Am. J. Respir. Crit. Care Med., Volume 159, Number 2, February 1999, 596-602

Serum Matrix Metalloproteinase-9:Tissue Inhibitor of Metalloproteinase-1 Ratio Correlates with Steroid Responsiveness in Moderate to Severe Asthma

MARC BOSSÉ, JAMILA CHAKIR, MAHMOUD ROUABHIA, LOUIS-PHILIPPE BOULET, MARIE AUDETTE, and MICHEL LAVIOLETTE

Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Laboratoire d'Organogénèse Expérimentale, Hôpital St-Sacrement, and Laboratoire d'Endocrinologie Moléculaire, Centre Hospitalier de l'Université Laval, Université Laval, Ste-Foy, Québec, Canada

Asthma presents a variable clinical response to corticosteroids (CS). Because CS more likely act on inflammation than on tissue remodeling, the presence of bronchial structural changes in certain asthmatics may explain their limited clinical response to CS. Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are, respectively, involved in tissue inflammatory processes and fibrogenic processes. Previous reports have suggested that MMP-9:TIMP-1 ratio may reflect the balance between these two processes in various diseases. This study evaluated the relation of this ratio and the response to CS in severe asthma. Twenty asthmatics with low baseline FEV₁ (59 ± 4% predicted) and  30 % increase with ₂-agonist were recruited. Serum MMP-9 and TIMP-1 levels were measured and correlated with response to an oral CS trial (methylprenisolone 40 mg/d for 14 d). With oral CS, FEV₁ changes (FEV₁) ranged from 15 to +43%. The FEV₁ closely correlated with the MMP-9:TIMP-1 ratios (rho = 0.79, p = 0.0006). In conclusion, serum MMP-9: TIMP-1 ratio could predict the response of oral CS therapy in asthma. The low MMP-9:TIMP-1 ratio observed in subjects with little or no FEV₁ improvement with CS supports the hypothesis that, in these asthmatic subjects, bronchial fibrogenesis predominates over inflammation.

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