http://repub.eur.nl/res/aut/7176/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/13310/ 2004-01-01T00:00:00Z Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on bacterial growth and translocation in a piglet model of Group B streptococcal pneumonia. After creating surfactant deficiency by whole lung lavage, intratracheal instillation of bacteria induced severe pneumonia with bacterial translocation into the blood stream, resulting in a mortality rate of almost 80%. Treatment with 300 mg/kg of exogenous surfactant before instillation of streptococci attenuated both bacterial growth and translocation and prevented clinical deterioration. This goal was also achieved by reversing atelectasis in lavaged animals via open lung ventilation. Combining both exogenous surfactant and open lung ventilation prevented bacterial translocation completely, comparable to Group B streptococci instillation into healthy animals. We conclude that exogenous surfactant and open lung ventilation attenuate bacterial growth and translocation in experimental pneumonia and that this attenuation is at least in part mediated by a reduction in atelectasis. These findings suggest that minimizing alveolar collapse by exogenous surfactant and open lung ventilation may reduce the risk of pneumonia and subsequent sepsis in ventilated patients. http://repub.eur.nl/res/pub/10137/ 2003-01-01T00:00:00Z Pulmonary fibrosis results from excessive fibroblast proliferation and increased collagen deposition and occurs in chronic lung disease of prematurity (CLD). Platelet-derived growth factor (PDGF)-BB is mitogenic for fibroblasts and levels are increased in fibrotic lung disorders. Systemic dexamethasone (DEX) treatment improves pulmonary function and reduces inflammation in infants with or at risk of CLD. However, the effect of DEX treatment on fibroblast activity, PDGF-BB and collagen synthesis in the lungs of CLD patients is uncertain. Bronchoalveolar lavage (BAL) fluids, obtained from 15 infants at risk of CLD before and after DEX treatment, were analysed for fibroblast mitogenicity, PDGF-BB, N-terminal propeptide of collagen type III (PIIINP) and interleukin (IL)-1beta levels and inflammatory cell numbers. After DEX treatment, the mitogenic activity of BAL fluid for fibroblasts was not reduced but increased. The change in mitogenicity correlated with a change in BAL fluid PDGF-BB levels. Furthermore, BAL fluid-induced fibroblast proliferation was blocked using an inhibitor of the PDGF receptor. DEX treatment did not influence PIIINP levels, but reduced IL-1beta levels and inflammatory cell numbers in BAL fluid. This study suggests that dexamethasone treatment does not reduce fibroblast proliferation despite apparent downregulation of inflammation. The present findings do not support the use of dexamethasone for prevention of the fibrotic response in infants at risk of chronic lung disease of prematurity.