Sensitive structural and functional measurements and 1-year pulmonary outcomes in pediatric cystic fibrosis

•LCI2.5, 129Xe VDP, and UTE more sensitive to pediatric CF disease than spirometry.•1H MRI suggests increased odds for airway damage in lobes with mucus plugging.•Most spirometry measures correlated with consolidations and ground glass.•LCI2.5 and 129Xe VDP correlated with mucus plugging.•Increased exacerbations most strongly correlated with mucus plugs and airway damage. Two functional measurements (multiple breath washout [MBW] and hyperpolarized 129Xe ventilation magnetic resonance imaging [129Xe MRI]) have been shown to be more sensitive to cystic fibrosis (CF) lung obstruction than traditional spirometry. However, functional techniques may be sensitive to different underlying structural abnormalities. The purpose of this study was to determine relationships between these functional markers, their pathophysiology, and 1-year clinical outcomes. Spirometry, MBW, 129Xe MRI, and ultrashort echo-time (UTE) MRI were obtained in a same-day assessment of 27 pediatric CF patients (ages 11.5±5.0) who had not begun CFTR modulator therapies. UTE MRI was scored for structural abnormalities and functional metrics obtained via spirometry, MBW and 129Xe MRI. 1-year outcomes (ΔFEV1 and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record. MBW, 129Xe MRI, and UTE MRI detected clinically significant disease in more subjects (>78%) compared to spirometry (