PMID- 27460105 OWN - NLM STAT- MEDLINE DCOM- 20171129 LR - 20220408 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 17 IP - 1 DP - 2016 Jul 26 TI - Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases. PG - 92 LID - 10.1186/s12931-016-0402-z [doi] LID - 92 AB - 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 . FAU - Ostridge, Kristoffer AU - Ostridge K AUID- ORCID: 0000-0001-8910-3900 AD - Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. FAU - Williams, Nicholas AU - Williams N AD - Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. FAU - Kim, Viktoriya AU - Kim V AD - Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. FAU - Harden, Stephen AU - Harden S AD - Department of Radiology, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Bourne, Simon AU - Bourne S AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. FAU - Coombs, Ngaire A AU - Coombs NA AD - Primary Care & Population Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Elkington, Paul T AU - Elkington PT AD - Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. FAU - Estepar, Raul San Jose AU - Estepar RS AD - Department of Radiology, Laboratory of Mathematics in Imaging, Brigham and Women's Hospital, Boston, MA, USA. FAU - Washko, George AU - Washko G AD - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. FAU - Staples, Karl J AU - Staples KJ AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. AD - Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. FAU - Wilkinson, Tom M A AU - Wilkinson TM AD - Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. t.wilkinson@soton.ac.uk. AD - Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Mailpoint 810, Tremona Road, Southampton, SO16 6YD, UK. t.wilkinson@soton.ac.uk. AD - Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. t.wilkinson@soton.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT01701869 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160726 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (TIMP1 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Aged MH - Airway Obstruction/diagnostic imaging/etiology MH - Bronchoalveolar Lavage Fluid/chemistry MH - Bronchoscopy MH - Female MH - Humans MH - Lung/*enzymology MH - Male MH - Matrix Metalloproteinase Inhibitors/pharmacology MH - Matrix Metalloproteinases/*metabolism MH - Middle Aged MH - Pulmonary Disease, Chronic Obstructive/diagnostic imaging/enzymology MH - Pulmonary Emphysema/*diagnostic imaging/*enzymology MH - Respiratory Function Tests MH - Smoking/adverse effects MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Tomography, X-Ray Computed PMC - PMC4962504 OTO - NOTNLM OT - COPD OT - CT OT - Emphysema OT - Imaging OT - MMPs EDAT- 2016/07/28 06:00 MHDA- 2017/12/01 06:00 PMCR- 2016/07/26 CRDT- 2016/07/28 06:00 PHST- 2016/06/07 00:00 [received] PHST- 2016/07/09 00:00 [accepted] PHST- 2016/07/28 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/12/01 06:00 [medline] PHST- 2016/07/26 00:00 [pmc-release] AID - 10.1186/s12931-016-0402-z [pii] AID - 402 [pii] AID - 10.1186/s12931-016-0402-z [doi] PST - epublish SO - Respir Res. 2016 Jul 26;17(1):92. doi: 10.1186/s12931-016-0402-z.