Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma

Background: The balance between matrix metalloproteinase- 9 ( MMP- 9) and tissue inhibitor of metalloproteinase- 1 ( TIMP- 1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP- 1 over MMP- 9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic ( CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. Methods: Sputum levels of MMP- 9, TIMP- 1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area ( WA/ BSA), the ratio of WA to outer wall area ( WA%), and the absolute wall thickness corrected by root BSA of a segmental bronchus ( T/ ! BSA), was examined. Results: Sputum MMP- 9 levels were inversely correlated with WA% and TIMP- 1 levels were positively correlated with WA/ BSA and T/ root BSA. The MMP- 9/ TIMP- 1 molar ratio was inversely correlated with WA% and T/! BSA and positively correlated with post- bronchodilator values of mid- forced expiratory flow and maximum expiratory flow at the quartile of lung volume. Conclusion: Excess TIMP- 1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.