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

J Allergy Clin Immunol. 2012 Mar;129(3):655-663.e8. doi: 10.1016/j.jaci.2011.12.996. Epub 2012 Feb 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / complications
  • Asthma / diagnosis
  • Asthma / immunology*
  • Asthma / physiopathology*
  • Cross-Sectional Studies
  • Disease Progression
  • Emphysema / diagnosis
  • Emphysema / enzymology
  • Female
  • Fluorescence Resonance Energy Transfer
  • Follow-Up Studies
  • Humans
  • Male
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / immunology
  • Matrix Metalloproteinase 12 / metabolism*
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Respiratory Function Tests
  • Severity of Illness Index
  • Sputum / enzymology*
  • Tomography, X-Ray Computed


  • Matrix Metalloproteinase 12