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A Comparison of Airway and Serum Matrix Metalloproteinase-9 Activity Among Normal Subjects, Asthmatic Patients, and Patients With Asthmatic Mucus Hypersecretion^*

^* From the Woolcock Institute of Medical Research (Drs. Ko, Roth, Johnson, Salome, and King, and Ms. Diba), University of Sydney, Sydney, NSW, Australia; and the Department of Respiratory Medicine (Dr. McKay), The Children’s Hospital at Westmead, Sydney, NSW, Australia.

Correspondence to: Gregory King, MB ChB, PhD, Woolcock Institute of Medical Research and Department of Respiratory Medicine, Royal North Shore Hospital, St. Leonards 2065, NSW, Australia; e-mail: ggk{at}woolcock.org.au

Background: The rate of decline in lung function is increased in asthmatic patients, particularly in those with coexisting asthmatic mucus hypersecretion (AMH), in whom inflammation and the activity of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in serum and BAL fluid (BALF) may be increased.

Methods: Seven nonasthmatic subjects and 22 asthmatic subjects completed a questionnaire, and underwent lung function testing and bronchoscopy, during which AMH was diagnosed by the presence of mucus plugging. Subjects were classified as follows: mild/moderate asthma; severe asthma; and AMH. In BALF, we measured the differential WBC counts and MMP-9 activity by zymography. We measured total MMP-9 and TIMP-1 activity by enzyme-linked immunosorbent assay in BALF and serum.

Results: The mean (± confidence interval) FEV₁ was lower in AMH patients (73 ± 13% predicted) compared with nonasthmatic subjects (95 ± 7%) and patients with mild/moderate asthma (73 ± 9%; p < 0.05), and was similar to that of patients with severe asthma (80 ± 20%). MMP-9 activity was greater in AMH patients and in patients with severe asthma compared with nonasthmatic subjects (p = 0.05 and p = 0.01, respectively), as were TIMP-1 activities (p = 0.001 and p = 0.04, respectively), but MMP-9/TIMP-1 ratios were not. MMP-9 activity increased across the four groups from nonasthmatic subjects to AMH patients (r = 0.58; p = 0.0009), but the differential and total WBC counts were similar. There were no relationships between FEV₁ percent predicted and either MMP-9 activity or MMP-9/TIMP-1 ratio. There were no differences in serum MMP-9 activity, which did not correlate with MMP-9 activity in BALF.

Conclusions: AMH and severe asthma were associated with greater proteolytic enzyme activities despite similar airway inflammation, which might play a role in remodeling and accelerated the decline in lung function in these patients.

Key Words: asthma • BAL fluid • matrix metalloproteinase • mucus hypersecretion

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