Lung clearance index and functional MRI outcomes to assess lung disease in preschool children with cystic fibrosis

Abstract

Background: Lung disease starts early in life in children with cystic fibrosis (CF). Lung clearance index (LCI) and functional matrix-pencil magnetic resonance imaging (MP-MRI) are sensitive and non-invasive tools to monitor early lung disease.

Aim: Assess lung function outcomes (LCI; FEV₁ from spirometry) in preschool children with CF and healthy controls and their association with MP-MRI outcomes.

Methods: Children with CF from a nationwide newborn-screened cohort in Switzerland (SCILD) underwent lung function testing and MP-MRI at 4 and 6 years of age. MP-MRI outcomes included relative lung perfusion (R_Q) and ventilation (R_V) impairment as percentage of lung volume. Lung function outcomes at 6 years were compared to age-matched healthy controls.

Results: Twenty-one children were recruited at 4 years (mean (standard deviation) 4.2y (0.4)) and 41 children at 6 years (6.7y (0.6)) along with 44 healthy controls (6.2y (0.4)). Children with CF at 4 years had a mean LCI of 8.0 (1.3); 24% had an abnormal LCI (upper limit of normal: 8.0), and 14% an abnormal FEV₁ (z-score < -1.96). Children with CF at 6 years of age had a mean LCI of 8.0 (1.3), which was significantly higher than healthy controls (6.9 (0.7) p< 0.001), 39% had an abnormal LCI and 2% an abnormal FEV₁. MP-MRI outcomes in children with CF correlated with LCI (R_Q: r= 0.7, p<0.001; R_V: r= 0.63, p<0.001) but not FEV₁ (R_Q: r= -0.13, p=0.4; R_V: r=-0.15, p=0.3).

Conclusion: LCI and MP-MRI are superior to standard lung function testing in assessing early lung disease in children with CF. Functional MP-MRI allows visualization and quantification of ventilation and perfusion defects in CF lung disease.