Patients with ARDS show improvement but not normalisation of alveolar surface activity with surfactant treatment: putative role of neutral lipids.
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.


CONCLUSIONS
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.
Markart
Philipp
P
Department of Internal Medicine, Faculty of Medicine, University of Giessen Lung Center, Klinikstrasse 36, 35392 Giessen, Germany.
Ruppert
Clemens
C
Wygrecka
Malgorzata
M
Colaris
Thorsten
T
Dahal
Bhola
B
Walmrath
Dieter
D
Harbach
Heinz
H
Wilhelm
Jochen
J
Seeger
Werner
W
Schmidt
Reinhold
R
Guenther
Andreas
A
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006801:Humans; D008055:Lipids / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000032:analysis; D011650:Pulmonary Alveoli / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000502:physiology; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D005227:Fatty Acids; D008055:Lipids; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C521929:Venticute