Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity

Chaudhuri, R. et al. (2012) Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity. Journal of Allergy and Clinical Immunology, 129(3), 665-663.e8. (doi: 10.1016/j.jaci.2011.12.996)

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Abstract

<br>Background:</br> <p> 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.</p> <br>Objectives:</br> <p> 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.</p> <br>Methods:</br> <p> 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)</p> <br>Results:</br> <p> 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.</p> <br>Conclusions:</br> <p> 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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Messow, Dr Martina and Thomson, Professor Neil and Jolly, Miss Lisa and Weir, Christopher and Spears, Dr Mark and Thompson, Mrs Joyce and Brannigan, Mrs Maureen and Chaudhuri, Dr Rekha and Lafferty, Mrs Jane and Donnelly, Mrs Iona and McSharry, Dr Charles and Shepherd, Professor Malcolm
Authors: Chaudhuri, R., McSharry, C., Brady, J., Donnelly, I., Grierson, C., McGuinness, S., Jolly, L., Weir, C.J., Messow, C.M., Spears, M., Miele, G., Nocka, K., Crowther, D., Thompson, J., Brannigan, M., Lafferty, J., Sproule, M., MacNee, W., Connell, M., Murchison, J.T., Shepherd, M., Feuerstein, G., Miller, D.K., and Thomson, N.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Allergy and Clinical Immunology
Journal Abbr.:J. Allergy Clin. Immunol.
ISSN:0091-6749
ISSN (Online):1097-6825
Published Online:01 February 2012

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