Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis.
Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary function and reduces the rate of pulmonary exacerbations in cystic fibrosis subjects. Standard jet nebulizers are relatively inefficient and require a delivery time of 10-20 min. We conducted an open-label, proof-of-concept study to evaluate whether bolus inhalation of rhDNase with a more efficient delivery system was safe and effective in cystic fibrosis subjects. The AERx system used for this study aerosolized 1.35 mg of rhDNase in three inhalations at a single sitting. The predicted AERx lung dose was approximately 0.68 mg, a dose consistent with lung doses of rhDNase given by jet nebulizer. In our 16 subjects with cystic fibrosis, a mean relative increase in FEV(1) of 7.8% (p < or = 0.001) was observed after 15 days of bolus delivery of rhDNase with the AERx system. The safety profile of rhDNase given as a bolus was similar to that observed with traditional nebulizer delivery. This study demonstrated that bolus inhalation of rhDNase was feasible, reasonably well-tolerated, and associated with improvement in pulmonary function in this small group of cystic fibrosis subjects.
Geller
David
D
The Nemours Children's Clinic, Orlando, Florida 32806, USA. dgeller@nemours.org
Thipphawong
John
J
Otulana
Babatunde
B
Caplan
Daniel
D
Ericson
Dawn
D
Milgram
Laura
L
Okikawa
Jerry
J
Quan
Joanne
J
Bowman
C Michael
CM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000336:Aerosols; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I