BACKGROUND:

The results provided: a) a better understanding of the evolution of inflammation in clinical conditions leading to lung injury; b) a better understanding of the mechanisms of the initial injury and its propagation; and c) information that will help predict the course and outcome in individual patients. These data should be useful in guiding the choice and timing of specific therapeutic interventions.

DESIGN NARRATIVE:

The study was a subproject within a Specialized Center of Research (SCOR) in Acute Lung Injury. Leonard Hudson was the subproject principal investigator. The epidemiological aspects focussed on refining clinical criteria that predicted patients at high risk for the onset of ARDS, and identifying these patients as early as possible before the onset of lung injury. The major hypothesis was that uncontrolled and sustained alveolar inflammation increased the severity of ARDS and prolonged its course, and that sustained inflammation was more likely to occur when ARDS followed sepsis syndrome than multiple trauma. The investigators also tested the hypothesis that the pattern of the inflammatory response in blood and lungs was an important determinant of whether lung inflammation persisted or resolved. Important components of the inflammatory response studied included; 1) a coordinated sequence of cytokines in blood and lung lavage fluid; 2) the expression of adhesion molecules on blood leukocytes; 3) circulating markers of diffuse endothelial injury (VWF and ELAM1); 4) products of the arachidonic acid cascade; 5) the induction of endogenous proteins that modified the host response to bacterial products such as endotoxin; and 6) inflammatory cell populations and proteins in the lung. Patterns of inflammation were correlated with clinical risks, critical clinical events, and outcome measures.

The study was renewed in 1999 to : develop clinical prediction tools that provide individual risk assessment for the onset and outcome of lung injury; determine the incidence and outcome of acute lung injury / adult respiratory distress syndrome (ALI/ARDS) in populations beyond a single institution; determine the relationship between inflammatory responses and injury to the lung endothelial and epithelial barriers; and investigate determinants of host susceptibility that modulate the occurrence of ALI/ARDS in patients at risk.