Role of pulmonary surfactant in the development and treatment of adult respiratory distress syndrome

Academic Article

Abstract

  • The goal of this article has been to examine the role of pulmonary surfactant system alterations in the development of ARDS, and the potential efficacy of surfactant replacement therapy in ARDS and ARDS-type injuries. Data from patients with ARDS and animal models with ARDS-type injuries clearly indicate the existence of a surfactant-deficient state. However, in contrast to neonatal RDS, this deficiency generally does not represent to primary pathogenic factor. The diversity of the disorders associated with ARDS has made it impossible to develop a single-animal model that can be used to test potential therapeutic measures. The ARDS animal models that have been developed are equally diverse, and represent the wide variations in severity and time-course seen clinically. Nevertheless, almost all of the lung injury models show indications of surfactant abnormality, which is caused mainly by biophysical inhibition of surfactant activity by the large amount of proteinaceous edema found in the injured lungs. In some cases, this surfactant dysfunction is further compounded by a quantitative surfactant deficiency brought about by metabolic alterations of the type II pneumocytes. It is important to note that all of the lung injury models studied thus far have shown sigificant improvements in pulmonary mechanics and arterial oxygenation after treatment with exogenous surfactant. Such results are consistent with biophysical studies that suggest that increasing the effective surfactant concentration in the lung should mitigate the effects of both quantitative and functional surfactant deficiencies. Although animal studies suggest that surfactant replacement therapy might be efficacious in ARDS, there is a good deal of experimental work that still needs to be done. Most of what we know about clinical surfactant therapy has been developed through the treatment of neonatal RDS, and the practical problems of scaling up surfactant delivery for adult applications are significant. It is clear that sustained beneficial effects necessitate multiple instillations of large amounts of exogenous surfactant (between 50 and 300 mg/kg body wt of lipid). There is concern that the distribution of the instilled surfactant will be grossly nonuniform, with injured areas receiving little or no surfactant. Thus, the optimization of the delivery method, dosage, and timing of delivery should first be further considered in the laboratory before considerations of clinical trials. Nevertheless, data presently available from animal studies and a limited number of patients show that in spite of these problems surfactant administration may improve the outcome of patients with ARDS.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Holm BA; Matalon S
  • Start Page

  • 805
  • End Page

  • 818
  • Volume

  • 69
  • Issue

  • 6