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5参Matrix Metalloproteinase-9 Expression
Matrix Metalloproteinase-9 Expression
in Asthma*
Effect of Asthma Severity, Allergen Challenge, and
Inhaled Corticosteroids
Waldo Mattos, MD; Sam Lim, MBBS; Richard Russell, MB;
Anon Jatakanon, MD; K. Fan Chung, MD, FCCP; and Peter J. Barnes, DM
Background: Asthma is associated with remodeling of the extracellular matrix (ECM) and
increased airway obstruction, and the mechanisms of this process are unknown. Matrix metallo-
proteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released
along with their inhibitors, tissue inhibitor of MMP (TIMP).
Study objectives: To determine whether severe, persistent asthma is associated with increased
levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both
allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels.
Design: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and
induced sputum obtained from asthmatics of differing disease severity. In patients with mild
asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge
and in BALF after inhaled steroid therapy.
Patients: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking,
atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent
allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks
treatment with inhaled budesonide, 800 g bid, or placebo.
Results: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their
sputum compared with patients with mild asthma and normal subjects. Allergen challenge
increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on
MMP-9 or TIMP-1 in patients with mild asthma.
Conclusions: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma,
as concentrations are increased in severe, persistent asthma and following allergen chall
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