Pulmonary MMP-9 activity in mechanically ventilated children with RSV disease

Abstract

RSV infection is a potent stimulus for airway epithelial expression of MMP-9, and MMP-9 activity in vivo is a predictor of disease severity in children with RSV-induced respiratory failure (RSV-RF).

Human airway epithelial cells were infected with RSV A2 strain, and analysed for MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1, a natural inhibitor of MMP-9) release. In addition, endotracheal samples from children with RSV-RF and controls (non-RSV pneumonia and non-lung disease controls) were analysed for MMP-9, TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) activity.

RSV infection of airway epithelia was sufficient to rapidly induce MMP-9 transcription and protein release. Pulmonary MMP-9 activity peaked at 48 hours in infants with RSV-RF compared to controls. In the RSV group, MMP-9 activity and MMP-9:TIMP-1 ratio imbalance predicted higher oxygen requirement and worse Paediatric Risk of Mortality scores. Highest levels of HNE and MPO were measured in the RSV cohort but unlike MMP-9, these neutrophil markers failed to predict disease severity.

These results support the hypothesis that RSV is a potent stimulus for MMP-9 expression and release from human airway epithelium, and that MMP-9 is an important biomarker of disease severity in mechanically ventilated children with RSV lung infection.