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

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)

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.<p></p> 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.<p></p> 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.<p></p> 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: Messow, Dr Martina and Thomson, Professor Neil and Spears, Dr Mark and Chaudhuri, Dr Rekha and McSharry, Dr Charles
• 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 Centre; College 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