title: Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma.
abstract: 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 radicalBSA of a segmental bronchus (T/ radicalBSA), was examined.
  
  
  RESULTS
  Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/ radicalBSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/ radicalBSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume.
  
  
  CONCLUSIONS
  Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Niimi
authors.forename: M
authors.initials: M
authors.lastname: Takemura
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Minakuchi
authors.forename: R
authors.initials: R
authors.lastname: Tabuena
authors.forename: K
authors.initials: K
authors.lastname: Chin
authors.forename: T
authors.initials: T
authors.lastname: Mio
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Muro
authors.forename: T
authors.initials: T
authors.lastname: Hirai
authors.forename: S
authors.initials: S
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
authors.forename: M
authors.initials: M
authors.lastname: Mishima
mesh_terms: D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000473:pathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D013183:Sputum / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014057:Tomography, X-Ray Computed / Q000379:methods; D014797:Vital Capacity / Q000502:physiology
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9