Search

Objective. Although dornase alfa is a widely used, aerosolized, mucolytic agent in patients with cystic fibrosis (CF), its efficacy in relation to the timing of physiotherapy has not been tested. We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure (PEP) therapy in clinically stable children.Methods. Using a crossover, randomized, double-blind, and placebo-controlled trial, we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home. There were 2 treatment orders. Dornase alfa before + placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks. The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks. The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second (FEV[1]), a composite quality of well-being score (QWB), and a measure of aerobic fitness (maximal oxygen consumption, [VO[2max]), determined using shuttle testing.Results. Fifty-two patients who had CF (27 female) with mild to moderate suppurative lung disease, were a mean +/- SD age of 10.7 +/- 3.2 years, had Shwachman scores of 86 +/- 11.8, had predicted FEV[1] of 83% +/- 18%, had quality of well-being score of 0.76 +/- 0.08, and had VO[2max] of 42.6 +/- 6.3 ml/kg per min were enrolled. Fifty patients completed the study. Intention-to-treat analysis was used. Nonsignificant mean (95% confidence interval) differences in FEV[1] (0.02 L [-0.05 to 0.10]), VO[2max] (-0.75 ml/kg per min [-1.85 to 0.35]), and QWB (0.005 [-0.94 to 0.0028]) for dornase alfa after physiotherapy/PEP were detected. A post hoc analysis showed that patients who were colonized persistently with Pseudomonas aeruginosa had a significantly greater improvement in FEV[1] (0.12 L [0.23 to 0.01] vs-0.04 L [0.05 to-0.13]) when dornase alfa was administered after physiotherapy/PEP.Conclusions. Dornase alfa is equally efficacious when delivered before or after physiotherapy/PEP in patients with CF. Patients who are colonized persistently with P aeruginosa may derive more improvement in FEV[1] when dornase alfa is delivered after physiotherapy/PEP. [ABSTRACT FROM AUTHOR]

Objective: To determine whether infants with hyaline membrane disease (HMD) superimposed on immature lung disease (ILD) have more abnormal lung function and respiratory drive during the evolution of chronic neonatal lung disease (CNLD) in extremely low birth weight infants (ELBW; <1000 g)., Methods: We measured lung mechanics (respiratory frequency, tidal volume, minute ventilation, lung resistance, lung compliance, lung impedance, and work of breathing per minute) and respiratory drive (airway opening pressure 100 milliseconds after initiation of breath [P(0.1)] and maximal inspiratory pressure generated during airway occlusion) on 3 occasions before term in 24 ELBW infants., Results: Ten infants with ILD (mean [95% CI] gestation: 24.3 weeks [23.1,25.4]; birth weight: 675 g [553,798]) were studied at 27, 31, and 35 weeks of postconceptional age and 14 infants with HMD superimposed on ILD (gestation: 25.1 weeks [24.4,25.9]; birth weight: 687 g [601,773]) were studied at 28, 32, and 35 weeks of postconceptional age. There were no statistically significant differences between the groups for respiratory frequency, tidal volume, minute ventilation, lung resistance, lung compliance, lung impedance, work of breathing per minute, P(0.1), and maximal inspiratory pressure generated during airway occlusion. With increasing age, both groups demonstrated increased respiratory drive as measured by P(0.1) without significant changes in respiratory frequency or CO(2). Work of breathing per minute increased in the HMD group with age and was higher in extubated subjects. A similar trend with age was demonstrated in ILD infants. Regardless of whether the initial lung disease was ILD alone or HMD + ILD, ELBW infants developed a mildly reduced lung compliance/kg (.8-1.1 mL/cm.H(2)O/kg) and high lung resistance (75-125 cm.H(2)O/L/second) pattern of CNLD, which changed little after 3 weeks of age. Survival to 6 months was 23/24 (96%). Oxygen dependency was 16/24 (67%) at 35 weeks, yet only 5/23 (22%) survivors required oxygen at discharge from the neonatal unit (43 weeks)., Conclusions: The visco-elastic and flow-resistive properties of the lungs in ELBW infants with CNLD remain only mildly abnormal, suggesting a more favorable prognosis for lung function in later years than previously reported.