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Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?

Dushianthan, Ahilanandan, Cusack, Rebecca, Goss, Victoria, Postle, Anthony D and Grocott, Mike P.W. (2012) Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here? Critical Care, 16, (6), p. 238. (doi:10.1186/cc11512). (PMID:23171712).

Record type: Article


Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies. Surfactant dysfunction with quantitative and qualitative abnormalities of both phospholipids and proteins are characteristic of patients with ARDS. Exogenous surfactant replacement in animal models of ARDS and neonatal respiratory distress syndrome shows consistent improvements in gas exchange and survival. However, whilst some adult studies have shown improved oxygenation, no survival benefit has been demonstrated to date. This lack of clinical efficacy may be related to disease heterogeneity (where treatment responders may be obscured by nonresponders), limited understanding of surfactant biology in patients or an absence of therapeutic effect in this population. Crucially, the mechanism of lung injury in neonates is different from that in ARDS: surfactant inhibition by plasma constituents is a typical feature of ARDS, whereas the primary pathology in neonates is the deficiency of surfactant material due to reduced synthesis. Absence of phenotypic characterisation of patients, the lack of an ideal natural surfactant material with adequate surfactant proteins, coupled with uncertainty about optimal timing, dosing and delivery method are some of the limitations of published surfactant replacement clinical trials. Recent advances in stable isotope labelling of surfactant phospholipids coupled with analytical methods using electrospray ionisation mass spectrometry enable highly specific molecular assessment of phospholipid subclasses and synthetic rates that can be utilised for phenotypic characterisation and individualisation of exogenous surfactant replacement therapy. Exploring the clinical benefit of such an approach should be a priority for future ARDS research.

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e-pub ahead of print date: 22 November 2012
Published date: 22 November 2012
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 346139
ISSN: 1364-8535
PURE UUID: 004a81ff-f271-4845-b868-697249c4e8c2
ORCID for Anthony D Postle: ORCID iD

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Date deposited: 14 Jan 2013 14:03
Last modified: 18 Jul 2017 05:05

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

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