Composite spirometric-computed tomography outcome measure in early cystic fibrosis lung disease.
With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.
Pediatric Pulmonary Division, Stanford University Medical Center, 701 Welch Road, Whelan Building #3328, Palo Alto, CA 94304-5786. ter@stanford.edu
Terry E
TE
Robinson
Ann N
AN
Leung
William H
WH
Northway
Francis G
FG
Blankenberg
Frandics P
FP
Chan
Daniel A
DA
Bloch
Tyson H
TH
Holmes
Richard B
RB
Moss
D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology*; D003850:Deoxyribonuclease I / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D015203:Reproducibility of Results; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013147:Spirometry; D013997:Time Factors; D014057:Tomography, X-Ray Computed
C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I