The University of Southampton
University of Southampton Institutional Repository

Airway surfactant protein D deficiency in adults with severe asthma

Airway surfactant protein D deficiency in adults with severe asthma
Airway surfactant protein D deficiency in adults with severe asthma
Background: Surfactant protein D (SP-D) is an essential component of the innate immune defence against pathogens within the airways. In addition SP-D regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma.

Methods: SP-D concentrations were measured in matched serum and bronchoalveolar lavage (BAL) samples collected from 10 healthy controls (HC) and 50 asthmatics (22 mild [MA] and 28 severe [SA]). These samples were also evaluated by Western blots to investigate variations in SP-D size.

Results: SP-D levels in BAL were significantly lower in SA compared to HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein (ECP) concentrations in severe asthma (P < .01). Serum SP-D was significantly increased in SA when compared to HC and MA (P < .001), BAL/serum ratios were significantly lower in SA compared to HC and MA (P < .001). Reduced SP-D levels in in BAL with concomitant rises in serum in SA were associated with degraded fragments of SP-D in the serum and increased BAL neutrophils and lipopolysaccharide levels.

Conclusions: These findings suggest defective innate immunity within the airways in severe asthma, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in severe asthmatics may provide a peripheral blood biomarker reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.
0012-3692
1165-1172
Mackay, R-M.
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Grange, C.
cd801c42-3fbe-4170-b2de-b0341f4e2d79
Lau, L.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Barber, C.
ff31b460-34c3-466c-90e4-f70b3e954c82
Clark, H.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Howarth, P.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Mackay, R-M.
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Grange, C.
cd801c42-3fbe-4170-b2de-b0341f4e2d79
Lau, L.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Barber, C.
ff31b460-34c3-466c-90e4-f70b3e954c82
Clark, H.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Howarth, P.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21

Mackay, R-M., Grange, C. and Lau, L. et al. (2016) Airway surfactant protein D deficiency in adults with severe asthma. Chest, 149 (5), 1165-1172. (doi:10.1016/j.chest.2015.11.012).

Record type: Article

Abstract

Background: Surfactant protein D (SP-D) is an essential component of the innate immune defence against pathogens within the airways. In addition SP-D regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma.

Methods: SP-D concentrations were measured in matched serum and bronchoalveolar lavage (BAL) samples collected from 10 healthy controls (HC) and 50 asthmatics (22 mild [MA] and 28 severe [SA]). These samples were also evaluated by Western blots to investigate variations in SP-D size.

Results: SP-D levels in BAL were significantly lower in SA compared to HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein (ECP) concentrations in severe asthma (P < .01). Serum SP-D was significantly increased in SA when compared to HC and MA (P < .001), BAL/serum ratios were significantly lower in SA compared to HC and MA (P < .001). Reduced SP-D levels in in BAL with concomitant rises in serum in SA were associated with degraded fragments of SP-D in the serum and increased BAL neutrophils and lipopolysaccharide levels.

Conclusions: These findings suggest defective innate immunity within the airways in severe asthma, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in severe asthmatics may provide a peripheral blood biomarker reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.

Text
__soton.ac.uk_ude_personalfiles_users_rae1d06_mydesktop_Mackay RM.pdf - Accepted Manuscript
Download (643kB)

More information

Accepted/In Press date: 12 November 2015
e-pub ahead of print date: 13 January 2016
Published date: May 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 384477
URI: https://eprints.soton.ac.uk/id/eprint/384477
ISSN: 0012-3692
PURE UUID: 86246fa2-8bf5-46f5-a2d2-88fcd08da963
ORCID for R-M. Mackay: ORCID iD orcid.org/0000-0002-9493-9654
ORCID for C. Barber: ORCID iD orcid.org/0000-0001-5335-5129

Catalogue record

Date deposited: 04 Jan 2016 14:36
Last modified: 10 Dec 2019 01:42

Export record

Altmetrics

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 https://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.

×