Viral Infection in Acute Exacerbation of Idiopathic Pulmonary FibrosisSharon Chao Wootton, Dong Soon Kim, Yasuhiro Kondoh, Eunice Chen, Joyce S Lee, Jin Woo Song, Jin Won Huh, Hiroyuki Taniguchi, Charles Chiu, Homer Boushey, Lisa H Lancaster, Paul J Wolters, Joseph DeRisi, Don Ganem, and Harold R Collard
Am. J. Respir. Crit. Care Med. 2011Abstract: Rationale: 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. Objectives: 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 acute exacerbation of idiopathic pulmonary fibrosis patients 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 acute exacerbation patients. TTV infection was significantly more common in acute exacerbation patients 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 the majority of acute exacerbation of idiopathic pulmonary fibrosis cases. TTV was present in a significant minority of cases, as well as cases of acute lung injury; the clinical significance of this finding remains to be determined.
