4.2.4 Validity
The discriminatory ability of LCI holds after correction with a linear
trend to lower LCI values for healthy but also children with CF.
Thereby, the higher the LCI value, the higher the downward correction,
which needs closer reevaluation of patients with highly elevated LCI.
Potentially, the overestimation of back-diffusion of N2might have overrated LCI values of patients with more severe disease and
longer washouts. However, correlation with functional defects detected
by MRI scans 17,18,20 remained very similar before and
after measurement correction, reassuring that the pathophysiological
understanding of LCI is still valid. Correspondingly, the pattern of
increase in LCI with age remained similar with a smaller magnitude after
measurement correction (Figure 3, Supplemental Figure 4). A very similar
effect was seen by Robinson et al. reanalyzing change in LCI in
preschool CF children over 12 months 2. In line with
Robinson et al., treatment effects of CFTR modulators remained
statistically significant whereas the magnitude of the change was
smaller.