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A prospective pilot study of the effect of neutrophil elastase on the pulmonary vascular permeability in patients with pneumonia


Some cases of pneumonia may lead to hypoxemia with acute respiratory failure, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which may require intensive management. Neutrophil elastase is thought to be one of the causes of ALI/ARDS, because it raises the pulmonary capillary permeability, lyses of pulmonary connective tissue proteins, and produces leukocyte chemotactic factors. However, a causal relationship between the plasma neutrophil elastase level and changes in the pulmonary capillary permeability has not been established in patients with pneumonia, one of the most serious diseases underlying ALI/ARDS. Therefore, the objective of this study was to determine whether an increase in plasma neutrophil elastase is related to elevation of the pulmonary capillary permeability in patients with pneumonia.


Patients with pneumonia who were hospitalized from November 2008 to April 2009 and had PaO2 ≤60 in room air with no need for mechanical ventilation were prospectively enrolled in the study. Plasma neutrophil elastase levels were collected via blood samples at baseline; 1, 3, and 7 days after the start of the study. Of those enrolled, patients with PaO2/FiO2 ≤150 also had their extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) monitored using the PiCCO system (Pulsion, Munich, Germany) when required by their attending physician. Statistical analysis was performed using the Spearman correlation coefficient (Rs) with P ≤ 0.05 assumed to be significant.


Fourteen patients were enrolled in the study. In six of these patients, the EVLWi and PVPI were measured simultaneously. At baseline, the elastase level and the PVPI showed a strong and significant correlation (Rs = 1.000, n = 6, P < 0.05). All of the plot data of the six patients showed strong correlations of the elastase level with the EVLWi (Rs = 0.750, n = 25, P < 0.01) and the PVPI (Rs = 0.811, n = 25, P < 0.01).


The plasma neutrophil elastase level and the PVPI measured by PiCCO were strongly correlated in patients with pneumonia. This suggests that a rise in the blood level of elastase may elevate the PVPI, resulting in an increased EVLWi. (UMIN Clinical Trials Registry: ID UMIN000002803.)

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Tagami, T., Tosa, R., Hirama, H. et al. A prospective pilot study of the effect of neutrophil elastase on the pulmonary vascular permeability in patients with pneumonia. Crit Care 14 (Suppl 1), P179 (2010).

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