Markers of Airway Remodeling in Induced Sputum From Healthy Smokers

ObjectiveAirway 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.Patients and methodsSamples 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.ResultsCompared 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] ug/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.ConclusionsHealthy 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.

ObjetivoEl remodelado bronquial en la enfermedad pulmonar obstructiva crónica (EPOC) se ha relacionado con el equilibrio entre la metaloproitenasa (MMP) 9 y su inhibidor, el inhibidor tisular de MMP tipo 1 (TIMP-1). Dicho equilibrio no se ha analizado en fumadores sanos. Nuestro objetivo ha sido estudiar dicho equilibrio en el esputo inducido de fumadores sanos respecto a sanos no fumadores (controles) y pacientes con EPOC.Pacientes y métodosSe obtuvieron 35 muestras de esputo inducido, de las que 12 provenían de fumadores sanos, otras 12 de controles y 11 de pacientes con EPOC. Se estudiaron la celularidad de las muestras y la concentración de MMP-9 (total y fracción activa) y TIMP-1 mediante enzimoinmunoanálisis.ResultadosLos fumadores sanos mostraron mayor concentración media (± desviación estándar) de MMP-9 total (273 ± 277 ng/ml) y una ratio mayor (0,16 ± 0,14) que los controles (128 ± 146 ng/ml y 0,08 ± 0,06, respectivamente). Sin embargo, la ratio MMP-9 activa/TIMP-1 fue equiparable en ambos grupos. Los pacientes con EPOC mostraron los valores más altos de MMP-9 total (477 ± 262 ng/ml) y activa (178 ± 126 ng/ml) y los más bajos de TIMP-1 (1.044 ± 1.036 ng/ml). Globalmente, la ratio mostró una relación inversa con el volumen espiratorio forzado en el primer segundo. Dicha relación fue aún superior con la MMP-9 activa y con el grado de tabaquismo.ConclusionesLos fumadores sanos presentaron una mayor concentración de MMP-9 total en relación con el grado de exposición tabáquica. Una ratio MMP-9 activa/TIMP-1 conservada en fumadores sanos podría explicar la ausencia de obstrucción progresiva de la vía aérea. La medida de la MMP-9 activa puede ser útil en la determinación del remodelado bronquial.