Acute Respiratory Distress Syndrome Clinical Trial
To investigate the epidemiology of adult respiratory distress syndrome (ARDS) and the evolution of the inflammatory process in patients with acute lung injury.
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.
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