PT  - JOURNAL ARTICLE
AU  - Kristoffer Ostridge
AU  - Nicholas Williams
AU  - Viktoriya Kim
AU  - Michael Bennett
AU  - Stephen Harden
AU  - Lindsay Welch
AU  - Simon Bourne
AU  - Ngaire A Coombs
AU  - Paul T Elkington
AU  - Karl J Staples
AU  - Tom MA Wilkinson
TI  - Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
AID  - 10.1136/thoraxjnl-2015-207428
DP  - 2016 Feb 01
TA  - Thorax
PG  - 126--132
VI  - 71
IP  - 2
4099  - http://thorax.bmj.com/content/71/2/126.short
4100  - http://thorax.bmj.com/content/71/2/126.full
SO  - Thorax2016 Feb 01; 71
AB  - 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