Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma (original) (raw)

Chaudhuri, R. et al. (2014) Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma.European Respiratory Journal, 44(4), pp. 895-904. (doi: 10.1183/09031936.00047014)

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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.

Item Type: Articles
Status: Published
Refereed: Yes
Glasgow Author(s) Enlighten ID: Spears, Dr Mark and Chaudhuri, Dr Rekha and Messow, Dr Martina and McSharry, Dr Charles and Thomson, Professor Neil
Authors: Chaudhuri, R., McSharry, C., Brady, J., Grierson, C., Messow, C.M., Spears, M., Miele, G., Nocka, K., MacNee, W., Connell, M., Murchison, J. T., Sproule, M., Hilmi, O. J., Miller, D. K., and Thomson, N. C.
College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson CentreCollege of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name: European Respiratory Journal
Publisher: European Respiratory Society
ISSN: 0903-1936
ISSN (Online): 1399-3003

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Deposit and Record Details

ID Code: 98821
Depositing User: Miss Fiona Doyle
Datestamp: 03 Nov 2014 12:38
Last Modified: 02 May 2025 03:38
Date of first online publication: 1 October 2014