Stable isotope labelling of phosphatidylcholine synthesis in vivo in children with acute lung injury

Background Acute lung injury (ALI) is an inflammatory lung condition with significant morbidity and mortality, associated with surfactant dysfunction. Surfactant is a lipid–protein mixture composed of 80% phospholipid of which 35–55% is dipalmitoylphosphatidylcholine. The lipid profile of surfactant is significantly altered in patients with ALI,1 but it is not clear whether this is due to decreased surfactant synthesis or increased degradation. Material and Methods This study employs a novel method to quantify surfactant kinetics in children in vivo. Five children, aged 2 months to 3 years, admitted to the paediatric intensive care unit with a clinical diagnosis of ALI, were infused with methyl-D 9 choline chloride. Synthesis of phosphatidylcholine (PC) in sequential lung bronchoalveolar lavage (BAL) and serum samples were analysed by electrospray ionisation tandem mass spectrometry. Results Measurable incorporation of methyl-D 9 choline chloride into both surfactant and serum PC was demonstrated, with peak incorporations of 0.7±0.08% in BAL fluid (BALF) (figure 1) and 3.0±0.8% in serum (figure 2). The rate of surfactant synthesis varied widely and did not correlate with respective measurement of serum PC synthesis, highlighting lung and systemic effects of ALI. Conclusion This study demonstrates the feasibility of methyl-D 9 choline chloride labelling to quantify kinetics of surfactant and serum PC synthesis in children with ALI in vivo. The variation in BALF PC synthesis indicates a wide range of surfactant synthesis/secretion, while comparison with serum PC synthesis suggests that much of this variation is lung specific.