Injury to the Developing Lung: experimental and clinic al aspects

Injury to the developing lung or disturbance of normal lung development may lead to a chronic lung disease, bronchopulmonary dysplasia (BPD), which may have long-term effects. BPD is characterized by an arrest of development of the lung and the pulmonary vascular system and occurs in around 20% of ventilated newborns. In the first part of this thesis, different factors that influence the development of BPD are studied, both in an experimental and a clinical setting. We found that components of the TGF-b/BMP signalling pathway play a central role in normal and abnormal late lung development. In addition, angiogenic factors, inflammatory cytokines and the nitric oxide system are shown to be of influence. Another factor in the aetiology of BPD is intra-uterine growth retardation. The second part of this thesis focuses on surfactant treatment in acute neonatal lung disorders. Surfactant therapy has become the standard therapy for respiratory distress syndrome in premature infants. There is a significant amount of evidence that near-term or term infants, as well as children, with acute respiratory failure have a profound functional surfactant deficiency. In an experimental setting, we compared synthetic versus natural surfactant and we demonstrated for the first time that both types of surfactant have a positive influence on lung function. However, synthetic surfactant had a significantly stronger effect on inflammatory cytokines. Thus, synthetic surfactant may cause less chronic lung disease and it may be an important part of treatment of these infants in the future.

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