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)
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
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- Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Primary Care & Population Sciences (pre 2018 reorg)
Current Faculties > Faculty of Medicine > Primary Care, Population Sciences and Medical Education > Primary Care & Population Sciences (pre 2018 reorg)
Primary Care, Population Sciences and Medical Education > Primary Care & Population Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Innate Immunology
Clinical and Experimental Sciences > Innate Immunology - Faculties (pre 2011 reorg) > Faculty of Medicine Health & Life Sciences (pre 2011 reorg) > Medicine (pre 2011 reorg)
Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Medicine (pre 2011 reorg) - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Institute for Life Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg)
Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Respiratory
Clinical and Experimental Sciences > Respiratory - Current Faculties > Faculty of Environmental and Life Sciences > School of Health Sciences > Nursing, Midwifery and Health > Adult Health
School of Health Sciences > Nursing, Midwifery and Health > Adult Health - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Clinical & Experimental Sciences (pre 2018 reorg)
Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg)
Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences
Clinical and Experimental Sciences
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