Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics.
Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics.
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通过PCR分层确定的痰液中的微生物组平衡会使COPD恶化，并显示出选择性使用抗生素的潜力。
DOI：
10.1371/journal.pone.0182833
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Barer MR
中科院分区：
文献类型：
--
作者：
Haldar K;Bafadhel M;Lau K;Berg A;Kwambana B;Kebadze T;Ramsheh MY;Barker B;Haldar P;Johnston S;Ketley JM;Brightling CE;Barer MR
虽然慢性阻塞性肺病（COPD）恶化的一部分患者明显受益于抗生素，但对其识别仍然具有挑战性。我们假设，对 COPD 痰样本中两个主要细菌群（Gammaproteobacteria (G) 和 Firmicutes (F)）之间的平衡进行选择性评估可能会揭示出一个亚群，该亚群在恶化时细菌群落结构发生变化，该变化在恢复时恢复到基线，并可能反映了有效的抗生素治疗。通过定量实时 PCR 确定系统发育特异性 16S rRNA 基因，以得出 66 个广泛表型 COPD 恶化事件的连续痰样本中的 G:F 比率。基于欧几里德距离测量的聚类分析，针对 66 次恶化发作的 4 次就诊时间（稳定日和恶化日：0,14 和 42）生成，揭示了命名为 HG、HF 和 GF 的三个亚组，反映了两个目标细菌群的优势或等效性。虽然其他亚组在恶化时没有显示任何变化，但 HG 簇 (n = 20) 的特点是 G:F 比率在恶化时显着增加，并在恢复时恢复到基线 (p<0.00001)； HG 组的比率也与炎症标志物呈正相关，与 FEV1 呈负相关。恶化时，G:F 显示出显着的受试者操作者特征曲线，可识别 HG 亚组（AUC 0.90，p<0.0001）。恶化时的 G:F 比率可以在与临床管理决策相一致的时间尺度上确定。我们认为 G:F 比率有潜力用作生物标志物，能够在 COPD 恶化中选择性使用抗生素，因此值得进一步的临床评估。
While a subgroup of patients with exacerbations of chronic obstructive pulmonary disease (COPD) clearly benefit from antibiotics, their identification remains challenging. We hypothesised that selective assessment of the balance between the two dominant bacterial groups (Gammaproteobacteria (G) and Firmicutes (F)) in COPD sputum samples might reveal a subgroup with a bacterial community structure change at exacerbation that was restored to baseline on recovery and potentially reflects effective antibiotic treatment. Phylogenetically specific 16S rRNA genes were determined by quantitative real time PCR to derive a G:F ratio in serial sputum samples from 66 extensively-phenotyped COPD exacerbation episodes. Cluster analysis based on Euclidean distance measures, generated across the 4 visit times (stable and exacerbation day: 0,14 and 42) for the 66 exacerbation episodes, revealed three subgroups designated HG, HF, and GF reflecting predominance or equivalence of the two target bacterial groups. While the other subgroups showed no change at exacerbation, the HG cluster (n = 20) was characterized by G:F ratios that increased significantly at exacerbation and returned to baseline on recovery (p<0.00001); ratios in the HG group also correlated positively with inflammatory markers and negatively with FEV1. At exacerbation G:F showed a significant receiver-operator-characteristic curve to identify the HG subgroup (AUC 0.90, p<0.0001). The G:F ratio at exacerbation can be determined on a timescale compatible with decisions regarding clinical management. We propose that the G:F ratio has potential for use as a biomarker enabling selective use of antibiotics in COPD exacerbations and hence warrants further clinical evaluation.
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影响因子：
11
作者：
Muhling, Martin;Woolven-Allen, John;Joint, Ian
通讯作者：
Joint, Ian
影响因子：
8.3
作者：
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24.3
作者：
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作者：
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DOI：
10.1164/rccm.201111-2075oc
发表时间：
2012-05-15
影响因子：
24.7
作者：
Sze, Marc A.;Dimitriu, Pedro A.;Hogg, James C.
通讯作者：
Hogg, James C.