, Gibson Peter G, Fu Juan-Juan, Simpson Jodie L, Wark Peter A B, Fricker Michael, McDonald Vanessa M
机构信息
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
出版信息
Int J Chron Obstruct Pulmon Dis. 2020 Jul 2;15:1577-1590. doi: 10.2147/COPD.S245519. eCollection 2020.
BACKGROUND
The 6 gene expression signature (6GS) predicts inflammatory phenotype, exacerbation risk, and corticosteroid responsiveness in asthma. In COPD, patterns of airway inflammation are similar, suggesting the 6GS may be useful. This study determines the diagnostic and prognostic ability of 6GS in predicting inflammatory phenotypes and exacerbation risk in COPD.
METHODS
We performed 2 studies: a cross-sectional phenotype prediction study in stable COPD (total N=132; n=34 eosinophilic (E)-COPD, n=42 neutrophilic (N)-COPD, n=39 paucigranulocytic (PG)-COPD, n=17 mixed-granulocytic (MG)-COPD) that assessed 6GS ability to discriminate phenotypes (eosinophilia≥3%; neutrophilia≥61%); and a prospective cohort study (total n=54, n=8 E-COPD; n=18 N-COPD; n=20 PG-COPD; n=8 MG-COPD, n=21 exacerbation prone (≥2/year)) that investigated phenotype and exacerbation prediction utility. 6GS was measured by qPCR and evaluated using multiple logistic regression and area under the curve (AUC). Short-term reproducibility (intra-class correlation) and phenotyping method agreement (κ statistic) were assessed.
RESULTS
In the phenotype prediction study, 6GS could accurately identify and discriminate patients with E-COPD from N-COPD (AUC=96.4%; p<0.0001), PG-COPD (AUC=88.2%; p<0.0001) or MG-COPD (AUC=86.2%; p=0.0001), as well as N-COPD from PG-COPD (AUC=83.6%; p<0.0001) or MG-COPD (AUC=87.4%; p<0.0001) and was reproducible. In the prospective cohort study, 6GS had substantial agreement for neutrophilic inflammation (82%, κ=0.63, p<0.001) and moderate agreement for eosinophilic inflammation (78%, κ=0.42, p<0.001). 6GS could significantly discriminate exacerbation prone patients (AUC=77.2%; p=0.034). Higher levels were associated with poorer lung function and increased COPD severity.
CONCLUSION
6GS can significantly and reproducibly discriminate COPD inflammatory phenotypes and predict exacerbation prone patients and may become a useful molecular diagnostic tool assisting COPD management.
背景
6基因表达特征（6GS）可预测哮喘的炎症表型、急性加重风险和皮质类固醇反应性。在慢性阻塞性肺疾病（COPD）中，气道炎症模式相似，提示6GS可能有用。本研究确定6GS在预测COPD炎症表型和急性加重风险方面的诊断和预后能力。
方法
我们进行了两项研究：一项在稳定期COPD患者中开展的横断面表型预测研究（共132例；嗜酸性粒细胞性（E）-COPD 34例、中性粒细胞性（N）-COPD 42例、少粒细胞性（PG）-COPD 39例、混合粒细胞性（MG）-COPD 17例），评估6GS区分表型（嗜酸性粒细胞增多≥3%；中性粒细胞增多≥61%）的能力；以及一项前瞻性队列研究（共54例，E-COPD 8例、N-COPD 18例、PG-COPD 20例、MG-COPD 8例、易急性加重（≥2次/年）21例），调查表型和急性加重预测效用。通过定量聚合酶链反应（qPCR）测量6GS，并使用多因素逻辑回归和曲线下面积（AUC）进行评估。评估短期重复性（组内相关系数）和表型分析方法一致性（κ统计量）。
结果
在表型预测研究中，6GS能够准确识别并区分E-COPD与N-COPD患者（AUC = 96.4%；p < 0.0001）、PG-COPD患者（AUC = 88.2%；p < 0.0001）或MG-COPD患者（AUC = 86.2%；p = 0.0001），以及N-COPD与PG-COPD患者（AUC = 83.6%；p < 0.0001）或MG-COPD患者（AUC = 87.4%；p < 0.0001），且具有可重复性。在前瞻性队列研究中，6GS对中性粒细胞炎症具有高度一致性（82%，κ = 0.63，p < 0.001），对嗜酸性粒细胞炎症具有中度一致性（78%，κ = 0.42，p < 0.001）。6GS能够显著区分易急性加重患者（AUC = 77.2%；p = 0.034）。较高水平与较差的肺功能和更高的COPD严重程度相关。
结论
6GS能够显著且可重复地区分COPD炎症表型，并预测易急性加重患者，可能成为协助COPD管理的有用分子诊断工具。
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