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.