Early Determinants Of Lung Disease In Children With Cystic Fibrosis

Background: Lung Clearance Index (LCI) is a sensitive measure of lung disease in children with cystic fibrosis (CF). The aim of this study was to determine whether there are modifiable factors that affect the course of lung disease during childhood. Methods: In this prospective two centre cohort study, we continued to follow a cohort (Stanojevic et al., AJRRCM 2017) of children with CF and age-matched healthy controls (HC) into school age (5-10 years). LCI was measured every 3 months for 24 months using Exhalyzer® D multiple breath nitrogen washout equipment. Detailed clinical data were extracted at each study visit, and for the years between the two follow-up periods. Mixed effects linear regression analyses were used. Results: In total 76% of the original preschool cohort (50/72 HC and 64/78 CF) were followed-up at school age. A total of 607 LCI measurements (HC) and 832 measurements (CF) were available for analysis. At the first school age visit, LCI was 2.15 units higher in the CF group compared to the controls (95%CI -2.68; 1.62); LCI was above 7.91 units (68.8%) in 40 children, of which 54% had abnormal LCI during the preschool period. A higher preschool LCI, faster rate of LCI deterioration during preschool years and a greater cumulative number of exacerbations were significant predictors of worse school age LCI. During the school age follow-up, LCI plateaued (slope = 0.07 (95% -0.1; 0.2) with age. Overall, a greater proportion of children received mucolytics and/or modulator treatments during the school age years compared with the preschool years. Conclusions: Early intervention before or during preschool are a critical time period to prevent future lung function impairment. Funded by NHLBI, CFF