RESUMO
OBJECTIVE: Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations. STUDY DESIGN: This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor. RESULTS: Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar. CONCLUSIONS: Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.
Assuntos
Fibrose Cística/tratamento farmacológico , Desoxirribonuclease I/uso terapêutico , Expectorantes/uso terapêutico , Pneumopatias/congênito , Pneumopatias/tratamento farmacológico , Pulmão/anormalidades , Proteínas Recombinantes/uso terapêutico , Fatores Etários , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Criança , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Desoxirribonuclease I/administração & dosagem , Método Duplo-Cego , Expectorantes/administração & dosagem , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pneumopatias/etiologia , Masculino , Proteínas Recombinantes/administração & dosagem , Testes de Função Respiratória , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
To establish the symptoms and clinical course of juvenile-onset mixed connective tissue disease, we studied 14 patients, classified according the criteria of Kasukawa et al. The patient records were studied retrospectively and all patients were examined in a 1-day follow-up program. Systemic lupus erythematosus and polymyositis/dermatomyositis-like symptoms disappeared in time, whereas scleroderma-like symptoms (such as in the Raynaud phenomenon) and joint abnormalities persisted. Extensive limitation of joint function was found in four patients. At the time of follow-up, no active renal disease was found. Thrombocytopenia was still present in one of the three patients who had had this feature. All patients had abnormalities of esophageal motility. Long-term corticosteroid treatment was associated with aseptic bone necrosis in three patients and growth retardation in one. We conclude that the Kasukawa criteria are easy to apply to children, and that juvenile-onset mixed connective tissue disease has many similarities to the adult form of the disease.