Underestimation of lung clearance index values in infants with cystic fibrosis due to software analysis algorithms

Lung clearance index (LCI) is a marker of ventilation inhomogeneity and is usually elevated in children with cystic fibrosis (CF). However, often LCI values are found normal in infants with CF, although structural lung abnormalities are already detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. Thus, our aim was to challenge the validity of these software algorithms. We analyzed multiple breath washout (MBW) measurements from 17 asymptomatic infants with CF, and 17 healthy matched term-born infants. We compared current software algorithms (automatic modus) with refined software algorithms (manual modus). The main difference between these two analysis methods is based on the calculation of the molar mass differences that the system uses to define the completion of the measurement. In infants with CF the refined manual modus revealed elevated LCI above 9 in 8 out of 35 measurements (23%) that all showed normal LCI values using the automatic modus (paired t-test, p