In a recent symposium paper including an explanation of the pathophysiology and histopathology of ARDS, the author stated that the early phase of acute lung injury is characterized by leakage of protein-rich edema fluid into the lung.1 This is not the case: a recent study showed that in this phase of ARDS the pulmonary leak index, as calculated by measuring extravasation of gallium-labeled transferrin, was not elevated.2
A key mechanism in early ARDS is reduced pulmonary fluid clearance, which is a predictor of mortality3 and caused by a reduction in respiratory epithelial sodium and chloride transport removing water from the alveolar space through osmosis.4 Transient ion channel dysfunction caused by inflammatory mediator induced reversible nitrosylation or phosphorylation5 explains the rapid reversibility of pulmonary edema in a majority of patients with sepsis induced pulmonary edema. This rapid reversibility is against structural damage to the alveolar endothelial barrier. Elevated sweat sodium and chloride levels, which reflect impairment of systemic epithelial ion transport, were found to be associated with sepsis related pulmonary edema and its severity, as expressed by ventilation index and duration of mechanical ventilation,4 and should be evaluated as a prognostic marker and risk factor for ARDS.
- Copyright © 2012 by Daedalus Enterprises Inc.
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The author replies:
I thank Michael Eisenhut for his interest and comments about a recent symposium paper published in the Journal.1 While I could not argue against a reduced pulmonary fluid clearance in the early phases of ARDS, disturbances in the endothelial and epithelial sides of the alveolar barrier, manifested by deterioration of the pulmonary function, usually represent the sum total effect of numerous cellular and molecular processes. The importance of endothelial injury to the formation of pulmonary edema in this disorder has been well established.2 Simultaneous and/or sequential activation of signaling pathways, caused by different insults and stimuli in the pulmonary endothelium, interstitium, and epithelium, result in increased permeability to plasma solutes and water with flooding of the interstitial and alveolar space.
Since in some patients, pulmonary edema can resolve quickly, it is likely that those patients do not have the same characteristic pathological abnormalities as those who have diffuse alveolar damage, as could be the case in many patients from the series of patients reported by Aman et al.3 As pointed out by Schuster, almost 20 years ago,4 those patients should not be classified as ARDS but as some alternative form of non-cardiogenic pulmonary edema.
To document the permeability disorder in early ARDS, we measured simultaneously the total plasma protein concentration and the protein concentration in the bronchial aspirate of 22 ARDS patients within the first 12 hours of ARDS onset.5 In all patients, the bronchial aspirate/plasma protein ratio was ≥ 0.6 (mean 0.75 ± 0.10, range 0.60-0.98) and there were no significant differences between the mean values in survivors (0.78 ± 0.13, n = 8) versus non-survivors (0.73 ± 0.09, n = 14). In all cases, pulmonary capillary wedge pressure was lower than 14 mm Hg during the study period (mean 9 ± 2 mm Hg). When the relationship between pulmonary capillary wedge pressure and the bronchial aspirate/plasma protein ratio was evaluated, a statistically significant inverse correlation between both parameters were found (P = .025).
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