Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.

TitleLung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.
Publication TypeJournal Article
Year of Publication2014
AuthorsHan MLK, Zhou Y, Murray S, Tayob N, Noth I, Lama VN, Moore BB, White ES, Flaherty KR, Huffnagle GB, Martinez FJ
Corporate AuthorsCOMET Investigators
JournalLancet Respir Med
Volume2
Issue7
Pagination548-56
Date Published2014 Jul
ISSN Number2213-2619
KeywordsAdult, Aged, Aged, 80 and over, Disease Progression, Disease-Free Survival, DNA, Bacterial, Female, Follow-Up Studies, Humans, Idiopathic Pulmonary Fibrosis, Lung, Male, Microbiota, Middle Aged, Sequence Analysis, DNA, Staphylococcus, Streptococcus, Vital Capacity
Abstract

<p><b>BACKGROUND: </b>The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis.</p><p><b>METHODS: </b>Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a p<0.10. These OTUs were then used in the analysis of the principal components. The association between principal components and microbes with high factor loadings and progression-free survival were assessed with Cox regression analyses. The COMET study is registered with ClinicalTrials.gov, number NCT01071707.</p><p><b>FINDINGS: </b>Mean FVC was 70.1% (SD 17.0) and DLCO 42.3% (14.0) of predicted. Disease progression was significantly associated with increased relative abundance of two OTUs-Streptococcus OTU 1345 (relative risk 1.11, 95% CI 1.04-1.18; p=0.0009) and Staphylococcus OTU 1348 (1.16, 1.03-1.31, p=0.012). Thresholds for relative abundance of each OTU associated with progression-free survival were more than 3.9% for Streptococcus OTU 1345 (10.19, 2.94-35.35; p=0.0002) and more than 1.8% for Staphylococcus OTU 1348 (5.06, 1.71-14.93; p=0.003).</p><p><b>INTERPRETATION: </b>These preliminary data suggest progression of idiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association.</p><p><b>FUNDING: </b>National Institutes of Health.</p>

DOI10.1016/S2213-2600(14)70069-4
Alternate JournalLancet Respir Med
PubMed ID24767767
PubMed Central IDPMC4142525
Grant ListK23 HL093351 / HL / NHLBI NIH HHS / United States
R01 HL109118 / HL / NHLBI NIH HHS / United States
R01 HL115618 / HL / NHLBI NIH HHS / United States
RC2 HL101740 / HL / NHLBI NIH HHS / United States