Bronchoalveolar Lavage MMP-9 and TIMP-1 in Preschool Wheezers and Their Relationship to Persistent Wheeze

Abstract

Atopic preschool children are more likely to develop persistent wheezing, which could be a consequence of early airway remodeling. Protease-antiprotease balance between MMP-9 and its cognate inhibitor TIMP-1 may be involved in this process. Our hypothesis was that atopic wheezing preschool children would have an imbalance of MMP-9 to TIMP-1 in bronchoalveolar lavage (BAL). BAL from 52 preschool wheezers was compared with 14 controls without wheeze. A subgroup completed an International Study of Asthma and Allergy in Childhood symptom questionnaire 2 y later. Molar ratios of MMP-9/TIMP-1 were higher in wheezy children (p < 0.001; median 4.0%, range 0-8.7) than controls (0.6%, 0-1.8), and showed an excess of TIMP-1 in the airway. BAL TIMP-1 was raised in children with persistent wheezing (p = 0.028; 34.4 ng/mL, 9.1-93.1 compared with 10.6 ng/mL 6.1-18.6), as was serum levels of intercellular adhesion molecule-1 (p = 0.027). The absolute concentration of TIMP-1 in the airway, rather than its molar ratio with MMP-9, was associated with persistent wheezing. The processes involved with airway remodeling are complex but excess TIMP-1 may impede matrix protein turnover and thereby contribute to persistent changes in airway structure and wheezing.