Serum matrix metalloproteinase-9: Tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma

Asthma presents a variable clinical response to corticosteroids (CS). Becau se CS more likely act on inflammation than on tissue remodeling, the presen ce 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-l (TIMP-1), are, respecti vely, involved in tissue inflammatory processes and fibrogenic processes. P revious reports have suggested that MMP-9:TIMP-1 ratio may reflect the bala nce between these two processes in various diseases. This study evaluated t he relation of this ratio and the response to CS in severe asthma. Twenty a sthmatics with low baseline FEV1 (59 +/- 4% predicted) and greater than or equal to 30 % increase with beta(2)-agonist were recruited. Serum MMP-9 and TIMP-1 levels were measured and correlated with response to an oral CS tri al (methylprenisolone 40 mg/d for 14 d). With oral CS, FEV1 changes (Delta FEV1) ranged from -15 to +43%. The Delta FEV1 closely correlated with the M MP-9:TIMP-1 ratios (rho = 0.79, p = 0.0006). In conclusion, serum MMP-9: TI MP-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, bronchi al fibrogenesis predominates over inflammation.