Chest
Volume 128, Issue 4, October 2005, Pages 2327-2335
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Clinical Investigations
Dornase Alfa Reduces Air Trapping in Children With Mild Cystic Fibrosis Lung Disease: A Quantitative Analysis

https://doi.org/10.1378/chest.128.4.2327Get rights and content

Purpose

To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest.

Materials and methods

Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF25–75%); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images.

Results

At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF25–75%, and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF25–75% and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (− 15.4%) and worsened in the placebo group (+ 61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment.

Conclusions

Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.

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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    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.

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