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Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD

Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
Background
Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.

Objectives
We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls.

Methods
We analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease.

Results
Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways.

Conclusions
Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD.

Trial registration number NCT01701869
0040-6376
126-132
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Williams, Nicholas
00ee9f78-fdc9-434f-be3e-5ded7a8abe08
Kim, Viktoriya
b817634d-be5c-4cc4-a695-5eecf825114c
Bennett, Michael
6df5585a-3d93-4870-8797-389759fc82c7
Harden, Stephen
f53e511e-df8b-451f-aa1e-e8e80e1a4e46
Welch, Lindsay
bb0e5cbe-749d-476b-8251-3534e083cd0b
Bourne, Simon
b5efbc3f-70be-426f-9d45-9015bb90c8b3
Coombs, Ngaire A.
cf58008c-789e-484c-a567-842c1efc4e42
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Williams, Nicholas
00ee9f78-fdc9-434f-be3e-5ded7a8abe08
Kim, Viktoriya
b817634d-be5c-4cc4-a695-5eecf825114c
Bennett, Michael
6df5585a-3d93-4870-8797-389759fc82c7
Harden, Stephen
f53e511e-df8b-451f-aa1e-e8e80e1a4e46
Welch, Lindsay
bb0e5cbe-749d-476b-8251-3534e083cd0b
Bourne, Simon
b5efbc3f-70be-426f-9d45-9015bb90c8b3
Coombs, Ngaire A.
cf58008c-789e-484c-a567-842c1efc4e42
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652

Ostridge, Kristoffer, Williams, Nicholas, Kim, Viktoriya, Bennett, Michael, Harden, Stephen, Welch, Lindsay, Bourne, Simon, Coombs, Ngaire A., Elkington, Paul T., Staples, Karl J. and Wilkinson, Tom M.A. (2016) Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD. Thorax, 71 (2), 126-132. (doi:10.1136/thoraxjnl-2015-207428). (PMID:26645414)

Record type: Article

Abstract

Background
Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.

Objectives
We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls.

Methods
We analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease.

Results
Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways.

Conclusions
Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD.

Trial registration number NCT01701869

Text
Relationship between Pulmonary Matrix Metalloproteinases and Quantitative CT Markers of Small Airways Disease and Emphysema in COPD accepted.pdf - Accepted Manuscript
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More information

Accepted/In Press date: 9 November 2015
e-pub ahead of print date: 8 December 2015
Published date: February 2016
Organisations: Faculty of Health Sciences, Primary Care & Population Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 385040
URI: https://eprints.soton.ac.uk/id/eprint/385040
ISSN: 0040-6376
PURE UUID: 3462a1e1-b631-4412-a3eb-73dd5f19b4dc
ORCID for Lindsay Welch: ORCID iD orcid.org/0000-0001-5564-2252
ORCID for Paul T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

Catalogue record

Date deposited: 23 Dec 2015 14:38
Last modified: 12 Nov 2019 02:07

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