Reply: Defining Lung Injury in Animals

From the Authors:

We thank the editors for giving us the opportunity to reply to the interesting issues raised in the letter by Zarogiannis and Matalon. Before addressing their specific questions, we would like to point out that our article (1) was meant to serve as the basis for a discussion on lung injury that would eventually lead to revised, improved criteria. Thus, we welcome the questions of Zarogiannis and Matalon.

Their first question is highly relevant in that it describes an animal model of Cl₂ exposure in which there is clinical, physiological, and biochemical evidence of lung injury, but with minimal evidence of inflammatory alveolitis. Interestingly, while there was evidence of injury to the airways epithelium on histologic examination, there was also evidence of leak of fluid and plasma proteins into the lung. This raises several important issues. First, injury predominantly to the airway epithelium can lead to flooding of the alveolar compartment with protein-rich edema fluid. This underscores the close interactions between the distal airways and alveolar space and how changes in one compartment can lead to alterations in the other. Second, the rodent model of Cl₂-induced lung injury appears to display relatively little parenchymal inflammation (defined by “pneumonitis” on histology), yet has prominent physiological manifestations, including respiratory distress and severe hypoxemia. This model illustrates the dissociation between the acute inflammatory response and lung injury that has also been reported in other circumstances. Thus, each animal model should be evaluated in terms of its intended purpose and the specific questions that it was intended to address. In this case, the authors have an excellent model of exposure to irritant gases that reproduces the evolution to reactive airways disease.

Regarding their second question, we thank the authors for pointing out the importance of potential changes in the volume of distribution when measuring labeled albumin or Evans blue dye extravasation that might have important effects on the measurements in animal models of lung injury.