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

Ahilanandan Dushianthan,Anthony D Postle,Victoria Goss,Rebecca Cusack,Michael Pw Grocott

doi:10.1186/s12931-014-0128-8

Abstract

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.

Highlights

Surfactant complex is a mixture of phospholipids and proteins
Mass spectrometry analysis of bronchoalveolar lavage fluid (BALF) PC The molecular species of glycerophospholipids such as phosphatidylcholines can be classified according to the nature of esterified bond at the sn-1 and sn-2 positions of glycerol back bone, the number of carbon atoms in the fatty acid chains and the number
This study conducted on a small number of Acute respiratory distress syndrome (ARDS) patients illustrates the feasibility of performing stable isotope labelling in combination with ESI-MS/MS analytical methods to investigate surfactant phospholipid metabolism in a defined human patient cohort

Summary

Introduction

Surfactant complex is a mixture of phospholipids and proteins. Phosphatidylcholine is the major surfactant phospholipid and among the several species, PC16:0/ 16:0 is the principle PC, thought to be actively involved in surface reduction at the air-liquid interface [1]. In patients with respiratory failure secondary to acute respiratory distress syndrome (ARDS), the lavaged surfactant complex show compositional derangement and lacks adequate surface activity [2,3]. These changes are likely to contribute to the detrimental clinical features of severe hypoxemia, poor lung compliance and lung atelectasis, which are characteristic of ARDS. Acute 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. 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

Methods

Results

Discussion

Conclusion