The University of Southampton
University of Southampton Institutional Repository

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

Clinical review: exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?
Clinical review: exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here?
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.
1364-8535
238
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Goss, Victoria
ef02be5d-9318-4f7d-b076-3153555980d0
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Grocott, Mike P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Goss, Victoria
ef02be5d-9318-4f7d-b076-3153555980d0
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Grocott, Mike P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2

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), 238. (doi:10.1186/cc11512). (PMID:23171712)

Record type: Article

Abstract

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.

Text
cc11512 - Version of Record
Available under License Creative Commons Attribution.
Download (642kB)

More information

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

Identifiers

Local EPrints ID: 346139
URI: http://eprints.soton.ac.uk/id/eprint/346139
ISSN: 1364-8535
PURE UUID: 004a81ff-f271-4845-b868-697249c4e8c2
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for Rebecca Cusack: ORCID iD orcid.org/0000-0003-2863-2870
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756
ORCID for Mike P.W. Grocott: ORCID iD orcid.org/0000-0002-9484-7581

Catalogue record

Date deposited: 14 Jan 2013 14:03
Last modified: 23 Apr 2024 01:55

Export record

Altmetrics

Contributors

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

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.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

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.

×