A double-blind, randomized, double dummy, cross over, study
to assess the difference in efficacy between nebulisation of rhDNase before airway clearande therapy (ACT)versus nebulisation after ACT.

Introduction:
Though the effectiveness of rhDNase is well established, little research has been carried out to determine the optimal time relation between rhDNase and ACT.

Objective:
To assess the difference in lung function between nebulisation of rhDNase before ACT versus nebulisation after ACT.

Methods:
The study was a randomized, double blind, double dummy, cross over design. Inclusion criteria were CF, stable clinical condition and rhDNase maintenance therapy.
Randomisation:
- Group I: Week 1-3, inhalation of rhDNase 30 minutes before, and placebo directly after ACT. The reversed protocol was performed during week 4-6.
- Group II: Reversed sequence. Patients continued their daily routine ACT.
Primary endpoint:
MEF25. Flow volume manoeuvre and Rinte were measured on day 0, 14, 21, 35 and 42. The children scored cough and sputum production daily on diary cards in week 3 and 6.

Inhalation of rhDNase after airway clearande therapy (ACT) increases the expiratory flow at 25% of the actual forced vital capacity (MEF25) compared to inhalation of rhDNase before ACT.

N/A

The study was a randomized, double blind, double dummy, cross over design. All subjects nebulized daily both rhDNase (2.5 mg of rhDNase in 2.5 ml buffered solution:
8.77 mg/ml sodium chloride and 0.15 mg/ml calcium chloride)
and a placebo (2.5 ml of a buffered solution:
8.77 mg/ml sodium chloride and 0.15 mg/ml calcium chloride) once daily for a period of six weeks.
Placebo was similar to rhDNase in both color and taste.
Subjects were randomized to two groups.
Group I used rhDNase 30 minutes before ACT and placebo directly after ACT in the first three weeks. In the following three weeks rhDNase and placebo were taken in reversed order. (Figure 1)
Group II used placebo 30 minutes before ACT and rhDNase after ACT in the first three weeks. In the following three weeks placebo and rhDNase were taken in reversed order. Patients were asked to carry out their daily routine ACT and not to change their routine technique. The timing during the day of nebulisation and ACT were kept constant throughout the study.