Viral Infection Increases the Risk of Idiopathic Pulmonary Fibrosis: A Meta-analysis.
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with a poor prognosis. Although many factors have been identified to possibly trigger or aggravate IPF, such as viral infection, the exact etiology of IPF remains unclear. Until now, there has been no systematic review to quantitatively assess the role of viral infection in IPF.
Objective: This meta-analysis aims to present a collective view on the relationship between viral infection and IPF.
Methods: We searched studies reporting the effect of viral infection on IPF from Pubmed, Embase, Cochrane Library, Web of Science, and Wiley Online Library databases. The value of OR with 95% CI was calculated to assess the risk of virus in IPF. We also estimated statistical heterogeneity by I2 and Cochran Q test, publication bias by funnel plot, Begg's test, Egger's test and trim and fill method. Regression, sensitivity and subgroup analyses were performed to assess the effects of confounding factors, such as gender and age.
Results: We analyzed 20 case-control studies with 1287 participants from 10 countries. The pooled OR of all viruses indicated that viral infection could significantly increase the risk of IPF (OR: 3.48, 95% CI: 1.61-7.52, p=0.001), but not that of exacerbation of IPF (OR: 0.99, 95% CI: 0.46-2.12, p=0.988). In addition, all analyzed viruses including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 7 (HHV7) and human herpesvirus 8 (HHV8) were associated with a significant elevation in the risk of IPF, except human herpesvirus 6 (HHV6).
Conclusions: The presence of persistent or chronic, but not acute, viral infections including EBV, CMV, HHV7 and HHV8, significantly increases the risk of developing IPF, but not exacerbation of IPF. These findings imply that viral infection could be a potential risk factor for IPF.