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Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma

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

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Authors

  • 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. Murchison
  • And 4 others
  • Malcolm C. Shepherd
  • Giora Feuerstein
  • Douglas K. Miller
  • Neil C. Thomson

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Info

Original languageEnglish
Pages655-U106
Number of pages17
JournalJournal of Allergy and Clinical Immunology
Journal publication dateMar 2012
Volume129
Issue3
DOIs
StatePublished

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 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.)

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