Patients with ARDS show incomplete restoration of alveolar surface activity upon recombinant SP-C-based surfactant treatment: putative role of neutral lipids

Philipp Markart ¹, Clemens Ruppert ¹, Malgorzata Wygrecka ², Thorsten Colaris ³, Bhola Dahal ¹, Dieter Walmrath ¹, Heinz Harbach ³, Jochen Wilhelm ¹, Werner Seeger ¹, Reinhold Schmidt ¹ and Andreas Guenther ^1*

¹ Department of Internal Medicine, University of Giessen Lung Center, Germany
² Department of Biochemistry, University of Giessen Lung Center, Germany
³ Department of Anaesthesiology, University of Giessen Lung Center, Germany

^* To whom correspondence should be addressed. E-mail: andreas.guenther{at}innere.med.uni-giessen.de.

Accepted 1 January 2007

Abstract

Background: Extensive biochemical and biophysical changes of the pulmonary surfactant system occur in the acute respiratory distress syndrome (ARDS).

Methods: In the present study, we investigated the effect of intrabronchial administration of a recombinant surfactant protein C-based surfactant preparation (Venticute) on gas exchange, surfactant composition and function of 31 ARDS patients, participating in a randomized, controlled, phase I/II clinical pilot trial. Additionally, we identified the potentially deleterious effects of surfactant neutral lipids in ARDS subjects.

Results: Prior to treatment, all ARDS patients displayed marked abnormalities in the surfactant phospholipid and protein composition and possessed dramatically impaired surface activity. In response to surfactant treatment, gas exchange improved and surfactant phospholipid and protein content were virtually normalized, however, surface activity was only partially improved. Further analysis of the bronchoalveolar lavage fluids revealed a two fold increase in neutral lipid content and altered neutral lipid profile in ARDS patients compared to healthy controls. These differences persisted even after administration of large amounts of Venticute. Supplementation of Venticute or natural surfactant with a synthetic neutral lipid preparation, mimicking the profile in ARDS, caused dose-dependent deterioration of surface activity in vitro.

Conclusion: Intrabronchial surfactant treatment improves gas exchange in ARDS, but the efficacy may be limited by increased concentration and altered neutral lipid profile in surfactant under these conditions.

Keywords: acute lung injury, acute respiratory distress syndrome, cholesterol, lipids, pulmonary surfactant

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