Plasma elastase levels and the development of the adult respiratory distress syndrome.

Abstract

Inflammatory cells, particularly neutrophil granulocytes, have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). In this study, we investigated whether a relationship exists between neutrophil elastase in the plasma of multiple-trauma patients on initial hospital presentation and the subsequent development of lung injury and ARDS. Sixty-one multiple-trauma patients were enrolled prospectively. Neutrophil elastase was measured by a specific radioimmunoassay, and analysis was performed by nonparametric statistical methods. A highly significantly elevated plasma elastase level was found in patients who progressed to ARDS (median 217 ng/ml, range 127 to 480) (n = 8) compared with those who did not (median 117 ng/ml, range 21.4 to 685) (n = 53) (p = 0.009). Significant correlation was found between initial elastase values and subsequent requirement for mechanical ventilation (p = 0.01), lowest arterial oxygen saturation/oxygen supplementation recorded (p = 0.003), and organ failure score (p = 0.006). This study shows that within minutes of the initiating trauma event, there is evidence of enhanced neutrophil degranulation as manifested by elevated levels of immunoreactive neutrophil elastase in the peripheral blood. The level of this enzyme correlates with the degree of subsequent lung injury and ARDS. These findings reinforce the importance of neutrophils and their secretory products in early ARDS disease pathogenesis.

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“…They are supposed to be early indicators of an activated immune response and tissue damage. 4,5 Tremendous increases of such circulating adhesion molecules were found in patients with severe sepsis. 6 The surgical patient is at risk of experiencing hypovolemia and subsequently tissue malperfusion and organ dysfunction.…”

The mercurial nature of neutrophils: still an enigma in ARDS?

“…An important proteinase released from neutrophil granules is neutrophil elastase, which is also elevated in human ARDS samples (43). The inhibition of neutrophil elastase has been demonstrated to reduce epithelial injury in several animal models, including a rat model of cystic fibrosis, a mouse model of pulmonary fibrosis, LPS-induced lung injury, mechanical ventilation-induced lung injury, and in colonic epithelial cells in vitro (56,60,74,88,170), although mice deficient in neutrophil elastase also have impaired host defense against gramnegative bacteria (14).…”

Transepithelial Migration of Neutrophils

“…The role of elastase in the pathogenesis of neutrophil-mediated inflammatory diseases, including ALI/ARDS and inflammatory bowel disease, is strongly supported in the literature. The BAL fluid (132)(133)(134)(135) and plasma (136) of patients with ALI/ARDS are characterized by high levels of elastase, and these levels correlate with the severity of lung injury (134,136). In animal models, elastase administration causes lung injury (137)(138)(139) and elastase inhibition has a protective effect on lung injury (140)(141)(142)(143)(144), as measured by several variables including permeability of the alveolocapillary membrane.…”