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The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis

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Title: The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis
Authors: Molyneaux, PL
Cox, MJ
Willis-Owen, SAG
Mallia, P
Russell, KE
Russel, A-M
Murphy, E
Johnston, SL
Schwarte, DA
Wells, AU
Cookson, WOC
Maher, TM
Moffatt, MF
Item Type: Journal Article
Abstract: Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung 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 subjectswithmoderate 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 susceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality reads from all subjects.WeidentifiedHaemophilus, 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.
Issue Date: 15-Oct-2014
Date of Acceptance: 3-Sep-2014
URI: http://hdl.handle.net/10044/1/26521
DOI: 10.1164/rccm.201403-0541OC
ISSN: 1535-4970
Publisher: American Thoracic Society
Start Page: 906
End Page: 913
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 190
Issue: 8
Copyright Statement: © ERS 2013
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Wellcome Trust
Asthma UK
Asthma UK
Funder's Grant Number: 097117/Z/11/Z
G0600879
G1000758
G1000758
096964/Z/11/Z
CH11SJ
CH11SJ
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
idiopathic pulmonary fibrosis
Muc5b
bacteria
microbiome
MUC5B PROMOTER POLYMORPHISM
MICROBIOME
SUSCEPTIBILITY
EXACERBATION
ASSOCIATION
DIVERSITY
SURVIVAL
TOOL
Muc5b
bacteria
idiopathic pulmonary fibrosis
microbiome
Aged
Bacteria
Bacterial Load
Bronchoalveolar Lavage
Bronchoalveolar Lavage Fluid
Bronchoscopy
Case-Control Studies
DNA, Bacterial
Disease Progression
Female
Genetic Markers
Genotyping Techniques
Humans
Idiopathic Pulmonary Fibrosis
Logistic Models
Male
Microbiota
Middle Aged
Mucin-5B
Polymerase Chain Reaction
Polymorphism, Genetic
Prospective Studies
Sequence Analysis, DNA
Bronchoalveolar Lavage Fluid
Humans
Bacteria
Disease Progression
DNA, Bacterial
Genetic Markers
Bronchoscopy
Logistic Models
Case-Control Studies
Prospective Studies
Polymerase Chain Reaction
Sequence Analysis, DNA
Bronchoalveolar Lavage
Polymorphism, Genetic
Aged
Middle Aged
Female
Male
Idiopathic Pulmonary Fibrosis
Mucin-5B
Bacterial Load
Genotyping Techniques
Microbiota
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
idiopathic pulmonary fibrosis
Muc5b
bacteria
microbiome
MUC5B PROMOTER POLYMORPHISM
GENOME-WIDE ASSOCIATION
DISEASE
MICROBIOME
SUSCEPTIBILITY
EXACERBATION
DIVERSITY
SURVIVAL
TOOL
11 Medical and Health Sciences
Respiratory System
Publication Status: Published
Online Publication Date: 2014-09-03
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine