The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis
The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis
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DOI：
10.1164/rccm.201403-0541oc
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发表时间：
2014-10-15
影响因子：
24.7
通讯作者：
Moffatt, Miriam F.
中科院分区：
文献类型：
--
作者：
Molyneaux, Phillip L.;Cox, Michael J.;Moffatt, Miriam F.
基本原理：特发性肺纤维化（IPF）是一种原因不明的进行性肺部疾病，可导致呼吸衰竭，并在诊断后5年内死亡。明显的呼吸道感染和免疫抑制具有较高的发病率和死亡率，与上皮完整性和宿主防御相关的基因多态性易患IPF。目的：探讨细菌在IPF发病和进展中的作用。我们前瞻性招募了根据国际标准诊断为IPF的患者以及健康吸烟者、非吸烟者，以中度慢性阻塞性肺疾病患者为对照组。受试者接受支气管肺泡灌洗（BAL），从中分离基因组DNA。扩增细菌16 S rRNA基因的V3-V5区域，允许细菌负荷的定量和鉴定的社区由16 S rRNA定量聚合酶链反应和焦磷酸测序。测量和主要结果：65例IPF患者的BAL液中的细菌的负担是44例对照组的两倍。基线细菌负荷可预测肺容量下降率和死亡风险，并与MUC 5 B粘蛋白基因rs35705950多态性（一种已证实的IPF宿主易感因素）独立相关。测序从所有受试者中获得了912，883个高质量读数。我们鉴定了嗜血杆菌、链球菌、奈瑟菌和韦荣球菌。在病例组中比对照组更丰富。回归分析表明，这些特定的操作分类单位以及细菌负荷独立与IPF.Conclusions：IPF的特点是在BAL中的细菌负荷增加，预测肺功能下降和死亡。需要进行抗菌治疗试验以确定微生物负荷是否是疾病的致病因素。
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and immunosuppression carry a high morbidity and mortality, and polymorphisms in genes related to epithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesis and progression of IPF.Methods: We prospectively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, nonsmokers, and subjects with moderate chronic obstructive pulmonary disease as control subjects. Subjects underwent bronchoalveolar lavage (BAL), from which genomic DNA was isolated. The V3-V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA quantitative polymerase chain reaction and pyrosequencing.Measurements and Main Results: Sixty-five patients with IPF had double the burden of bacteria in BAL fluid compared with 44 control subjects. Baseline bacterial burden predicted the rate of decline in lung volume and risk of death and associated independently with the rs35705950 polymorphism of the MUC5B mucin gene, a proven host susceptibility factor for IPF. Sequencing yielded 912,883 high-quality reads from all subjects. We identified Haemophilus,Streptococcus,Neisseria, and Veillonella spp. to be more abundant in cases than control subjects. Regression analyses indicated that these specific operational taxonomic units as well as bacterial burden associated independently with IPF.Conclusions: IPF is characterized by an increased bacterial burden in BAL that predicts decline in lung function and death. Trials of antimicrobial therapy are needed to determine if microbial burden is pathogenic in the disease.