Microarray-based analysis of ventilator-induced lung injury

Abstract

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are a frequent cause of intensive care unit admission, affecting over 200,000 patients in the United States each year. Mechanical ventilation is a life-saving intervention in the setting of ARDS and ALI, but clinical trials have demonstrated that mechanical ventilation with excessive tidal volumes plays a role in promoting and perpetuating lung injury and leads to excess mortality. This process has been labeled ventilator-induced lung injury (VILI), but the molecular mechanisms driving this process and its interactions with predisposing risk factors such as sepsis and chemical injury remain incompletely understood. Genome-wide measurements of gene expression using microarray technology represent a powerful tool to examine the pathophysiology of VILI. Several recent studies have used this approach to study VILI in isolation and associated with endotoxin instillation or saline lavage. These studies and others examining gene expression profiles in epithelial cells subjected to cyclic stretch have provided novel insights on the molecular mechanisms underlying VILI. This review will summarize these findings and discuss implications for future studies.

Figure 1.

Summary of differentially regulated genes. Genes grouped based on differential regulation in the same direction: upper panel, up-regulated; lower panel, down-regulated. ¹Genes differentially regulated across murine, rat, canine, and human models of VILI (p < 0.05; black boxes) (25). ²Genes differentially regulated (95% confidence interval for fold-change not containing 1.0) in murine model of mechanical ventilation alone (black boxes) or mechanical ventilation plus intratracheal lipopolysaccharide (grey boxes) (26). ³Genes differentially regulated in rat model of mechanical ventilation (fold change ⩾ 2 and D ⩾ 0.8) (24). ⁴Genes differentially regulated in murine isolated perfused lung model of mechanical ventilation (false discovery rate ⩽ 0.1; black boxes), or fold change over control ⩾ 2.0 (grey boxes) (27).