Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.
Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.
复制标题
DOI：
10.1016/s2213-2600(14)70069-4
复制
发表时间：
2014-07
影响因子：
76.2
通讯作者：
Martinez, Fernando J.
中科院分区：
文献类型：
--
作者：
Han, MeiLan K.;Zhou, Yueren;Murray, Susan;Tayob, Nabihah;Noth, Imre;Lama, Vibha N.;Moore, Bethany B.;White, Eric S.;Flaherty, Kevin R.;Huffnagle, Gary B.;Martinez, Fernando J.
肺部微生物组对IPF发病机制的贡献尚不清楚。使用COMET-IPF（将结局与生化标志物相关联以估计特发性肺纤维化的时间进展），本研究的目的是确定独特的微生物特征是否与疾病进展相关。诊断后4年内的35-80岁IPF受试者有资格入选。对受试者进行了最长80周的随访。这项已完成的观察性研究在ClinicalTrials.gov上注册，编号为NCT 01071707。无进展生存期定义为死亡、急性加重、肺移植或FVC下降10%或DLCO下降15%。454焦磷酸测序用于基于3%序列分歧分配操作分类单位（OTU）。校正的考克斯模型鉴定了OTU与无进展存活显著相关，p<0·10水平。然后将这些OTU用于主成分（PC）分析。通过考克斯回归分析检查PC和微生物与PC分析的高因子负荷和无进展生存期之间的关联。平均FVC为70.1%，平均DLCO为42.3%。通过PC分析鉴定的两种OTU（链球菌OTU）的相对丰度%增加，注意到与疾病进展的显著关联。（p<0.0009）和葡萄球菌属OTU（p= 0.01）。使用PC与单独使用两个OTU的关联强度相似。阈值分析有助于定义与无进展生存期相关的每种OTU的%相对丰度的临界点，链球菌OTU> 3.9%，HR 10.19（95%CI 2.94，35.35; p= 0.0002），葡萄球菌OTU> 1.8%，HR 5.06（1.71，14.93; p= 0.003）。这些初步数据表明，IPF疾病进展与葡萄球菌和链球菌属内特定成员的存在相关。
The lung microbiome’s contribution to IPF pathogenesisis unknown. Using COMET-IPF (Correlating Outcomes with biochemical Markers to Estimate Time-progression in Idiopathic Pulmonary Fibrosis), the goal of this study was to determine whether unique microbial signatures would associate with disease progression. IPF subjects within four years of diagnosis aged 35–80 were eligible for inclusion. Subjects were followed for up to a maximum of 80 weeks. This completed observational study is registered with ClinicalTrials.gov, number NCT01071707. Progression-free survival was defined as death, acute exacerbation, lung transplant, or decline in FVC of 10% or DLCO of 15%.DNA was isolated from 55 bronchoscopic alveolar lavage (BAL) samples. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) based on a 3% sequence divergence. Adjusted Cox models identified OTUs significantly associated with progression-free survival at a p<0·10 level. These OTUs were then used in principal components (PC) analysis. The association between PCs and microbes with high factor loadings from the PC analysis and progression-free survival were examined via Cox regression analyses. Mean FVC was 70·1% and mean DLCO 42·3 %predicted. Significant associations with disease progression were noted with increased % relative abundance of two OTUs identified by PC analysis, a Streptococcus OTU. (p<0·0009) and a Staphylococcus OTU(p=0·01). Strength of associations using PCs versus two OTUs alone was similar. Threshold analysis helped define a cut point for % relative abundance for each OTU associated with progression-free survival, >3·9% for the Streptococcus OTU, HR 10·19 (95% CI 2·94, 35·35; p=0·0002) and >1·8% for the Staphylococcus OTU, HR 5·06 (1·71, 14·93; p=0·003). These preliminary data suggest IPF disease progression is associated with presence of specific members within the Staphylococcus and Streptococcus genera.