RT Journal Article
SR Electronic
T1 High Bacterial Load Predicts Poor Outcomes in Patients with Idiopathic Pulmonary Fibrosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 003145
DO 10.1101/003145
A1 P L Molyneaux
A1 M J Cox
A1 S A G Willis-Owen
A1 K E Russell
A1 P Mallia
A1 A M Russell
A1 S L Johnston
A1 A U Wells
A1 W O C Cookson
A1 T M Maher
A1 M F Moffatt
YR 2014
UL http://biorxiv.org/content/early/2014/02/28/003145.abstract
AB Background Repetitive alveolar damage and aberrant repair may be important in the development of the fatal condition Idiopathic Pulmonary Fibrosis (IPF). The role played by microorganisms in this cycle is unknown.Methods We consecutively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, non-smokers and subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) as controls. 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 qPCR and pyrosequencing.Results Our 65 IPF patients had 3.9×109 copies of the 16S rRNA gene per ml of BAL, two-fold more than the 1.8×109 copies in 44 sex- and smoking-matched controls (P<0.0001). Baseline BAL bacterial burden predicted Forced Vital Capacity (FVC) decline (P=0.02). Patients in the highest tertile of bacterial burden were at a higher risk of mortality compared to subjects in the lowest tertile (hazard ratio 4.59 (95% CI, 1.05-20); P=0.04).Sequencing yielded 912,883 high quality reads from all subjects. Operational Taxonomic Units (OTUs) representing Haemophilus, Streptococcus, Neisseria and Veillonella were 1.5 to 3.5 fold more abundant in cases than controls (P<0.05). Regression analyses indicated that these specific OTUs as well as bacterial burden associated independently with IPF.Conclusions IPF is characterised by an increased bacterial burden in BAL that predicts decline in lung function and death. Clinical trials of antimicrobial therapy may determine if microbial burden is causal or not in IPF progression.