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

Abstract

Background 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. Methods 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. Findings 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). Interpretation These preliminary data suggest IPF disease progression is associated with presence of specific members within the Staphylococcus and Streptococcus genera.

Long-term macrolides in diffuse interstitial lung diseases

“…Although the most frequently isolated bacterial species (Prevotella, Veillonella and Escherichia) coincided in part with those identified by MOLYNEAUX et al [25], the authors also observed a new element: a strong association between the presence of specific species of Streptococcus and Staphylococcus and disease progression [28].…”

“…Using the data from the COMET-IPF study (Correlating Outcomes with Biochemical Markers to Estimate Time-progression in Idiopathic Pulmonary Fibrosis), HAN et al [28] retrospectively evaluated the role of the microbiota in disease progression. Although the most frequently isolated bacterial species (Prevotella, Veillonella and Escherichia) coincided in part with those identified by MOLYNEAUX et al [25], the authors also observed a new element: a strong association between the presence of specific species of Streptococcus and Staphylococcus and disease progression [28].…”

Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm

“…The risk of infection can be reduced by standard infection control measures such as hand washing and vaccination against influenza and pneumococcus. Specific members of the Streptococcus and Staphylococcus genera are associated with IPF progression [69], and the role of the lung microbiome in AE-IPF requires further study. Anti-acid therapy may slow IPF progression and reduce the risk of acute respiratory worsening secondary to aspiration [70], particularly in patients that have subjective symptoms or objective evidence of acid reflux.…”

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

“…This new characterization of the lung microbiome is likely to provide important pathogenic insights into chronic lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and asthma. Recent papers have reported the possible role of microbiome composition in IPF [13,14]. Increased bacterial burden and presence of specific bacteria have been associated with disease progression.…”