TY - JOUR
T1 - Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma
T2 - Relationship to disease severity
AU - Chaudhuri, Rekha
AU - McSharry, Charles
AU - Brady, Jeffrey
AU - Donnelly, Iona
AU - Grierson, Christal
AU - McGuinness, Stephen
AU - Jolly, Lisa
AU - Weir, Christopher J.
AU - Messow, C. Martina
AU - Spears, Mark
AU - Miele, Gino
AU - Nocka, Karl
AU - Crowther, Dan
AU - Thompson, Joyce
AU - Brannigan, Maureen
AU - Lafferty, Jane
AU - Sproule, Michael
AU - MacNee, William
AU - Connell, Martin
AU - Murchison, John T.
AU - Shepherd, Malcolm C.
AU - Feuerstein, Giora
AU - Miller, Douglas K.
AU - Thomson, Neil C.
PY - 2012/3
Y1 - 2012/3
N2 - 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.)
AB - 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.)
U2 - 10.1016/j.jaci.2011.12.996
DO - 10.1016/j.jaci.2011.12.996
M3 - Article
C2 - 22305682
SN - 0091-6749
VL - 129
SP - 655-U106
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -