Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity - 01/03/12
Corresponding author: Neil C. Thomson, MD, Respiratory Medicine, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, G12 OYN Scotland, United Kingdom.Abstract |
Background |
Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.
Objectives |
We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.
Methods |
In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).
Results |
Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.
Conclusions |
Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.
Le texte complet de cet article est disponible en PDF.Key words : Matrix metalloproteinase 12, tissue inhibitor of metalloproteinases 1 and 2, MMP12 expression, emphysema, chronic obstructive pulmonary disease, asthma, smoker
Abbreviations used : COPD, CT, Dlco, FRET, FVC, %LAA−950, MMP, qPCR, TIMP
Plan
| Supported by an award (INF-GU-090) from the Translational Medicine Research Collaboration, a consortium made up of the Universities of Glasgow, Edinburgh, Aberdeen, and Dundee and the 4 associated NHS Health Boards (Greater Glasgow & Clyde, Lothian, Grampian, and Tayside), Scottish Enterprise, and Pfizer (formerly Wyeth) and supported financially by NHS Research Scotland (NRS) through the Scottish Primary Care Research Network. |
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| Disclosure of potential conflict of interest: K. Nocka is employed by Pfizer. D. Crowther is a previous employee of Pfizer and is a visiting Fellow at the Cranfield University and an honorary lecturer at the University of Dundee. W. MacNee has received research support from Pfizer. D. K. Miller is a Pfizer/Wyeth employee. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 3
P. 655 - mars 2012 Retour au numéro
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