PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis

Am J Respir Crit Care Med. 2015 May 15;191(10):1158-65. doi: 10.1164/rccm.201501-0061OC.


Rationale: Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airway disease. However, there are no standardized outcome measures appropriate for children younger than 6 years.

Objectives: We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airway disease, and compared it with 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 10 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 30 paired scans obtained at 1 and 3 years old were used for comparison with a validated standard and biologic 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 presence at age 3, whereas only the change in bronchiectasis score was related to neutrophil elastase (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.

Keywords: clinical trials as topic; medical imaging; pediatrics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchiectasis / diagnostic imaging*
  • Bronchiectasis / pathology
  • Bronchiectasis / physiopathology
  • Child, Preschool
  • Clinical Trials as Topic / methods
  • Cystic Fibrosis / diagnostic imaging*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / physiopathology
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Lung / diagnostic imaging*
  • Lung / pathology
  • Lung / physiopathology
  • Male
  • Observer Variation
  • Reproducibility of Results
  • Severity of Illness Index
  • Tomography, X-Ray Computed / methods*
  • Western Australia