title: Effect of rhDNase on airflow obstruction and mucociliary clearance in cystic fibrosis.
abstract: We tested the hypothesis that recombinant human deoxyribonuclease 1 (rhDNase) reduces airflow obstruction and improves mucociliary clearance in patients with cystic fibrosis (CF), and that improvements seen in FEV1 and FVC after rhDNase treatment are independent of chest physical therapy (CPT). CF patients inhaled placebo (10 patients) or 2.5 mg rhDNAse aerosol (10 patients) twice a day for six consecutive days. Compared with baseline, there were no statistically significant differences between the two study groups by Day 6 for indices of airflow obstruction obtained from gamma-camera images of the right lung following inhalation of 99mTc aerosol, or for mucociliary clearance or the rate of clearance of the radioaerosol, quantified over a 6-h period. By Day 6, FEV1 and FVC were significantly higher in the rhDNase-treated group than in the placebo group, increasing by an average of 9.4 +/- 3.5% and 12.7 +/- 2.6%, respectively, as compared with a decrease of 1.8 +/- 1.7% and an increase of 0.4 +/- 1.1%, respectively (p < 0.05). There was no significant change in the FEV1/FVC ratio on Day 6 (0.68 +/- 0.05) compared with baseline (0.70 +/- 0.05) in the rhDNase group. On Day 6, FEV1 and FVC decreased after CPT in both study groups, but the decreases were not significant. Our results indicate that aerosolized rhDNase improves FEV1 and FVC independent of CPT. We were unable to demonstrate that rhDNase reduces airflow obstruction or improves mucociliary clearance.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Laube
authors.forename: R M
authors.initials: RM
authors.lastname: Auci
authors.forename: D E
authors.initials: DE
authors.lastname: Shields
authors.forename: D H
authors.initials: DH
authors.lastname: Christiansen
authors.forename: M K
authors.initials: MK
authors.lastname: Lucas
authors.forename: H J
authors.initials: HJ
authors.lastname: Fuchs
authors.forename: B J
authors.initials: BJ
authors.lastname: Rosenstein
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D010316:Particle Size; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012138:Respiratory Therapy; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000336:Aerosols; D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I