Permeability: theory vs. practice in lung research

Abstract

An increase in permeability of the pulmonary endothelium or epithelium to proteins and other macromolecules is an important part of many types of lung injury. Assessment of lung alveolar-capillary membrane integrity has been the focus of many investigations, but no single method is best for all conditions. Methods using in vitro preparations, such as cell monolayers, provide the most accurate estimates of biophysical parameters defined from membrane theory, but these models may not accurately represent the in vivo condition. Methods using in vivo preparations, such as indicator dilution techniques and the sheep lung-lymph preparation, are more accurate representations of the clinical condition, but considerable assumptions must be made to estimate the parameters of permeability. The most productive studies of lung permeability make use of at least two methods carefully selected according to their strengths and weaknesses. The challenge is to select the right tools for the job and to interpret the results in light of the weaknesses of the methods used. This will lead to a better understanding of the role of altered permeability in the pathophysiology of lung injury.