EFFICACY AND SAFETY OF SHORT-TERM ADMINISTRATION OF AEROSOLIZED RECOMBINANT HUMAN DEOXYRIBONUCLEASE IN PATIENTS WITH CYSTIC-FIBROSIS

Chronic endobronchial bacterial infection evokes purulent airway secre tions in patients with CF The viscoelastic properties of these secreti ons is primarily due to the presence of polymerized DNA from degenerat ing leukocytes. Recombinant human DNase I (rhDNase) reduces the viscos ity of CF sputum in vitro. To test the hypothesis that rhDNase would i mprove pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aer osolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expi ratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) acro ss all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0. 001). rhDNase was associated with a decreased perception of dyspnea an d an improved perception of well-being. No patients developed detectab le anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some pa tients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNas e to pediatric and adult outpatients with CF improves lung function an d is well tolerated. Although all three doses were efficacious, the gr eatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.