期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 190, 期 8, 页码 906-913出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201403-0541OC
关键词
idiopathic pulmonary fibrosis; Muc5b; bacteria; microbiome
资金
- Asmarley Trust
- Wellcome Trust
- NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton
- Harefield NHS Foundation Trust
- AHSC Biomedical Research Centre at Imperial College London
- National Institutes of Health [HL097163, HL092870]
- GlaxoSmithKline
- Medical Research Council Program [G0600879]
- NIHR Clinical Lecturer funding scheme
- Pfizer UK
- Asthma UK [CH11SJ, MRC-AsthmaUKCentre] Funding Source: researchfish
- Medical Research Council [G0600879, G1000758] Funding Source: researchfish
- National Institute for Health Research [CL-2008-21-014] Funding Source: researchfish
- MRC [G0600879] Funding Source: UKRI
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.
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