Mechanisms and consequences of lung epithelial injury in severe RSV disease

The studies in this thesis have examined mechanisms and consequences of lung epithelial injury in severe RSV disease. In this context, they specifically contribute to the knowledge of apoptosis and the formation of pulmonary edema. The results of our studies underscore the complexity of the mechanisms underlying epithelial dysfunction and injury during severe RSV disease.
The following conclusions can be drawn from this thesis:
- Activation of the inflammatory response of the lungs to pneumonia virus of mice and mechanical ventilation is mediated by the Fas/FasL system (chapter 3)
- PVM-induced epithelial injury is partly mediated by the Fas/FasL system (chapter 3)
- The effect of the Fas/FasL system on inflammation in response to PVM and MV is not associated with a better outcome in fas-deficient mice with more advanced PVM disease (chapter 3)
- The caspase inhibitor zVAD increases lung inflammation in pneumovirus infection in mice without affecting total lung caspase activity (chapter 4)
- The majority of children with severe RSV disease that are admitted to the PICU for mechanical ventilation fulfill the criteria for ARDS (chapter 5)
- FiO2 is an independent predictor for outcome (duration of mechanical ventilation (MV) and the length of stay (LOS)) in children with RSV-induced ARDS, whereas the PaO2/FiO2-ratio is not (chapter 5)
- Intratracheal instillation of TIP does not affect pulmonary edema formation or clinical outcome in PVM-infected mice (chapter 6)