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.