The University of Southampton
University of Southampton Institutional Repository

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

Dushianthan, Ahilanandan, Goss, Victoria, Cusack, Rebecca, Grocott, Michael P.W. and Postle, Anthony D. (2014) Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome Respiratory Research, 15, (1), pp. 1-11. (doi:10.1186/s12931-014-0128-8). (PMID:25378080).

Record type: Article


BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and characterisation of ARDS patients according to patterns of surfactant synthesis and metabolism.MethodsTen patients with moderate to severe ARDS were recruited. Most (90%) suffered from pneumonia. They had an infusion of methyl-D9-choline chloride and small volume bronchoalveolar lavage fluid (BALF) was obtained at 0,6,12,24,48,72 and 96 hours. Controls were healthy volunteers, who had BALF at 24 and 48 hours after methyl-D9-choline infusion. Compositional analysis and enrichment patterns of stable isotope labelling of surfactant phosphatidylcholine (PC) was determined by electrospray ionisation mass spectrometry.ResultsBALF of patients with ARDS consisted of diminished total PC and fractional PC16:0/16:0 concentrations compared to healthy controls. Compositional analysis revealed, reductions in fractional compositions of saturated PC species with elevated levels of longer acyl chain unsaturated PC species. Molecular specificity of newly synthesised PC fraction showed time course variation, with lower PC16:0/16:0 composition at earlier time points, but achieved near equilibrium with endogenous composition at 48 hours after methyl-D9-choline infusion. The enrichment of methyl-D9-choline into surfactant total PC is nearly doubled in patients, with considerable variation between individuals.ConclusionsThis study demonstrate significant alterations in composition and kinetics of surfactant PC extracted from ARDS patients. This novel approach may facilitate biochemical phenotyping of ARDS patients according to surfactant synthesis and metabolism, enabling individualised treatment approaches for the management of ARDS patients in the future.

PDF s12931-014-0128-8.pdf - Version of Record
Available under License Other.
Download (1MB)

More information

Published date: 7 November 2014
Keywords: acute respiratory distress syndrome, acute lung injury, surfactant, phosphatidylcholine, deuterated choline, stable isotopes, isotope labelling, mass spectrometry


Local EPrints ID: 372853
ISSN: 1465-9921
PURE UUID: 737de41f-1760-4e08-8b39-ffb32a66ee25
ORCID for Anthony D. Postle: ORCID iD

Catalogue record

Date deposited: 23 Dec 2014 14:39
Last modified: 17 Jul 2017 21:38

Export record



Author: Ahilanandan Dushianthan
Author: Victoria Goss
Author: Rebecca Cusack

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.