Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease: a quantitative analysis.
OBJECTIVE
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.


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 (FEF(25-75%)); 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 FEF(25-75%), 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 FEF(25-75%) 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.
Robinson
Terry E
TE
Department of Pediatrics (Pulmonary), Pediatric Pulmonary Division, Stanford University Medical Center, 701 Welch Rd, Whelan Building, #3328, Palo Alto, CA 94305-5786, USA. ter@stanford.edu
Goris
Michael L
ML
Zhu
Hongyun J
HJ
Chen
Xiaorong
X
Bhise
Prache
P
Sheikh
Farzana
F
Moss
Richard B
RB
D000388:Air / Q000032:analysis*; D002648:Child; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D010919:Placebos; D012129:Respiratory Function Tests; D014057:Tomography, X-Ray Computed
D010919:Placebos; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I