title: Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD.
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.
  
  
  OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01701869.
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Kristoffer
authors.identifier: http://orcid.org/0000-0001-8910-3900
authors.initials: K
authors.lastname: Ostridge
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Williams
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Kim
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Department of Radiology, University Hospital Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harden
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Welch
authors.affiliation: Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Bourne
authors.affiliation: Department of Primary Care & Population Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Ngaire A
authors.initials: NA
authors.lastname: Coombs
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Elkington
authors.affiliation: Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Staples
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Tom M A
authors.initials: TM
authors.lastname: Wilkinson
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D013147:Spirometry; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020782:Matrix Metalloproteinases
keywords: COPD ÀÜ Mechanisms; Emphysema; Imaging/CT MRI etc; Lung Proteases