期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 195, 期 12, 页码 1640-1650出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201607-1408OC
关键词
usual interstitial pneumonia; acute lung injury; microbiome; idiopathic pulmonary fibrosis; expression
资金
- Asmarley Charitable Trust
- Wellcome Trust
- National Institute for Health Research (NIHR) [CS-2013-13-017]
- NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust
- Academic Health Science Centre Biomedical Research Centre at Imperial College London
- National Institutes of Health [HL097163, HL092870]
- GlaxoSmithKline
- Asthma UK [MRC-Asthma UK Centre, MRC-AsthmaUKCentre] Funding Source: researchfish
- British Lung Foundation [BLF-RMF15-16] Funding Source: researchfish
- Medical Research Council [G1000758] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10126] Funding Source: researchfish
Rationale: Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown. Objectives: To explore the host microbial interactions in IPF. Methods: Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays. Measurements and Main Results: By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease. Conclusions: Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up,, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据