Introduction 

Multiple breath washout (MBW) and HRCT scans are sensitive and complementary methods for monitoring cystic fibrosis (CF) lung disease in all age groups.

Aim

To explore changes on structural lung disease and lung function in infants and toddlers with CF (itwCF) and the effect of CFTR-modulator therapy on these.

Methods
Serial lateral decubitus position CTs and sedated SF₆MBWs were performed as part of monitoring in itwCF diagnosed by newborn screening for CF. Primary endpoints were CT derived PRAGMA-CF defined percentage of bronchiectasis (%BE) and MBW derived z-score of ventilation distribution efficiency (z-VDE). Descriptive statistics and mixed model analyses were employed.

Results
CT and MBW were performed in 25 itwCF aged median (range) 1.85 years (0.2; 4.3) providing 49 CTs (11 children with 1, 4 with 2 and 10 with 3) and 144 MBWs (2-11 each). BE was observed in 39 (80%) of scans, and abnormal z-VDE < -1.65 in 89 (62%) of MBWs. Median (range) of %BE and z-VDE were 0.3 (0.0; 3.9) and -2.03 (-7.10; 1.26) respectively. Serial CTs showed progressing of %BE in 10 of the children. Progression was likewise demonstrated on z-VDE in 7 of the 10 (70%) children.

The mean (95%CI) annual changes were 95.5% (32.9; 187.5) p=0.002 and -0.49 (-0.84; -0.15) p=0.007, respectively. The progression in %BE and z-VDE during the first years of life was ameliorated after modulator therapy with luma/ivacaftor, ?%BE: -65,3% [-86.7; -9.3] p=0.034 and ?zVDE: +1.68 (0.64; 2.72) p=0.002.

Conclusions
Both CT and MBW reveal progression of CF lung disease in the first years of life. Beneficial effects of CFTR-modulator can be demonstrated using either CT scans or MBW but appear to provide complementary information.