Developmental physiology of human surfactant phosphatidylcholine – Intrauterine changes relative to prenatal glucocorticoids (PNG), respiratory distress (RDS) and bronchopulmonary dysplasia (BPD)

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Aims: Surfactant is a complex comprising phosphatidylcholine (PC), phosphatidylglycerol and specific proteins in variable concentrations. Dipalmitoyl-PC (DPPC), palmitoyl-myristoyl-PC (PMPC) and palmitoyl-palmitoleoyl-PC (PPPC) are enriched during surfactant assembly, while other PCs are mainly retained in cells. Particularly, PMPC may be immunologically important (1). While the PC changes of human surfactant differ with gestational age (GA) (2,3), GA effects have never been distinguished from other factors. Objective: To differentiate effects of GA and PNG on surfactant PC profiles at birth associated with RDS and BPD. Methods: From 341 nasopharyngeal suctions at delivery (24.3–42w GA, mean 37.4w; 175 <38w; ANG: 55, RDS: 37, BPD: 9) surfactant was isolated and analysed with tandem mass spectrometry for PC composition. Data were correlated with GA and clinical data. Results: In neonates with no RDS or BPD, DPPC increased until 34w. Thereafter PMPC and PPPC increased at the expense of DPPC until 42w (p<0.001). PNG did not alter the PC profile. In RDS patients the PC profile was different from controls, also in age-matched subgroups (29.7–34; 34.1–39.3w GA): DPPC was decreased (50±4 vs. 46±9% and 52±4 vs. 45±6%, resp.; p<0.001), while arachidonic acid containing PC was increased from 6±2 to 9±3% (p<0.001). RDS patients developing BPD had a decreased fraction of DPPC (37±4 vs. 45±2%; p<0.001). Conclusion: The profile changes of human surfactant PC follow a physiological pattern, with specific increases in PMPC and PPPC from 34–42w GA. The PC profile was altered in RDS compared to age matched controls. In RDS patients developing BPD DPPC was further decreased. Literatur: 1: Gille C, Spring B, Bernhard W, Gebhard C, Basile D, Lauber K, Poets CF. 2007. Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages. J. Lipid Res. 48: 307 - 317 2: Bernhard W, Hoffmann S, Dombrowsky H,. Rau GA, Bertling A, Kappler M, Haitsma J, Freihorst J, von der Hardt H, Poets CF. 2001. Phosphatidylcholine molecular species in lung surfactant - Composition in relation to respiratory rate and lung development. Am. J. Respir. Cell Mol. Biol. 25, 725–731 3: Bernhard W, Schmiedl A, Koster G, Orgeig S; Acevedo C, Poets CF, Postle AD. 2007. Developmental changes in rat surfactant lipidomics in the context of species variability. Ped. Pulmonol. 42, 794-804.

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