[Multicenter study of rhDNase in cystic fibrosis with severe pulmonary involvement]

Pulmonary disease accounts for all the severity of cystic fibrosis. Impairment of forced vital capacity (FVC) under 40% of its predicted value is observed in about 7% of our patients and reflects a very advanced disease. For these patients, currently available treatments are inadequate and they are candidates for pulmonary transplantation, emphasizing the need for alternative treatments. We performed a randomized, double-blind, placebo-controlled, multicentric study to evaluate the safety and efficacy of aerosolised rhDNase 2.5 mg twice daily in patients with cystic fibrosis and severe impairment of pulmonary function. The first three aerosolisations were performed in the hospital, after bronchial drainage. Seventy patients, aged 5 to 48 years, were treated for 2 weeks. Respiratory parameters improved in both groups during the study period. As compared to baseline values, FVC improved by 13.7% and 12.7%, forced expiratory volume in one second (FEV1) by 6% and 7%, respectively in the placebo and rhDNase groups. No significant difference was detected between the two groups. However, after the completion of the randomized study, all patients received rhDNase as part of an open-label phase for 6 months. FEV1 and FVC further improved in all patients. We failed to demonstrate for severely ill patients with cystic fibrosis a significant advantage for aerosolised rhDNase compared to placebo for two weeks. The further improvement observed in the open-label phase suggests that more prolonged treatment might be necessary to detect a statistically significant benefit. No significant side effects of the treatment were observed.