Longitudinal assessment of Lung Clearance Index as a marker of disease progression in a cohort of children with cystic fibrosis and normal spirometry

Abstract

Objectives: The lung clearance index at 2.5 of starting concentration (LCI2.5) from Nitrogen multiple breath washout (MBW) has demonstrated sensitivity to early lung disease in Cystic Fibrosis (CF). Our study aims to evaluate if the LCI2.5 can identify lung disease progression in children with CF with normal lung function by spirometry.

Methods: We have enrolled 57 children with CF (mean age 10.3 + 3, range 6 - 18 years; 22 boys, 35 girls) into a longitudinal study that evaluates spirometry, MBW and patient reported outcomes at clinical encounters. Our main endpoint is FEV1 decline over one year.

Results: At baseline these children demonstrated normal parameters (mean FVC 99.2 + 20 %-pred., FEV1 94 + 21 %-pred., FEV1/FVC ratio 0.84 + 0.12; BMI 61 + 24 %-ile), with no significant differences between boys and girls (p > 0.25 for all). However, by LCI there was evidence for airway disease (Mean 9.4 units + 2.6) and with no differences between boys and girls (p = 0.5).

At baseline modest correlation was found between LCI and FEV1%-pred. (r 0.45, p = 0.001). During follow up, on average no significant change in FEV1 was noted (p = 0.57). However, there was an inverse correlation between baseline LCI and FEV1 decline (-2.5 %-pred./year for every unit of LCI2.5, p= 0.0001) and between change in LCI2.5 and FEV1 decline (-2.0 %-pred./year for every unit of increase in LCI2.5, p < 0.0001).

Conclusion: The LCI2.5 from MBW identifies children with subsequent decline in FEV1. One unit increase in LCI seems to be a strong indicator of lung disease activity.

Funding Source: US CFF MILLA17A0