TY - JOUR

T1 - PRAGMA-CF. A quantitative structural lung disease CT outcome in young children with cystic fibrosis

AU - Rosenow, Tim

AU - Oudraad, Merel C.J.

AU - Murray, Conor P.

AU - Turkovic, Lidija

AU - Kuo, Wieying

AU - de Bruijne, Marleen

AU - Ranganathan, Sarath C.

AU - Tiddens, Harm A.W.M.

AU - Stick, Stephen M.

PY - 2015

Y1 - 2015

N2 - RATIONALE: Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airways disease. However, there are no standardised outcome measures appropriate for children under 6 years.OBJECTIVES: We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airways disease, and compared it to the commonly used CF-CT scoring method.METHODS: CT scans from the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort in Western Australia were included. PRAGMA-CF was performed by annotating a grid overlaid on ten axial slices for the presence of bronchiectasis, mucous plugging or other airway abnormalities (inspiratory scans) and trapped air (expiratory scans). The separate proportions of total disease (%Dis), bronchiectasis (%Bx) and trapped air (%TA) were determined. Thirty scans were used for observer reliability, and thirty paired scans obtained at 1 and 3-years old were used for comparison with a validated standard and biological plausibility.MEASUREMENTS AND MAIN RESULTS: Intraobserver, intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx and %TA were 0.93 (0.86 - 0.97), 0.93 (0.85 - 0.96) and 0.96 (0.91 - 0.98), respectively. The change in %Dis (p = 0.004) and %Bx (p = 0.001) with PRAGMA-CF was related to neutrophil elastase (NE) presence at age 3, whereas only the change in bronchiectasis score was related to NE (p < 0.001) with CF-CT. Sample size calculations for various effect sizes are presented.CONCLUSIONS: PRAGMA-CF is a sensitive and reproducible outcome measure for assessing the extent of lung disease in very young children with CF.

AB - RATIONALE: Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airways disease. However, there are no standardised outcome measures appropriate for children under 6 years.OBJECTIVES: We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airways disease, and compared it to the commonly used CF-CT scoring method.METHODS: CT scans from the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort in Western Australia were included. PRAGMA-CF was performed by annotating a grid overlaid on ten axial slices for the presence of bronchiectasis, mucous plugging or other airway abnormalities (inspiratory scans) and trapped air (expiratory scans). The separate proportions of total disease (%Dis), bronchiectasis (%Bx) and trapped air (%TA) were determined. Thirty scans were used for observer reliability, and thirty paired scans obtained at 1 and 3-years old were used for comparison with a validated standard and biological plausibility.MEASUREMENTS AND MAIN RESULTS: Intraobserver, intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx and %TA were 0.93 (0.86 - 0.97), 0.93 (0.85 - 0.96) and 0.96 (0.91 - 0.98), respectively. The change in %Dis (p = 0.004) and %Bx (p = 0.001) with PRAGMA-CF was related to neutrophil elastase (NE) presence at age 3, whereas only the change in bronchiectasis score was related to NE (p < 0.001) with CF-CT. Sample size calculations for various effect sizes are presented.CONCLUSIONS: PRAGMA-CF is a sensitive and reproducible outcome measure for assessing the extent of lung disease in very young children with CF.

U2 - 10.1164/rccm.201501-0061OC

DO - 10.1164/rccm.201501-0061OC

M3 - Journal article

C2 - 25756857

VL - 191

SP - 1158

EP - 1165

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 10

ER -