Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma : Relationship to disease severity. / Chaudhuri, Rekha; McSharry, Charles; Brady, Jeffrey; Donnelly, Iona; Grierson, Christal; McGuinness, Stephen; Jolly, Lisa; Weir, Christopher J.; Messow, C. Martina; Spears, Mark; Miele, Gino; Nocka, Karl; Crowther, Dan; Thompson, Joyce; Brannigan, Maureen; Lafferty, Jane; Sproule, Michael; MacNee, William; Connell, Martin; Murchison, John T.; Shepherd, Malcolm C.; Feuerstein, Giora; Miller, Douglas K.; Thomson, Neil C.
In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 3, 03.2012, p. 655-U106.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma
T2 - Relationship to disease severity
A1 - Chaudhuri,Rekha
A1 - McSharry,Charles
A1 - Brady,Jeffrey
A1 - Donnelly,Iona
A1 - Grierson,Christal
A1 - McGuinness,Stephen
A1 - Jolly,Lisa
A1 - Weir,Christopher J.
A1 - Messow,C. Martina
A1 - Spears,Mark
A1 - Miele,Gino
A1 - Nocka,Karl
A1 - Crowther,Dan
A1 - Thompson,Joyce
A1 - Brannigan,Maureen
A1 - Lafferty,Jane
A1 - Sproule,Michael
A1 - MacNee,William
A1 - Connell,Martin
A1 - Murchison,John T.
A1 - Shepherd,Malcolm C.
A1 - Feuerstein,Giora
A1 - Miller,Douglas K.
A1 - Thomson,Neil C.
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 - <p>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.</p><p>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).</p><p>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.</p><p>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.)</p>
AB - <p>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.</p><p>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).</p><p>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.</p><p>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.)</p>
U2 - 10.1016/j.jaci.2011.12.996
DO - 10.1016/j.jaci.2011.12.996
M1 - Article
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
VL - 129
SP - 655-U106
ER -