title: 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.
authors.affiliation: Allergy and Inflammation Sciences, University of Southampton, Southampton, UK. mich.lajeunesse@soton.ac.uk
authors.forename: Michel D S
authors.initials: MD
authors.lastname: Erlewyn-Lajeunesse
authors.forename: Linda P
authors.initials: LP
authors.lastname: Hunt
authors.forename: Petr
authors.initials: P
authors.lastname: Pohunek
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dobson
authors.forename: Puja
authors.initials: P
authors.lastname: Kochhar
authors.forename: Jane A
authors.initials: JA
authors.lastname: Warner
authors.forename: John O
authors.initials: JO
authors.lastname: Warner
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012135:Respiratory Sounds / Q000503:physiopathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9