Discussion
Recent studies have led to the implication of viral or bacterial infections in both the initiation and progression of IPF.[5,11,13,16–19] Previously, viral infection was hypothesized to play a predominant role in the initiation and the progression of IPF.[20] However, more recently a role for bacterial infection has also been implicated in the development of rapidly progressive IPF.[11,13,18] Optimal antiviral and antibacterial immunity are vital in the maintenance of lung homeostasis and health in IPF patients.
In this study, we investigated for the first time, the effect of bacterial, viral and co-infection in disease progression in IPF. Here, we demonstrate that IPF patients who are co-infected with bacterial and viral infection has significantly worsened FVC and DLCO function, a greater AE-IPF and reduced survival compared with uninfected patients. Longitudinal rate of decline in FVC (% predicted) is a well-established marker of disease progression and known predictor of mortality in IPF.[21,22] In this study, these effects were associated with a significantly greater risk of mortality (Hazards Ratio: 8.12; 95% CI 1.3–26.9; p= 0.031) using Kaplan Meier survival curve analysis over a period of 60 months follow-up. These results suggest that the status of co-infection in IPF patients may be a good prognostic factor for accelerated disease progression. Additionally, these results suggest that the use of antiviral and/or antibacterial therapies may be useful in treating disease progression in co-infected IPF patients. Currently, clinical trials are underway to investigate the efficacy of the macrolide-type antibiotic, Azithromycin (AZT; ClinicalTrials.gov Identifier: NCT02173145). The antiviral, Valganciclovir, is currently being investigated as an adjuvant therapy with Pirfenidone, in the AE-IPF in patients with a history of CMV infection (ClinicalTrials.gov Identifier: NCT02871401).
