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

Rekha Chaudhuri, Charles McSharry, Jeffrey Brady, Iona Donnelly, Christal Grierson, Stephen McGuinness, Lisa Jolly, Christopher J. Weir, C. Martina Messow, Mark Spears, Gino Miele, Karl Nocka, Dan Crowther, Joyce Thompson, Maureen Brannigan, Jane Lafferty, Michael Sproule, William MacNee, Martin Connell, John T. MurchisonMalcolm C. Shepherd, Giora Feuerstein, Douglas K. Miller, Neil C. Thomson

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    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 2950 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. (J Allergy Clin Immunol 2012; 129: 655-63.)

    Original languageEnglish
    Pages (from-to)655-U106
    Number of pages17
    JournalJournal of Allergy and Clinical Immunology
    Issue number3
    Publication statusPublished - Mar 2012

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