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


OBJECTIVE
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.
Respiratory Medicine, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, G12 OYN Scotland, United Kingdom.
Rekha
R
Chaudhuri
Charles
C
McSharry
Jeffrey
J
Brady
Iona
I
Donnelly
Christal
C
Grierson
Stephen
S
McGuinness
Lisa
L
Jolly
Christopher J
CJ
Weir
C Martina
CM
Messow
Mark
M
Spears
Gino
G
Miele
Karl
K
Nocka
Dan
D
Crowther
Joyce
J
Thompson
Maureen
M
Brannigan
Jane
J
Lafferty
Michael
M
Sproule
William
W
Macnee
Martin
M
Connell
John T
JT
Murchison
Malcolm C
MC
Shepherd
Giora
G
Feuerstein
Douglas K
DK
Miller
Neil C
NC
Thomson
D000328:Adult; D000368:Aged; D001249:Asthma / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004646:Emphysema / Q000175:diagnosis / Q000201:enzymology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013183:Sputum / Q000201:enzymology*; D014057:Tomography, X-Ray Computed
D053508:Matrix Metalloproteinase 12