Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation.
OBJECTIVE
Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase-2 (matrix metalloproteinase-8 (MMP-8)) and gelatinase B (MMP-9). We investigated the activity of NE and the levels of MMP-8 and MMP-9 in a longitudinal setting at and after COPD exacerbation using a non-invasive technique, i.e., induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation.


METHODS
The study included healthy non-smokers (n=32), healthy smokers (n=28), patients with stable COPD (n=15), COPD patients with acute exacerbations (exa) (n=10) and their recovery (n=8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP-8 levels by immunofluorometry and MMP-9 levels by ELISA were analysed from induced sputum supernatants.


RESULTS
NE activity and the level of MMP-8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p < 0.0001; MMP-8: p < 0.001 and p < 0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity).


CONCLUSIONS
COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP-8, which can be detected from the induced sputum supernatants of these COPD patients.
Department of Medicine, Division of Pulmonary Medicine, University of Helsinki, Finland.
Helen
H
Ilumets
Paula H
PH
Rytilä
Anssi R
AR
Sovijärvi
Taina
T
Tervahartiala
Marjukka
M
Myllärniemi
Timo A
TA
Sorsa
Vuokko L
VL
Kinnula
D000368:Aged; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D012129:Respiratory Function Tests; D012907:Smoking / Q000503:physiopathology; D013183:Sputum / Q000166:cytology / Q000201:enzymology*
D019272:Leukocyte Elastase; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9