Kristoffer Ostridge1, Nicholas Williams1, Viktoriya Kim1, Michael Bennett2, Stephen Harden3, Lindsay Welch2, Simon Bourne4, Ngaire A Coombs5, Paul T Elkington1, Karl J Staples6, Tom M A Wilkinson7. 1. 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. 2. Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK. 3. Department of Radiology, University Hospital Southampton, Southampton General Hospital, Southampton, UK. 4. Department of Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. 5. Department of Primary Care & Population Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. 6. 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. 7. 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.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Lisa Öberg; Bastian Angermann; Alastair Watson; C Mirella Spalluto; Michael Hühn; Hannah Burke; Doriana Cellura; Anna Freeman; Daniel Muthas; Damla Etal; Graham Belfield; Fredrik Karlsson; Karl Nordström; Kris Ostridge; Karl J Staples; Tom Wilkinson Journal: Respir Res Date: 2021-05-29
Authors: Sara Brilha; Tarangini Sathyamoorthy; Laura H Stuttaford; Naomi F Walker; Robert J Wilkinson; Shivani Singh; Rachel C Moores; Paul T Elkington; Jon S Friedland Journal: Am J Respir Cell Mol Biol Date: 2017-02 Impact factor: 6.914
Authors: Dan Hameiri-Bowen; Evgeniya Sovershaeva; Trond Flaegstad; Tore Jarl Gutteberg; Lucky Gift Ngwira; Victoria Simms; Andrea M Rehman; Grace Mchugh; Tsitsi Bandason; Rashida Abbas Ferrand; Sarah Rowland-Jones; Louis-Marie Yindom Journal: AIDS Date: 2021-09-01 Impact factor: 4.632
Authors: Kristoffer Ostridge; Nicholas Williams; Viktoriya Kim; Stephen Harden; Simon Bourne; Ngaire A Coombs; Paul T Elkington; Raul San Jose Estepar; George Washko; Karl J Staples; Tom M A Wilkinson Journal: Respir Res Date: 2016-07-26