Surfactant inhibition in acute respiratory failure : consequences for exogenous surfactant therapy

The neonatal respiratory distress syndrome (RDS) is characterized by immaturity of the lung, resulting in relative or absolute absence of pulmonary surfactant. Worldwide, neonates suffering from RDS have been treated successfully with exogenous surfactant preparations. Currently, exogenous surfactant administration has been accepted as a valuable treatment for this syndrome. Nevertheless, many questions on exogenous surfactant treatment remain unanswered. It has been observed that some infants did not respond to, or had only transient improvement after, a single dose of exogenous surfactant. In other studies it was observed that better clinical outcome was seen in infants treated with either a higher dose of surfactant, or after repeated surfactant substitution. It was argued that exogenous surfactant, after intratracheal substitution, was gradually inhibited by surfactant inhibitors present in the terminal lung units. By giving more exogenous surfactant this inhibition was abolished, resulting in improved lung function. The adult respiratory distress syndrome (ARDS) is characterized by acute respiratory failure (ARF), and high-permeability edema fluid accumulating in the alveolar spaces. From experimental and clinical studies it is known that the pulmonary surfactant system is also disturbed in this syndrome. Recently, a few patients suffering from ARDS have been treated with exogenous surfactant. Although these case reports are poorly documented, the best results were observed in patients treated with high doses of exogenous surfactant. The work presented in this thesis focuses on the mechanisms of inhibition of surfactant function in different animal models of acute respiratory failure. To overcome this inhibition, different treatment modalities with an exogenous surfactant preparation will be presented.

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