RESUMEN
Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation may be associated with an imbalance between these enzymes. MMP-9 and TIMP-1 concentrations were greater in sputum of patients with asthma and chronic bronchitis than in control subjects. The molar ratio between MMP-9 and TIMP-1 was lower in asthmatics and chronic bronchitics than in control subjects, and positively correlated with FEV1 values. In asthma, MMP-9 levels were significantly correlated with the number of macrophages and neutrophils. This study shows that airway inflammation in asthma and chronic bronchitis is associated with an imbalance between MMP-9 and TIMP-1 which may have a role in the pathogenesis of ECM remodeling and airflow obstruction.
Asunto(s)
Obstrucción de las Vías Aéreas/metabolismo , Asma/metabolismo , Bronquitis/metabolismo , Colagenasas/análisis , Inhibidores de Proteasas/análisis , Esputo/química , Inhibidor Tisular de Metaloproteinasa-1/análisis , Adolescente , Adulto , Anciano , Obstrucción de las Vías Aéreas/enzimología , Obstrucción de las Vías Aéreas/patología , Obstrucción de las Vías Aéreas/fisiopatología , Asma/enzimología , Asma/patología , Asma/fisiopatología , Bronquitis/enzimología , Bronquitis/patología , Bronquitis/fisiopatología , Recuento de Células , Enfermedad Crónica , Colágeno/metabolismo , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Matriz Extracelular/metabolismo , Volumen Espiratorio Forzado/fisiología , Homeostasis/fisiología , Humanos , Recuento de Leucocitos , Macrófagos/patología , Metaloproteinasa 9 de la Matriz , Persona de Mediana Edad , Neutrófilos/patología , Ventilación Pulmonar/fisiología , Dodecil Sulfato de Sodio , Esputo/citología , Esputo/enzimología , TensoactivosRESUMEN
The aim of this study was to evaluate the role of ageing on variability of airflow obstruction and on the specific pattern of nocturnal exacerbations ("morning dipping" of peak expiratory flow (PEF)) in asthma. Two groups of stable asthmatics (Group A: 23 patients, aged 14-47 yrs; Group B: 20 patients, aged 53-74 yrs), that were similar for duration of disease, degree of obstruction and response to bronchodilators, were studied. PEF was monitored four times daily for 2 weeks, and amplitude of variation and "morning dip" were calculated. Both PEF amplitude and "morning dip" were greater in the older patients (p<0.005). Amplitude was negatively correlated with baseline forced expiratory volume in one second (FEV1) in both groups (p<0.01); multiple correlation with age, duration of disease, baseline FEV1 and degree of reversibility was significant in the older group only. Morning dip was inversely correlated to baseline FEV1 (p<0.01) and reversibility (p<0.05). Nocturnal symptoms were reported by all of the five Group A "dippers", but by only 6 of the 13 Group B "dippers" (p<0.04). Ageing contributes to increased variability of airway calibre in asthma. Aged patients are potentially at risk because functional evidence of nocturnal asthma may frequently be accompanied by a poor subjective awareness. Therefore, a more extensive practice of PEF monitoring is recommended in aged asthmatics.