Longitudinal Monitoring of Lumacaftor/Ivacaftor Response in Young Children with Cystic Fibrosis Lung Disease Using 129Xe MRI.

RATIONALE AND

OBJECTIVES

Hyperpolarized 129Xe magnetic resonance imaging (MRI) can sensitively detect subtle abnormalities in subjects with pulmonary disease. In this work, we assess lung disease progression and treatment response to Lumacaftor/Ivacaftor in patients with cystic fibrosis.

METHODS

18 cystic fibrosis (CF) patients underwent a longitudinal study: nine subjects (8.7±2.4years, 3M/6F) initiated lumacaftor/ivacaftor therapy (48±51days post-Visit 1), and 9 (15.3±4.3years, 5M/4F) served as controls. Spirometry, multiple breath washout (Lung Clearance Index, LCI2.5), and 129Xe MRI were acquired at baseline, short-term (6±3months), and long-term (15±4months) follow-ups. Changes in spirometry measurements, LCI, ventilation defect percentage (VDP), and defect distribution index (DDI) assessed by 129Xe MRI, were compared between groups using non-parametric tests.

RESULTS

The control group was significantly older (P=0.0028) and trended toward higher initial VDP (14.7±8.1% vs 6.9±6.0%) and DDI (14.4±24.7 vs 4.7±4.3). Baseline spirometry and LCI showed no differences between groups. In the treatment group, VDP and DDI remained stable after treatment (ΔVDP12= -0.56±2.1%, ΔDDI12= 1.1±4.0) but the change was significantly lower than in controls (ΔVDP12= 2.75±2.82%, P=0.018; DDI12= 8.88±7.42, P=0.007). From Visit-2 to Visit-3, VDP increased significantly in the treatment group (ΔVDP23 = 3.33±2.79%, P=0.025) versus controls (ΔVDP23= -1.7±4.8%). No significant changes occurred in spirometry or LCI.

CONCLUSION

129Xe MRI demonstrated high sensitivity in detecting functional changes between pediatric CF patients on and off modulator therapy. In the short term, 129Xe ventilation measures remained stable with modulator therapy and demonstrated declines in the 2 years following. These findings highlight 129Xe MRI's potential as a valuable clinical tool for monitoring lung function and disease progression, even with small cohorts of patients.