Chest
Clinical InvestigationsDornase Alfa Reduces Air Trapping in Children With Mild Cystic Fibrosis Lung Disease: A Quantitative Analysis
Section snippets
Study Design
We conducted a randomized, double-blind, placebo-controlled, 1-year trial of dornase alfa in 25 children and adolescents with mild CF lung disease. All children had a confirmed diagnosis of CF by pilocarpine iontophoresis sweat chloride test and/or CF gene mutation analysis. Inclusion criteria included routine medical care in a CF clinic, age 6 to 18 years, percentage of predicted FVC ≥ 85% and a percentage of predicted FEV1 approximately ≥ 70%, and the ability to perform reproducible PFTs.
Results
Twenty-five CF subjects were enrolled and randomized, and 21 subjects completed the 1-year trial with follow-up testing. All four noncompleters withdrew for nonstudy drug-related reasons. For the quantitative air trapping analysis, 25 subjects could be evaluated at baseline and 3 months; however, only 19 subjects (3 fewer subjects from each group) could be evaluated at baseline and 12 months due to noncompleters and the unavailability of stored electronic imaging for postprocessed CT image
Discussion
In this 1-year intervention study evaluating the effect of dornase alfa in children with mild CF lung disease, only the visual mucus plugging CT score at 1 year demonstrated significant differences between groups, with a continued decline in the dornase alfa group compared to an increase in the placebo group. However, this discrimination only occurred at 1 year and not at 3 months. Overall, much more consistent differences between groups at 3 months and 12 months were demonstrated in the
ACKNOWLEDGMENT
The authors thank Tyson Holmes from the Division of Biostatistics, Health Research and Policy, Stanford University Medical Center, for statistical analysis; Malayattil Vijayalakshmi, Anne S. Bonnel, Krishnaveni and Kesavaraju for technical support; and Glenn Hodge (Pediatric Pulmonary Function Laboratory) and Lisa McClennan and Diane Holmes (Pediatric Radiology Section- Ultrafast CT imaging) for their participation in the study.
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Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis
2021, Journal of Cystic FibrosisCitation Excerpt :More generally, the observed influence of dornase alfa on FEV1 and FEF25–75 is supported by several previous studies in both children and adults with CF as summarised in a recent systematic review [14]. However, randomised, controlled trials restricted to school-age children with mild to moderate CF lung disease have demonstrated mixed treatment effects of dornase alfa on spirometric parameters [9,24,25]. A large study by Quan et al. [24] reported significant improvements in FEV1, whereas two smaller studies did not [9,25].
Fenretinide favorably affects mucins (MUC5AC/MUC5B) and fatty acid imbalance in a manner mimicking CFTR-induced correction
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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).
Dr. Robinson received a research grant from Genentech, Inc. of $3,700.00 representing the cost of pharmacist set-up and inventory activities associated with Pulmozyme and placebo medication for this study.
Dr. Moss has received research grants from Genentech, Inc. for studies related to Pulmozyme since 1993.
This study was funded by the Cystic Fibrosis Foundation and Genentech, Inc.