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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)655-663.e8
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Matrix metalloproteinase 12
  • tissue inhibitor of metalloproteinases 1 and 2
  • MMP12 expression
  • emphysema
  • chronic obstructive pulmonary disease
  • asthma
  • smoker

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