The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Surfactant phospholipid kinetics in patients with Acute Respiratory Distress Syndrome (ARDS)

Surfactant phospholipid kinetics in patients with Acute Respiratory Distress Syndrome (ARDS)
Surfactant phospholipid kinetics in patients with Acute Respiratory Distress Syndrome (ARDS)
Introduction and Aims ARDS is a significant health burden. Mortality still remains high between 30–50%. Surfactant is a mixture of phospholipids and proteins. Phosphatidylcholines (PC) account for 80% of total phospholipids. PC16:0/16:0 is the main PC with surface tension reducing characteristics. Surfactant abnormalities are well recognised in patients with ARDS However, replacement strategies remain unhelpful in improving mortality. Existing diagnostic definitions fail to identify a homogeneous population and this lack of phenotyping of patients according to surfactant biology may in part explain the absence of therapeutic benefit. The aims of this study are to assess surfactant PC kinetics by the incorporation of methyl-D9-choline in patients with ARDS. Methods ARDS patients were identified according to American European Consensus Conference (AECC) criteria. Patients were infused with 3.6mg/kg methyl-D9-choline. Small volume bronchoalveolar lavages were performed via a fibre optic bronchoscope at serial time points. Healthy volunteers were used as controls. The phospholipid fraction was extracted and analysed by triple quadrupole electrospray ionisation mass spectrometry. Results Ten patients and nine healthy controls were recruited. The endogenous PC composition consisted primarily of PC16:0/16:0, PC16:0/18:1 and PC18:0/18:2. There was significant reduction in the relative proportion of endogenous PC16:0/16:0 in patients. Compared to healthy controls, newly synthesised deuteriated PC16:0/16:0 was much lower in patients (26%) than controls (47%). Total surfactant PC D9-incorporation was linear until 48 hours (0.019%/h, r2=0.9734, P<0.05) and reached its maximum at 48 hours (0.93±0.15%). Steady state of incorporation was achieved between 48–96 hours. There was ∼80% increase in the fractional D9 labelling in patients at 48 hours compared to healthy controls. Total plasma PC D9-incorporation was linear until 24 hours (0.032%/h, r2=0.9825, P<0.05) and reached its maximum (0.755±0.056%) at 24 hours. Linear decline in enrichment was noted after 24 hours at a rate of 0.003% per hour (r2=0.9915, P<0.05). The total surfactant PC D9-incorporation was much higher for patients at 24 hours and 48 hours reflecting increased synthetic rate. Conclusions By labelling surfactant PC precursors, it is possible to study surfactant kinetics in patients with ARDS. The methodology may be utilised to phenotype patients according to alveolar surfactant kinetics prior to replacement strategies.
0040-6376
p. A30
Dushianthan, A.
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, R.
dfb1595f-2792-4f76-ac6d-da027cf40146
Goss, V.
ef02be5d-9318-4f7d-b076-3153555980d0
Grocott, M. P. W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Postle, A. D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Dushianthan, A.
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, R.
dfb1595f-2792-4f76-ac6d-da027cf40146
Goss, V.
ef02be5d-9318-4f7d-b076-3153555980d0
Grocott, M. P. W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Postle, A. D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66

Dushianthan, A., Cusack, R., Goss, V., Grocott, M. P. W. and Postle, A. D. (2012) Surfactant phospholipid kinetics in patients with Acute Respiratory Distress Syndrome (ARDS). Thorax, 67, p. A30, [S58]. (doi:10.1136/thoraxjnl-2012-202678.064).

Record type: Meeting abstract

Abstract

Introduction and Aims ARDS is a significant health burden. Mortality still remains high between 30–50%. Surfactant is a mixture of phospholipids and proteins. Phosphatidylcholines (PC) account for 80% of total phospholipids. PC16:0/16:0 is the main PC with surface tension reducing characteristics. Surfactant abnormalities are well recognised in patients with ARDS However, replacement strategies remain unhelpful in improving mortality. Existing diagnostic definitions fail to identify a homogeneous population and this lack of phenotyping of patients according to surfactant biology may in part explain the absence of therapeutic benefit. The aims of this study are to assess surfactant PC kinetics by the incorporation of methyl-D9-choline in patients with ARDS. Methods ARDS patients were identified according to American European Consensus Conference (AECC) criteria. Patients were infused with 3.6mg/kg methyl-D9-choline. Small volume bronchoalveolar lavages were performed via a fibre optic bronchoscope at serial time points. Healthy volunteers were used as controls. The phospholipid fraction was extracted and analysed by triple quadrupole electrospray ionisation mass spectrometry. Results Ten patients and nine healthy controls were recruited. The endogenous PC composition consisted primarily of PC16:0/16:0, PC16:0/18:1 and PC18:0/18:2. There was significant reduction in the relative proportion of endogenous PC16:0/16:0 in patients. Compared to healthy controls, newly synthesised deuteriated PC16:0/16:0 was much lower in patients (26%) than controls (47%). Total surfactant PC D9-incorporation was linear until 48 hours (0.019%/h, r2=0.9734, P<0.05) and reached its maximum at 48 hours (0.93±0.15%). Steady state of incorporation was achieved between 48–96 hours. There was ∼80% increase in the fractional D9 labelling in patients at 48 hours compared to healthy controls. Total plasma PC D9-incorporation was linear until 24 hours (0.032%/h, r2=0.9825, P<0.05) and reached its maximum (0.755±0.056%) at 24 hours. Linear decline in enrichment was noted after 24 hours at a rate of 0.003% per hour (r2=0.9915, P<0.05). The total surfactant PC D9-incorporation was much higher for patients at 24 hours and 48 hours reflecting increased synthetic rate. Conclusions By labelling surfactant PC precursors, it is possible to study surfactant kinetics in patients with ARDS. The methodology may be utilised to phenotype patients according to alveolar surfactant kinetics prior to replacement strategies.

This record has no associated files available for download.

More information

e-pub ahead of print date: 19 November 2012
Published date: December 2012

Identifiers

Local EPrints ID: 437377
URI: http://eprints.soton.ac.uk/id/eprint/437377
ISSN: 0040-6376
PURE UUID: d74eb85f-4133-4bb2-878f-2b68dbce2e2f
ORCID for A. Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for M. P. W. Grocott: ORCID iD orcid.org/0000-0002-9484-7581
ORCID for A. D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

Catalogue record

Date deposited: 29 Jan 2020 17:30
Last modified: 10 Nov 2021 03:53

Export record

Altmetrics

Contributors

Author: A. Dushianthan ORCID iD
Author: R. Cusack
Author: V. Goss
Author: A. D. Postle ORCID iD

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.

×