Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis

The aim of the study was to measure the effect of a short course of recombi nant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2. 5 mg qd) or placebo. Following the measurement of baseline clearance, patie nts were given a 7-day course of either rhDNase or placebo. The patient the n returned on the seventh day for follow-up clearance measurements. This wa s followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucoc iliary clearance was initially measured for a period of 60 min (IC). This w as followed by cough clearance (CC) measurements for 30 min, during which p atients were requested to cough a total of 120 times. Post-cough clearance (PCC) was then measured for a further 60 min. Thirteen patients completed the study. Patients' age ranged between 18-38 y ears, and they had baseline values of FEV, of 27-103% of predicted values. Following completion of the course of rhDNase, there was a mean percent inc rease from baseline of 7.5% for FEV1 and 5.4% for FVC% (P = 0.03). There wa s a small, nonsignificant increase in IC (6.2 +/- 3.6%) on the rhDNase arm compared with the placebo arm (-2.3 +/- 2.9016), P = 0.1. No changes were s een in either CC (1.0 +/- 3.2% [rhDNase] vs. 1.9 +/- 2.4% [placebo], P = 0. 9) or PCC (-0.7 +/- 1.5% [rhDNase] vs. 0.9 +/- 1.7% [placebo], P = 0.3). Pa tients who achieved a 10% or greater improvement in FEV, (n = 5) in respons e to rhDNase did not show any greater change in clearance than nonresponder s. In conclusion, we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase. The me chanism of action of this drug in vivo remains uncertain. (C) 2000 Wiley-Li ss, Inc.