Pulmonary complement activation in ventilator induced lung injury and ARDS

This thesis describes a series of preclinical and clinical studies into activation of the complement system in the lungs in the context of ventilator-induced lung injury (VILI) and the acute respiratory distress syndrome (ARDS). In two projects using models of VILI and ARDS the effect of complement inhibition was explored. The overarching hypotheses were that pulmonary complement activation is associated with VILI and ARDS, and that administration of a complement inhibitor would reduce pulmonary complement activation, lung inflammation and lung injury.
Combining the results of the studies in this thesis, we conclude that pulmonary complement is activated in ARDS and pneumonia, though to a similar level in invasively ventilated patients not having ARDS or pneumonia. We also conclude that injurious ventilator settings in animal models can induce complement activation in the lung. However, this phenomenon is not observed in critically ill patients. Finally, the studies of inhibiting complement with C1-INH are neutral, i.e. complement inhibition have no effects in the models used in the preclinical studies.