Patients with ARDS show improvement but not normalisation of alveolar surface activity with surfactant treatment: putative role of neutral lipids
- Philipp Markart1,
- Clemens Ruppert1,
- Malgorzata Wygrecka2,
- Thorsten Colaris3,
- Bhola Dahal1,
- Dieter Walmrath1,
- Heinz Harbach3,
- Jochen Wilhelm1,
- Werner Seeger1,
- Reinhold Schmidt1,
- Andreas Guenther1
- 1Departments of Internal Medicine, Intensive Care Medicine and Pain Therapy, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany
- 2Departments of Biochemistry, Intensive Care Medicine and Pain Therapy, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany
- 3Departments of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany
- Correspondence to:
Dr A Guenther
Department of Internal Medicine, Faculty of Medicine, University of Giessen Lung Center, Klinikstrasse 36, 35392 Giessen, Germany;
- Received 23 March 2006
- Accepted 1 January 2007
- Published Online First 7 February 2007
Background: Extensive biochemical and biophysical changes of the pulmonary surfactant system occur in the acute respiratory distress syndrome (ARDS).
Methods: The effect of intrabronchial administration of a recombinant surfactant protein C-based surfactant preparation (Venticute) on gas exchange, surfactant composition and function was investigated in 31 patients with ARDS in a randomised controlled phase I/II clinical pilot trial. Bronchoalveolar lavage fluids for surfactant analysis were obtained 3 h before and 48 and 120 h after the first surfactant application. Potentially deleterious effects of surfactant neutral lipids in patients with ARDS were also identified.
Results: Before treatment all patients had marked abnormalities in the surfactant phospholipid and protein composition. In response to surfactant treatment, gas exchange improved and surfactant phospholipid and protein content were almost normalised. Alveolar surface activity was dramatically impaired before treatment and only partially improved after surfactant administration. Further analysis of the bronchoalveolar lavage fluids revealed a twofold increase in neutral lipid content and altered neutral lipid profile in patients with ARDS compared with 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 a 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.
- ARDS, acute respiratory distress syndrome
- BAL, bronchoalveolar lavage
- Fio2, fractional inspired oxygen
- γads, surface tension after 12 s of film adsorption
- γmin, surface tension values after 5 min of film oscillation at minimum bubble radius
- HPTLC, high-performance thin-layer chromatography
- LA, large surfactant aggregate
- Pao2, arterial oxygen tension
- SP, surfactant protein
Published Online First 7 February 2007
This study was supported by Deutsche Forschungsgemeinschaft (DFG), SFB 547, SCHM 1524/2-1, ALTANA Pharma AG, Konstanz, Germany.
Competing interests: WS receives grant and contract support and fees for consulting services by the following companies: Schering AG, Pfizer Ltd, Altana Pharma AG, Lung Rx, Myogen. None of the other authors has any financial relationship with a commercial entity that has an interest in the subject matter or materials discussed in the manuscript.
The study was approved by local institutional review boards/ethics committees at each participating institution and informed consent was obtained from all patients or their legal representatives.