Acute Diesel Exhaust Particle Exposure Increases Viral Titre Associated With Influenza But Does Not Exacerbate Inflammation Or Deficits In Baseline Lung Function

Introduction: Diesel exhaust particles (DEP) make up the bulk of particulate matter in urban areas. High ambient levels of particulate matter are associated with increased hospitalisation due to respiratory disease, including respiratory viral infection. We aimed to determine if exposure to DEP exacerbates responses to acute influenza infection using mouse models of these diseases.

Methods: Adult female BALB/c mice were inoculated with 100μg DEP or control 3.75 days after infection with 10 plaque forming units 4.5 (pfu) of influenza A/Mem71 (or control). Six hours after DEP inoculation lung volume (TGV) and lung mechanics were measured by plethysmography and the forced oscillation technique respectively. The volume dependence of lung mechanics was assessed by slowly inflating the lungs to a transrespiratory pressure of 20 cm H O. Bronchoalveolar lavage fluid (BAL) was collected to assess cellular 2 inflammation and cytokine levels. Whole lungs were taken for measurement of viral titre.

Results: Viral titre was significantly higher in influenza infected mice exposed to DEP compared to those exposed to influenza alone (p = 0.04). Both DEP (p = 0.03) and influenza infection (p < 0.001) alone significantly increased cellular inflammation, however there was no difference between mice exposed to both DEP and influenza compared to those exposed to influenza alone (p = 0.42). A similar pattern was found in levels of cytokines in the BAL (TNF-α, MCP-1, IL-6, IFNγ). Specific baseline airway resistance, tissue damping, tissue elastance and hysteresivity were significantly increased in influenza infected mice (p < 0.01 in all cases). None of these parameters was influenced by DEP exposure alone (p > 0.33 in all cases) and there was no additive effect of DEP on baseline lung function in influenza infected mice (p > 0.22 in all cases). Influenza infection and DEP exposure both significantly altered the volume dependence of lung mechanics and there was a significantly increased alteration in airway resistance (p = 0.05) at high lung volumes in infected mice also exposed to DEP, compared to those infected with influenza alone.

Conclusions: An acute exposure to DEP increases peak viral titre but is not sufficient to physiologically exacerbate pre-existing respiratory disease caused by influenza infection in mice when measured at FRC.