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Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases
Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases
BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.

METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.

RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.

CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.

TRIAL REGISTRATION: Trial registration number NCT01701869 .
COPD, emphysema, CT, imaging, MMPs
1465-9921
1-8
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Williams, Nicholas
00ee9f78-fdc9-434f-be3e-5ded7a8abe08
Kim, Viktoriya
714f98eb-2fa3-4a97-99f9-f7e7765ec128
Harden, Stephen
f53e511e-df8b-451f-aa1e-e8e80e1a4e46
Bourne, Simon
b5efbc3f-70be-426f-9d45-9015bb90c8b3
Coombs, Ngaire A.
49b76416-c94e-4b3e-8aef-d915ab1b60be
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Estepar, Raul San Jose
0d30dfca-18df-4367-8c1b-63770adf4c0d
Washko, George
52790667-8b88-4f29-bd57-158ff41b64d2
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
714f98eb-2fa3-4a97-99f9-f7e7765ec128
Harden, Stephen
f53e511e-df8b-451f-aa1e-e8e80e1a4e46
Bourne, Simon
b5efbc3f-70be-426f-9d45-9015bb90c8b3
Coombs, Ngaire A.
49b76416-c94e-4b3e-8aef-d915ab1b60be
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Estepar, Raul San Jose
0d30dfca-18df-4367-8c1b-63770adf4c0d
Washko, George
52790667-8b88-4f29-bd57-158ff41b64d2
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652

Ostridge, Kristoffer, Williams, Nicholas, Kim, Viktoriya, Harden, Stephen, Bourne, Simon, Coombs, Ngaire A., Elkington, Paul T., Estepar, Raul San Jose, Washko, George, Staples, Karl J. and Wilkinson, Tom M.A. (2016) Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases. Respiratory Research, 17 (92), 1-8. (doi:10.1186/s12931-016-0402-z). (PMID:27460105)

Record type: Article

Abstract

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.

METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.

RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.

CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.

TRIAL REGISTRATION: Trial registration number NCT01701869 .

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More information

Accepted/In Press date: 8 July 2016
e-pub ahead of print date: 26 July 2016
Published date: 26 July 2016
Keywords: COPD, emphysema, CT, imaging, MMPs
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 398748
URI: https://eprints.soton.ac.uk/id/eprint/398748
ISSN: 1465-9921
PURE UUID: e80a5bb3-c59d-436f-8bd0-983cd76b3492
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: 01 Aug 2016 12:07
Last modified: 03 Dec 2019 01:46

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