Acute respiratory failure due to acute parenchymal lung injury (acute lung injury/acute respiratory distress syndrome or ALI/ARDS) is a common problem in both adult and pediatric critical care and is associated with significant morbidity and mortality. Human and animal data support the role of surfactant dysfunction in the disturbed lung function of ALI/ARDS and a variety of animal models have shown significant improvement with administration of exogenous surfactant. However, not all critically ill patients with ALI/ARDS respond positively to surfactant replacement. For example, post-hoc analyses suggest that patients with direct ALI/ARDS (e.g. ALI/ARDS secondary pneumonia, aspiration, smoke inhalation, etc) respond better to surfactant replacement compared to patients with indirect ALI/ARDS (e.g. ALI/ARDS secondary to sepsis, acute pancreatitis, trauma, etc). In addition, several gene polymorphisms associated with ALI/ARDS have been described which may alter the host response to surfactant administration. Surfactant functions to decrease surface tension during normal tidal breathing and is an integral part of the innate lung defense. The improvement in lung mechanics and oxygenation following surfactant administration has been associated with improved survival in critically ill children with ALI/ARDS, though other factors may play a role as well. For example, surfactant has been shown to directly inhibit pro-inflammatory gene expression in vitro and in vivo. However, clinical studies demonstrating these anti-inflammatory effects in critically ill patients are notably lacking. The goals of the current proposal therefore are to (1) further elucidate the mechanisms by which calfactant administration improves survival and (2) determine what genetic factor(s) are associated with a clinical response to calfactant administration in critically ill children with ALI/ARDS. Acute respiratory failure due to acute parenchymal lung injury (acute lung injury/acute respiratory distress syndrome or ALI/ARDS) is a common problem in both adult and pediatric critical care and is associated with significant morbidity and mortality. While there is evidence to suggest that surfactant administration improves oxygenation in critically ill children with so-called """"""""direct"""""""" ALI/ARDS (e.g. due to pneumonia or smoke inhalation), not all critically ill patients with ALI/ARDS respond positively to surfactant replacement. Our goal is to determine the genetic factors that may alter the response to surfactant in patients with direct lung injury.
