RESUMEN
PURPOSE: Mucolytics can improve disease outcome in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The objectives of this study were to investigate the effects of erdosteine (ER), a mucolytic agent with antioxidant activity, on systemic inflammation, symptoms, recurrence of exacerbation, and time to first exacerbation postdischarge in hospitalized patients with AECOPD. PATIENTS AND METHODS: Patients admitted to hospital with AECOPD were randomized to receive either ER 900 mg daily (n=20) or a matching control (n=20). Treatment was continued for 10 days until discharge. Patients also received standard treatment with steroids, nebulized bronchodilators, and antibiotics as appropriate. Serum C-reactive protein levels, lung function, and breathlessness-cough-sputum scale were measured on hospital admission and thereafter at days 10 and 30 posttreatment. Recurrence of AECOPD-requiring antibiotics and/or oral steroids and time to first exacerbation in the 2 months (days 30 and 60) postdischarge were also assessed. RESULTS: Mean serum C-reactive protein levels were lower in both groups at days 10 and 30, compared with those on admission, with significantly lower levels in the ER group at day 10. Improvements in symptom score and forced expiratory volume in 1 second were greater in the ER than the control group, which reached statistical significance on day 10. ER was associated with a 39% lower risk of exacerbations and a significant delay in time to first exacerbation (log-rank test P=0.009 and 0.075 at days 30 and 60, respectively) compared with controls. CONCLUSION: Results confirm that the addition of ER (900 mg/d) to standard treatment improves outcomes in patients with AECOPD. ER significantly reduced airway inflammation, improved the symptoms of AECOPD, and prolonged time to first exacerbation. The authors suggest ER could be most beneficial in patients with recurring, prolonged, and/or severe exacerbations of COPD.
Asunto(s)
Antiinflamatorios/administración & dosificación , Expectorantes/administración & dosificación , Alta del Paciente , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Tioglicolatos/administración & dosificación , Tiofenos/administración & dosificación , Adulto , Anciano , Antiinflamatorios/efectos adversos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Progresión de la Enfermedad , Esquema de Medicación , Expectorantes/efectos adversos , Femenino , Volumen Espiratorio Forzado , Humanos , Mediadores de Inflamación/sangre , Italia , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Recuperación de la Función , Recurrencia , Método Simple Ciego , Tioglicolatos/efectos adversos , Tiofenos/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation, which is largely irreversible; the oxidant/antioxidant imbalance is important in the pathogenesis of this condition. OBJECTIVE: To show that administration of erdosteine, a mucolytic agent with a prevalent antioxidant activity, could play a beneficial role in COPD. METHODS: To review the experimental and clinical trials on erdosteine in COPD and chronic bronchitis. RESULTS: Erdosteine is a thiol agent with a multifactorial mechanism of action, namely: mucolytic, antibacterial, antioxidant and anti-inflammatory activity. In the acute exacerbation of chronic bronchitis/COPD, addition of erdosteine 300 mg twice a day for 7 - 10 days to standard treatment improves the symptoms and reduces the time of disease. In clinically stable COPD, long-term treatment is associated with a reduction in acute exacerbation and hospitalization rate and a significant improvement of quality of life. Erdosteine could be most beneficial in patients who have repeated, prolonged or severe exacerbations of COPD.
Asunto(s)
Expectorantes/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Tioglicolatos/uso terapéutico , Tiofenos/uso terapéutico , Animales , Antioxidantes/efectos adversos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Bronquitis/tratamiento farmacológico , Ensayos Clínicos como Asunto , Expectorantes/efectos adversos , Expectorantes/farmacología , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Índice de Severidad de la Enfermedad , Tioglicolatos/efectos adversos , Tioglicolatos/farmacología , Tiofenos/efectos adversos , Tiofenos/farmacologíaRESUMEN
Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and antioxidant activity too. There are several experimental evidences which support the protective effect of erdosteine in acute injury induced by a variety of pharmacological or noxious agents, mediated by products of oxidative stress. Experimental data in animal assigned to receive the noxious agent evidence that co-treatment with erdosteine increases the tissue antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase, compared with the toxic agent alone; meanwhile erdosteine decreases the tissue level of nitric oxide, xanthine oxidase, which catalyze oxygen-free radical production. In summary, erdosteine prevents the accumulation of free oxygen radicals when their production is accelerated and increases antioxidant cellular protective mechanisms. The final result is a protective effect on tissues which reduces lipid peroxidation, neutrophil infiltration or cell apoptosis mediated by noxious agents. Recent positive clinical trials in humans seem to fulfill the impressive promises that theory and experimental research have put forward.
Asunto(s)
Antioxidantes/farmacología , Enfermedades Pulmonares/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Fármacos del Sistema Respiratorio/farmacología , Tioglicolatos/farmacología , Tiofenos/farmacología , Animales , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Peroxidación de Lípido/efectos de los fármacos , Enfermedades Pulmonares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fármacos del Sistema Respiratorio/uso terapéutico , Tioglicolatos/uso terapéutico , Tiofenos/uso terapéuticoRESUMEN
Erdosteine is a multimechanism, mucolytic agent that decreases the sputum viscoelastic properties and bacterial adhesion to the cell membrane, endowed with bronchial anti-inflammatory activity and a scavenging effect on free oxidant radicals. Erdosteine is a prodrug and metabolite I is the active metabolite of erdosteine owing to its free thiol group. In acute infective exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (COPD), adding erdosteine to standard treatment significantly modified the outcome by improving the symptoms and reducing the length of disease. Furthermore, erdosteine has shown a synergism with antibiotic therapy. In stable COPD patients, long-term treatment with erdosteine had a protective effect against exacerbations by reducing the rate of exacerbations and hospitalizations in the study period. A total of 8 months of treatment with erdosteine significantly improved the patients' health status and preserved lung function. Erdosteine has a scavenging effect on free oxidant radicals by a direct and indirect antioxidative effect and the final result is a protective effect against tissue damage, as demonstrated in animal studies. In view of the persuasive evidence that oxidative stress is important in the pathophysiology of COPD, erdosteine appears to be a logical approach to therapy.
RESUMEN
OBJECTIVE: To investigate whether the addition of intrapulmonary percussive ventilation to the usual chest physiotherapy improves gas exchange and lung mechanics in tracheostomized patients. DESIGN AND SETTING: Randomized multicenter trial in two weaning centers in northern Italy. PATIENTS AND PARTICIPANTS: 46 tracheostomized patients (age 70 +/- 7 years, 28 men, arterial blood pH 7.436 +/- 0.06, PaO(2)/FIO(2) 238 +/- 46) weaned from mechanical ventilation. INTERVENTIONS: Patients were assigned to two treatment groups performing chest physiotherapy (control), or percussive ventilation (IMP2 Breas, Sweden) 10 min twice/day in addition to chest physiotherapy (intervention). MEASUREMENTS AND RESULTS: Arterial blood gases, PaO(2)/FIO(2) ratio, and maximal expiratory pressure were assessed every 5th day for 15 day. Treatment complications that showed up in 1 month of follow-up were recorded. At 15 days the intervention group had a significantly better PaO(2)/FIO(2) ratio and higher maximal expiratory pressure; after follow-up this group also had a lower incidence of pneumonia. CONCLUSIONS: The addition of percussive ventilation to the usual chest physiotherapy regimen in tracheostomized patients improves gas exchange and expiratory muscle performance and reduces the incidence of pneumonia.