A low sputum MMP-9 activity/TIMP ratio is associated with CT airway wall thickness in smokers with asthma

BACKGROUND In asthma, smokers have severe symptoms and decreased sensitivity to corticosteroids. A reduced matrix-metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) ratio in asthma has been implicated in airway remodelling and steroid resistance. Our hypothesis is that sputum MMP-9/TIMPs are reduced in smokers with asthma and are associated with measures of airway remodelling. METHODS In 98 asthmatics and 44 controls (smokers & non-smokers) we measured sputum MMP-9 activity & concentrations and TIMP1/2 levels, diffusing capacity for carbon monoxide (DLCO) and CT airway wall thickness (RB10% wall area). RESULTS Sputum MMP-9 activity/TIMPs-1 and 2 were lower in smokers with asthma compared with non-smokers and in healthy smokers vs non-smokers (Table 1). Sputum MMP-9/TIMP correlated with sputum % neutrophils, but not with DLCO. In smokers with asthma, reduced sputum MMP-9 activity/TIMP1 was associated with increased RB10 % wall area [correlation coefficient [-0.45 (-0.71, -0.09)]. CONCLUSION A low sputum MMP-9 activity/TIMP1 ratio is associated with airway wall thickness in smokers with asthma, suggesting a potential role for MMP-9 and TIMP in airway remodelling in this group.