Structural lung disease in preschool children with cystic fibrosis: An 18 month natural history study

Background: This study was performed to describe the natural history of CF lung disease in young children over an 18 month period to assess the use of CT scanning as an outcome measure for intervention trials.

Methods: Chest CT scans were obtained at baseline and after 18 months in 42 two- to six-year-old children with CF. CT scans were scored by 2 experienced radiologists for the presence and severity of bronchiectasis, mucous plugging, and air trapping.

Results: Mean age at baseline 3.5 (1.3) (mean, sd) years. One or more findings of CF lung disease was seen on the first CT in 27 (64%) and at 18 months in 30 (75%). From baseline to 18 months bronchiectasis, mucous plugging, and air trapping increased from 50% to 53%, 14% to 28%, and 48% to 58% respectively. There was marked variability in the rate of progression, with subjects commonly showing improvement in lung disease. Bronchiectasis worsened in 14 (33%) and improved in 13 (31%). Single subjects with F508del/class III and F508del/class V demonstrated greater worsening and improvement respectively than F508del homozygous and class I genotypes.

Conclusions: The natural history of CF lung disease over 18 months varies widely between subjects. Factors including genotype may affect natural history as well as the effectiveness of mediators and could be an important confounder if not recognized. These findings suggest that the use of CT scanning as an outcome surrogate for CF lung disease in young children may be more challenging than has been previously recognized.