Sputum metalloproteinase-9 tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis

Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECR;I) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metallopro teinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We fi rst performed zymographic analysis to identify the profile of MMPs. Zymogra phy revealed a similar MMPs profile in all populations studied and that MMP -9 was the major enzyme released. We then measured, using enzyme immunoassa y, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated wh ether airflow limitation may be associated with an imbalance between these enzymes. MMP-9 and TIMP-1 concentrations were greater in sputum of patients with asthma and chronic bronchitis than in control subjects. The molar rat io between MMP-9 and TIMP-1 was lower in asthmatics and chronic bronchitics than in control subjects, and positively correlated with FEV1 values. In a sthma, MMP-9 levels were significantly correlated with the number of macrop hages and neutrophils. This study shows that airway inflammation in asthma and chronic bronchitis is associated with an imbalance between MMP-9 and TI MP-1 which may have a role in the pathogenesis of ECM remodeling and airflo w obstruction.