Lung structural and functional impairments in young children with cystic fibrosis diagnosed following newborn screening - A nationwide observational study

Abstract

Background: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV₁, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening.

Methods: Lung function (LCI, FEV₁) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood.

Results: LCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV₁ was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV₁. Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV₁ in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes.

Conclusions: The LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood.

Keywords: Children; Cystic fibrosis; Lung clearance index; Magnetic resonance imaging; Multiple breath washout.