[Metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in induced sputum in patients with asthma and chronic obstructive pulmonary disease and their relationship to airway inflammation and airflow limitation].

OBJECTIVE

To investigate the levels of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in induced sputum in patients with asthma and chronic obstructive pulmonary disease (COPD), and its relationship to the number of inflammation cells and lung function.

METHODS

Fourteen patients with asthma in remission stages, 12 patients with stable COPD and 10 normal control subjects were included in this study. Lung function was measured. Induced sputum was obtained and processed for cell differential and the supernatant was assayed for the concentrations of interleukin-4 (IL-4), MMP-9 and TIMP-1 by enzyme-linked immunosorbent assay (ELISA).

RESULTS

The percentage of eosinophils in induced sputum in asthmatics (0.181 +/- 0.067) was significantly higher than that in normal control subjects (0.007 +/- 0.005) and in COPD (0.042 +/- 0.017, F = 4.32, P < 0.05). The percentage of neutrophils in induced sputum in patients with COPD (0.500 +/- 0.101) was significantly higher than that in asthmatics (0.30 +/- 0.07) and in normal control subjects (0.26 +/- 0.06, F = 4.13, P < 0.05). The concentrations of IL-4 in asthmatics, COPD and normal control subjects [respectively, (19 +/- 7) x 10(-3) g/L, (14 +/- 6) x 10(-3) g/L, (11 +/- 4) x 10(-3) g/L] did not show significant difference (F = 1.56, all P > 0.05) and did not correlate with the number of eosinophils (r = 0.33, 0.11, 0.19, all P > 0.05) and neutrophil (r = 0.25, 0.39, 0.40, all P > 0.05) and FEV(1) values (predicted r = 0.21, 0.35, 0.17, all P > 0.05). The concentrations of MMP-9 and TIMP-1 in induced sputum in asthmatics [(15.9 +/- 6.0) g/L, (19.8 +/- 8.5) g/L, respectively] and COPD [(13.4 +/- 5.1) g/L, (16.7 +/- 7.6) g/L, respectively] were significantly higher than those in normal control subjects [(1.8 +/- 1.1) g/L, (1.3 +/- 0.9) g/L, respectively] (F = 2.99, 4.22, respectively, all P < 0.05). Increased concentration of MMP-9 correlated positively with the percentage of eosinophils in asthmatics (r = 0.71, P < 0.05) and with the percentage of neutrophils in COPD (r = 0.59, P < 0.05), but did not correlate with FEV(1) values (predicted r = 0.22, 0.16, all P > 0.05) and FEV(1)/FVC (r = 0.25, 0.30, all P > 0.05). Increased concentration of TIMP-1 did not correlate with the number of eosinophils (r = 0.27, 0.31, all P > 0.05) and neutrophil (r = 0.20, 0.35, all P > 0.05) in asthmatics and COPD, but correlated inversely with FEV(1) values (predicted, respectively, r = -0.58, -0.62, all P < 0.05). The ratio of MMP-9/TIMP-1 was significantly lower in asthmatics 0.8 +/- 0.7 and COPD 0.8 +/- 0.6 than that in normal control subjects (1.5 +/- 0.6, F = 3.70, P < 0.05). The ratio was not statistically different between asthmatics and COPD (F = 1.78, P > 0.05). In asthmatics and COPD patients, the ratio of MMP-9/TIMP-1 in induced sputum correlated positively with FEV(1%) (respectively, r = 0.56, 0.61, all P < 0.05).

CONCLUSION

An imbalance between MMP-9 and TIMP-1 in induced sputum in asthmatics and COPD is associated with airway inflammation and airflow limitation, which may play a role in the pathogenesis of extracellular matrix remodeling and airflow limitation.