Dornase alfa in early cystic fibrosis lung disease.
Leukocytes that infiltrate cystic fibrosis (CF) sputum as a result of infection have long been known to liberate large amounts of DNA, which increases sputum viscosity and promotes the cycle of chronic lung infection and inflammation that ultimately leads to respiratory failure and death. It was only recently recognized that this vicious cycle begins in infancy, and that architectural damage to CF lungs is detectable even in children with normal pulmonary function tests. Dornase alfa cleaves DNA and improves sputum viscosity in CF. Although its efficacy in reducing the risk of acute infectious exacerbations and improving pulmonary function has been recognized for a decade, there is growing interest in its potential for long-term benefit in young patients with mild lung function abnormalities. The Pulmozyme Early Intervention Trial (PEIT) study demonstrated that dornase alfa reduces the risk of pulmonary exacerbations requiring i.v. antibiotic treatment by 34% and improves forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), mid-expiratory flow at 50% of forced vital capacity (MEF), and forced expired volume in 1 sec (FEV(1)) over a 2-year period in CF patients with almost normal lung function. A post hoc subgroup analysis suggests that the magnitude of pulmonary function test (PFT) changes may vary, depending on the initial degree of lung function impairment, but that the reduction in exacerbations appears to be a consistent benefit. These results support the current view that CF patients benefit from intervention early in the course of their lung disease.
Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Australia.
Philip J
PJ
Robinson
D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004247:DNA / Q000032:analysis; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D006801:Humans; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013183:Sputum / Q000737:chemistry; D016896:Treatment Outcome; D014783:Viscosity
D011994:Recombinant Proteins; D004247:DNA; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I