title: Viral infection in acute exacerbation of idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation.
  
  
  OBJECTIVE
  To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis.
  
  
  METHODS
  Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing.
  
  
  RESULTS
  Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses.
  
  
  CONCLUSIONS
  Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.
authors.affiliation: UC San Francisco/UC Berkeley Joint Graduate Group in Bioengineering, University of California, Berkeley, California, USA.
authors.forename: Sharon Chao
authors.initials: SC
authors.lastname: Wootton
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Kim
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kondoh
authors.forename: Eunice
authors.initials: E
authors.lastname: Chen
authors.forename: Joyce S
authors.initials: JS
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Song
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Huh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Charles
authors.initials: C
authors.lastname: Chiu
authors.forename: Homer
authors.initials: H
authors.lastname: Boushey
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Lancaster
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wolters
authors.forename: Joseph
authors.initials: J
authors.lastname: DeRisi
authors.forename: Don
authors.initials: D
authors.lastname: Ganem
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
mesh_terms: D000208:Acute Disease; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D004266:DNA Virus Infections / Q000150:complications; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D008297:Male; D046228:Microarray Analysis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000150:complications; D017422:Sequence Analysis, DNA; D022783:Torque teno virus; D014777:Virus Diseases / Q000150:complications*