Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis

Background Volumetric capnography (VCap) is a simpler alternative to multiple-breath washout (MBW) to detect ventilation inhomogeneity in patients with cystic fibrosis (CF). However, its diagnostic performance is influenced by breathing dynamics. We introduce two novel VCap indices, the capnographic inhomogeneity indices (CIIs), that may overcome this limitation and explore their diagnostic characteristics in a cohort of CF patients. Methods We analysed 320 N-2-MBW trials from 50 CF patients and 65 controls (age 4-18 years) and calculated classical VCap indices, such as slope III (SIII) and the capnographic index (KPIv). We introduced novel CIIs based on a theoretical lung model and assessed their diagnostic performance compared to classical VCap indices and the lung clearance index (LCI). Results Both CIIs were significantly higher in CF patients compared with controls (mean +/- SD CII1 5.9 +/- 1.4% versus 5.1 +/- 1.0%, p=0.002; CII2 7.7 +/- 1.8% versus 6.8 +/- 1.4%, p=0.002) and presented strong correlation with LCI (CII1 r(2)=0.47 and CII2 r(2)=0.44 in CF patients). Classical VCap indices showed inferior discriminative ability (SIII 2.3 +/- 1.0%/L versus 1.9 +/- 0.7%/L, p=0.013; KPIv 3.9 +/- 1.3% versus 3.511.2%, p=0.071), while the correlation with LCI was weak (SIII r(2)=0.03; KPIv r(2)=0.08 in CF patients). Clis showed lower intra-subject inter-trial variability, calculated as coefficient of variation for three and relative difference for two trials, than classical VCap indices, but higher than LCI (CII1 11.1 +/- 8.2% and CIT2 11.0 +/- 8.0% versus SIII 16.3 +/- 13.5%; KPIv 15.9 +/- 12.8%; LCI 5.9%14.2%). Conclusion CIIs detect ventilation inhomogeneity better than classical VCap indices and correlate well with LCI. However, further studies on their diagnostic performance and clinical utility are required.