c) longitudinal tracking
To assess the differences in the longitudinal course of LCI between
Spiroware 3.2.1 and 3.3.1, we reanalyzed 796 measurements from 72
children with CF (Table 1). Without adjustment for risk factors, LCI
increase was comparable in both settings, however less pronounced in
Spiroware 3.3.1 (0.16 LCI units/year (95% CI 0.08; 0.24) vs. 0.30 LCI
units/year (95% CI 0.21; 0.38) in Spiroware 3.2.1). The pattern of
increase in LCI was similar in both settings, remaining stable during
preschool years and school-age and then starting to increase in
adolescence (Figure 3 and Supplemental Table 2). Similar to our previous
findings, Aspergillus and P. aeruginosa colonization, severe
exacerbations, and experiencing ABPA during the study period remained
individually associated with a steeper increase in LCI also in Spiroware
3.3.1, even though with a smaller magnitude (Supplemental Table 3). The
effect on covariates associated with acute changes in LCI (acute
exacerbations, CF-related diabetes, BMI z-score) remained similar for
both Spiroware settings (Supplemental Table 4). With adjustment for
previously defined risk factors (sex, BMI, PsA- and
Aspergillus-colonization, CF-related diabetes, acute and severe
exacerbations) the pattern of increase in LCI was similar for both
Spiroware settings, again, less pronounced for 3.3.1 (0.08 LCI
units/year (95% CI 0.01; 0.14) (Spiroware 3.3.1) vs. 0.19 LCI
units/year (95% CI 0.12; 0.27) in Spiroware 3.2.1) (Supplemental Figure
4).
d) Response to intervention To characterize differences in the response to intervention with double
or triple modulator therapy between Spiroware 3.2.1 and 3.3.1, we
reanalyzed 212 visits from 28 patients (Table 1) and compared mean LCI
values at baseline, under double, under triple, and combined therapy.
There was a statistically significant improvement (reduction) in LCI in
all three treatment groups when compared to baseline in both Spiroware
algorithms (Figure 4). In Spiroware 3.2.1, within-group mean (95% CI)
absolute change from baseline was -1.7 LCI units (-2.8 to -0.5, p=0.012)
under double therapy, -1.7 LCI units (-2.5 to -0.9; p≤0.001) under
triple therapy, and -2.5 LCI units (-4.1 to -1.0; p=0.007) under
combined modulator therapy (Figure 4 and supplemental Table 5). In
Spiroware 3.3.1, LCI was substantially lower but the change from
baseline remained statistically significant in all groups (within-group
mean (95% CI) absolute change from baseline was -1.5 LCI units (-2.5 to
-0.4, p=0.013) under double therapy, -1.3 LCI units (-1.9 to -0.7;
p≤0.001) under triple therapy, and -1.7 LCI units (-2.9 to -0.5;
p=0.014) under combined modulator therapy). Overall, within-group mean
values differed substantially between Spiroware 3.2.1 and 3.3.1 (mean
(95% CI) difference between software versions over all groups was -1.5
(-2.0 to -1.1) LCI units).
Discussion