Acid aspiration induced'lung injury was welldescribed in a classic report by Mendelson in 1946. In that report, 66 women had acute respiratory failure resulting from aspiration of stomach contents into the lungs during labor (1). Since that time, several medical and surgical studies have documented the importance of aspiration of gastric contents as a major cause of acute respiratory failure in adult patients. In fact, in some studies, aspiration of gastric contents is either the second or third most frequent cause of the adult respiratory distress syndrome (2, 3). Mortality rates for patients who suffer acute lung injury from aspiration of gastric contents range from 40 to 50%(2-4). Unfortunately, no therapy has been shown to be effective in reducing the severity of lung injury. Thus, current clinical treatment is limited to supportive measures including positive pressure ventilation with positive end-expiratory pressure, judicious use of antibiotics for secondary pulmonary infections, and careful management of fluid therapy to avoid an increase in the degree of pulmonary edema in the injured lung (5, 6). However, recent experimental work from several investigators indicates that new therapeutic options may become available to treat acid aspiration induced lung injury.

The pathogenesis of acid aspiration lung injury is now reasonably wellunderstood. Direct injury from the acid in aspirated gastric contents is probably limited because the acid itself is rapidly neutralized after instillation (7). If the low pH itself does not cause lung injury, what is responsible for the increase in lung endothelial and epithelial permeability to protein with subsequent protein-rich pulmonary edema? Aspiration of acidic contents into the airspaces of the lung induces the release of pro-inflammatory cytokines, such as tumor necrosis factor-a (8) and interleukin-8 (9). These and other cytokines are responsible for recruitment and activation of neutrophils to the injured lung. In several studies, acid induced lung injury has been markedly reduced either by blocking neutrophil activation or by depleting neutrophils (9-11). Once the neutrophils are sequestered in the microcirculation of the lung, they bind to and migrate through the pulmonary capillary endothelium and alveolar epithelium. The major chemotactic stimulus for neutrophil recruitment into the lung appears to be interleukin-8 (9). However, the chemoattraction of large numbers of neutrophils into the air spaces of the lung alone is not sufficient to cause injury to the pulmonary endothelium or alveolar epithelium. In fact, both experimental and clinical studies have demonstrated that neutrophil recruitment alone can occur without any alteration of lung endothelial or epithelial permeability to protein (12, 13). Therefore, activation of neutrophils must be an important step in the process of acid induced lung injury.