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Clinical studies into the pathogenesis of acute lung injury
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S40 LIPOPOLYSACCHARIDE INHALATION DRIVES PULMONARY INFLAMMATION AND CAUSES ALVEOLAR EPITHELIAL AND ENDOTHELIAL ACTIVATION/INJURY IN AN IN VIVO HUMAN MODEL OF ACUTE LUNG INJURY

1M. Shyamsundar, 1S. McKeown, 2C. Calfee, 1B. Thompson, 1C. O’Kane, 3D. Thickett, 1T. Craig, 2M. Matthay, 1J. S. Elborn, 1D. McAuley. 1Respiratory Medicine Research Programme, Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University of Belfast, Belfast, UK, 2Cardiovascular Research Institute, University of California, San Francisco, California, USA, 3Lung Injury and Fibrosis Treatment Programme, School of Experimental and Clinical Medicine, University of Birmingham, Birmingham, UK

Acute lung injury (ALI) is an inflammatory process characterised by damage to the alveolar epithelial–capillary endothelial barrier leading to alveolar flooding. The objective of this study was to determine if lipopolysaccharide (LPS) inhalation, as an in vivo human model of ALI, causes alveolar epithelial and endothelial activation/injury.

Ten healthy subjects, enrolled in the placebo arm of a clinical trial,1 who inhaled 50 μg of LPS, and 5 healthy controls were recruited. Bronchoalveolar lavage (BAL) was performed at 6 h and plasma sampling at 24 h after LPS inhalation. Surfactant protein-D (SP-D), an alveolar type 2 epithelial cell biomarker, von Willebrand factor (vWF), an endothelial cell biomarker, and calgranulin C reflecting neutrophil and/or macrophage activation were measured by ELISA. Cytokines were measured by cytometric bead array. The protein permeability index (PPI) (BAL protein/plasma protein ratio) was calculated as a marker of barrier integrity. Data are mean (±SD) or median (interquartile range).

LPS inhalation induced a significant increase in BAL SP-D (fig 1a) and BAL vWF (fig 1b). There was a significant increase in plasma SP-D (ng/ml) (107.3 (69.2–132.2) vs 35.4 (28.8–61.5), p = 0.005) but no change in plasma vWF levels. BAL calgranulin C (pg/ml) was also increased (176.8 (90.1) vs 5.1 (3), p<0.001). There was an associated increase in BAL interleukin-6 (IL-6) (pg/ml) (509.8 (264.0) vs (1.6 (0.5) …

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