Prospective longitudinal association between repeated multiple breath washout measurements and computed tomography scores in children with cystic fibrosis

Background: Progression of structural lung disease (SLD) is a major risk factor for morbidity in patients with cystic fibrosis (CF). We studied changes in SLD and correlations with spirometry and nitrogen multiple breath washout (N ₂MBW) outcomes to explore associations in contemporary evolution between structural and functional abnormalities in CF lung disease. Methods: Spirometry-controlled chest-CTs using PRAGMA-CF for scoring extent of SLD, spirometry, and N ₂MBW were performed at two-year intervals in school-age children with CF. Results: Fifty-seven children aged 6–18 years were included. No significant progression in mean PRAGMA-CF scores was observed. Half of the children showed improvement in the proportion of bronchiectasis (%Bx). Lung Clearance Index (LCI) and the second moment ratio (M2) increased significantly and baseline values correlated significantly with SLD at follow-up (p ≤ 0.0002). The correlation between the change in M2 (∆M2) and the change in total SLD was R = 0.27 (p = 0.048). We found high negative predictive values (100%) for ∆M2<10% to exclude progression in SLD. For stable or improving values of LCI and M2, the predicted probability for progression in SLD was 16% and 14%, respectively (upper 95% confidence limit: 33%). Evolution in N ₂MBW and CT outcomes was discordant in half of the children. Conclusions: We found no progression in SLD over 2 years in school-age children with CF, in contrast to both LCI and M2, which along with discordant outcomes in half of the children underlines that N ₂MBW and CT assess different aspects of CF lung disease. However, stable outcomes from N ₂MBW were associated with stable structural lung disease.