Novel capnographic indices estimate ventilation inhomogeneity similarly to Lung Clearance Index

Background: The lung clearance index (LCI) obtained by multiple-breath washout (MBW) is a sensitive measure of ventilation inhomogeneity in children with cystic fibrosis (CF). However, MBW is time consuming and requires specialized equipment. The objective of this study was to evaluate novel capnographic inhomogeneity indices (CIIs) in children with CF. Methods: LCI and CIIs were calculated from N2-MBW data (including CO2 signal) from 33 children with CF (age 11.9 ± 4.3 years) and 13 healthy controls (10.9 ± 4.3). CIIs were calculated as the relative difference (%) in CO2 concentration at end-expiration between a)deadspace and alveolar compartment (CII1), b)deadspace and expired alveolar air (CII2) and, c)deadspace and alveolar air that initially washes-out the conductive airways (CII3). Results: LCI was higher in CF children compared to controls (10.3 ± 2.6 vs 6.8 ± 0.5, p<0.001). CIIs were also higher in CF patients (CII1 7.5 ± 2.0% vs 4.2 ± 1.0%, p<0.001; CII2 9.5 ± 2.4% vs 5.6 ± 1.2%, p<0.001; and CII3 12.1 ± 3.6% vs 6.5 ± 1.5%, p<0.001). Their ability to differentiate between CF and controls was excellent (AUC: CII1 0.937, CII2 0.932, CII3 0.942), and comparable to LCI (AUC 0.946). CIIs were strongly correlated to LCI (r = 0.749 to 0.763, p<0.001). The coefficient of variation was 3.9 ± 2.5 for CII1, 3.4 ± 2.3 for CII2 and 4.5 ± 2.3 for CII3, also comparable to LCI (3.0 ± 1.9%). Conclusions: Novel capnographic indices were as sensitive as LCI to detect ventilation inhomogeneity in children with CF. As these indices can be calculated through tidal breathing of room air, they potentially provide a simpler, faster, and less expensive method to assess ventilation distribution than MBW.