title: Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis.
abstract: 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.
authors.affiliation: The Nemours Children's Clinic, Orlando, Florida 32806, USA. dgeller@nemours.org
authors.forename: David
authors.initials: D
authors.lastname: Geller
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
authors.forename: Babatunde
authors.initials: B
authors.lastname: Otulana
authors.forename: Daniel
authors.initials: D
authors.lastname: Caplan
authors.forename: Dawn
authors.initials: D
authors.lastname: Ericson
authors.forename: Laura
authors.initials: L
authors.lastname: Milgram
authors.forename: Jerry
authors.initials: J
authors.lastname: Okikawa
authors.forename: Joanne
authors.initials: J
authors.lastname: Quan
authors.forename: C Michael
authors.initials: CM
authors.lastname: Bowman
mesh_terms: 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
chemical_list: D000336:Aerosols; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I