Bronchoalveolar lavage MMP-9 and TIMP-1 in preschool wheezers and their relationship to persistent wheeze

Pediatr Res. 2008 Aug;64(2):194-9. doi: 10.1203/PDR.0b013e318175dd2d.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid*
  • Case-Control Studies
  • Child, Preschool
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Health Surveys
  • Humans
  • Infant
  • Intercellular Adhesion Molecule-1 / blood
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Respiratory Sounds / physiopathology*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 9