title: Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma.
abstract: Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions. Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls. Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area. The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK rekhachaudhuri@yahoo.com.
authors.forename: Rekha
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brady
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.
authors.forename: Christal
authors.initials: C
authors.lastname: Grierson
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: C Martina
authors.initials: CM
authors.lastname: Messow
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Spears
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Cambridge MA, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Nocka
authors.affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, UK.
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Connell
authors.affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: Murchison
authors.affiliation: Radiology Dept, Gartnavel General Hospital, Glasgow, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Sproule
authors.affiliation: Ear Nose and Throat Dept, Gartnavel General Hospital, Glasgow, UK.
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Hilmi
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Miller
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology*; D001995:Bronchography / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*; D014057:Tomography, X-Ray Computed
chemical_list: C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9