RT Journal Article
SR Electronic
T1 Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 895
OP 904
DO 10.1183/09031936.00047014
VO 44
IS 4
A1 Rekha Chaudhuri
A1 Charles McSharry
A1 Jeffrey Brady
A1 Christal Grierson
A1 C. Martina Messow
A1 Mark Spears
A1 Gino Miele
A1 Karl Nocka
A1 William MacNee
A1 Martin Connell
A1 John T. Murchison
A1 Michael Sproule
A1 Omar J. Hilmi
A1 Douglas K. Miller
A1 Neil C. Thomson
YR 2014
UL http://erj.ersjournals.com/content/44/4/895.abstract
AB 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. In asthmatic smokers, a low sputum MMP-9 activity/TIMP-1 is associated with spirometric and CT airway narrowing http://ow.ly/wnbAh