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. 2022 Mar 14;8(1):00440-2021.
doi: 10.1183/23120541.00440-2021. eCollection 2022 Jan.

Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis

Sotirios Fouzas  1   2 , Anne-Christianne Kentgens  3   2 , Olga Lagiou  1 , Bettina Sarah Frauchiger  3 , Florian Wyler  3 , Ilias Theodorakopoulos  1 , Sophie Yammine  3 , Philipp Latzin  3
Affiliations

Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis

Sotirios Fouzas et al. ERJ Open Res. .

Abstract

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 N2-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 r2=0.47 and CII2 r2=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 3.5±1.2%, p=0.071), while the correlation with LCI was weak (SIII r2=0.03; KPIv r2=0.08 in CF patients). CIIs 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 CII2 11.0±8.0% versus SIII 16.3±13.5%; KPIv 15.9±12.8%; LCI 5.9%±4.2%).

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.

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Conflict of interest statement

Conflicts of interest: S. Fouzas has nothing to disclose. Conflicts of interest: A-C. Kentgens repots no other conflicts of interest. Conflicts of interest: O. Lagiou has nothing to disclose. Conflicts of interest: B.S. Frauchiger has nothing to disclose. Conflicts of interest: F. Wyler has nothing to disclose. Conflicts of interest: I. Theodorakopoulos has nothing to disclose. Conflicts of interest: S. Yammine repots no other conflicts of interest. Conflicts of interest: P. Latzin reports grants from Vertex and Vifor paid to his institution, personal fees and honoraria paid to his institution from Vertex, Vifor and OM Pharma, fees for participation on a data safety monitoring or advisory board from Santhera (DMC), and personal fees paid to his institution from Polyphor, Vertex, OM pharma and Vifor, all outside the submitted work. Support statement: The work was supported by Swiss National Science Foundation Grants (Yammine 179905 and Latzin 182719). A-C. Kentgens is a recipient of the Swiss Government Excellence Scholarship from The Swiss Confederation. Funding information for this article has been deposited with the Crossref Funder Registry.

Figures

FIGURE 1
FIGURE 1
The three-compartment model of our study and the respective volumetric capnograms. a) Without inhomogeneity (ideal lung); b) with sequential inhomogeneity. See text for complete description. VE: expiratory volume; VA: alveolar compartment volume; VD: dead space compartment volume; VECO2: expired CO2 volume; FECO2: mixed expired CO2 fraction; SIII: slope of phase III; FACO2: CO2 fraction in alveolar compartment; FDCO2: CO2 fraction in dead space compartment; FA1–3: alveolar sub-compartments.
FIGURE 2
FIGURE 2
VCap analysis with extension by VD. a) As originally proposed by Aitken and Clark-Kennedy [26]; b) as applied in our study. See text for detailed explanations. VE: expiratory volume; VD: dead space compartment volume; SIII: slope of phase III; VECO2: expired CO2 volume; VDCO2: CO2 volume in dead space compartment.
FIGURE 3
FIGURE 3
Boxplots showing the difference between patients with cystic fibrosis and healthy controls in mean values of a) CII1 and b) CII2, c) LCI, d) SIII and e) KPIv. The individual black dots represent mean values per subject. CII: capnographic inhomogeneity index; LCI: lung clearance index; SIII: slope of phase III; KPIv: capnographic index.
FIGURE 4
FIGURE 4
Relationship between a) SIII and VE, b) CII1 and SIII and c) CII2 and SIII in CF (green dots) and healthy control trials (black open dots). CF: cystic fibrosis; SIII: slope of phase III; VE: expiratory volume; CII: capnographic inhomogeneity index.
See this image and copyright information in PMC

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