Markers of airway remodeling in induced sputum from healthy smokers

Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD. Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1. Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] microg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered. Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling.