Exhaled breath compositions under varying respiratory rhythms reflects ventilatory variations: translating breathomics towards respiratory medicine

Figures

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  Figure 1. Relative changes in normalised mean alveolar concentrations of selected substances and respiratory parameters from 25 healthy subjects during administration of different respiratory rhythms: Setup-1 (top); Setup-2 (bottom). VOCs were tentatively identified based on their m/z. Respiratory rhythms were changed every 3 min. VOC data (from both setups) were normalised on to corresponding values in the second exhalation of setup-1. Respiratory parameters were normalised in the same way. VTex = expiratory tidal volume, pET-CO2 = end-tidal partial pressure of carbon dioxide, V′E = minute ventilation, FIO2 = fraction of inspiratory oxygen, V’CO2 = carbon dioxide production, V’O2 = oxygen consumption. For VOCs, changes in colours from red to blue symbolise relative changes from higher to lower concentrations and vice versa. Similarly, for respiratory parameters, changes in colours from light grey to black represent relative changes from higher to lower values and vice versa.

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  Figure 2. Continuous breath-resolved changes in normalised mean alveolar concentrations of endogenous isoprene and acetone along with minute ventilation and pET-CO2 from all participants in both setups. X-axis represents measurement time in both setups. Y-axis represents normalised (on to corresponding values in the second exhalation of setup-1 for each subject) mean values of measured parameters. Respiratory rhythms were changed every 3 min and such time points are divided via red lines.

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  Figure 3. Comparison of differences in intra-individual variations of respiratory parameters, -isoprene and acetone within both setups. X-axis represents spontaneous respiratory rhythms from both setups. Y-axis represents mean values of relative standard deviations (i.e. RSDs in %) of measured parameters. RSDs over 180 s of all rhythms were compared to each other. Comparisons were also performed over final 60 s (steady state) of each rhythm. V’E and pET-CO2 values were compared in the same way. Statistical significances were tested by means of repeated measurement-ANOVA on ranks (p-value ≤ 0.005). From all pairwise-multiple comparisons, statistically indifferent (i.e. with no significant differences and thereby, reproducible) respiratory rhythms are marked with red-coloured ovals.

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  Figure 4. Comparisons of exhaled alveolar concentrations and corresponding inter-individual variations of endogenous isoprene, -acetone and respiratory parameters. X-axis represents two study setups with three respiratory rhythms in each. Y-axis represents normalised mean (_norm.Mean) values and inter-individual variations (_iivs.) of measured parameters, respectively. Exhaled VOC concentrations and intra-individual variations from same respiratory rhythm (over 180 s) were compared within- and between two setups. V’E and pET-CO2 values were compared in the same way. Statistical significances were tested by means of repeated measurement-ANOVA on ranks (p-value ≤ 0.005). From all pairwise-multiple comparisons, statistically indifferent (i.e. with no significant differences and thereby, reproducible) rhythms are marked with red-coloured ‘ ≅ ’ for respiratory phases.

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  Figure 5. Comparison of differences in exhaled alveolar concentrations of endogenous isoprene, -acetone and respiratory parameters during spontaneous breathing in both setups. X-axis represents spontaneous respiratory rhythms from both setups. Y-axis represents normalised mean (_norm.Mean) values of measured parameters, respectively. Exhaled VOC concentrations from spontaneous rhythms were compared. Comparisons were performed over 60 s (presented on reader’s left) and over 30 s (presented on reader’s right) of intervals. V’E and pET-CO2 values were compared in the same way. Statistical significances were tested by means of repeated measurement-ANOVA on ranks (p-value ≤ 0.005). From all pairwise-multiple comparisons, statistically indifferent (i.e. with no significant differences and thereby, reproducible) spontaneous breathing intervals are marked with red-coloured ‘≈’.

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  Figure 6. Regression models [Eqs. (1) and (2)] from Setup-1 are predicting breath-resolved ventilatory variations: Equations are presented along with corresponding prediction scores and residual plots. Predicted [by Eqs. (1) and (2)] and actually observed ventilatory variations in Setup-2: Measured data from setup-2 were applied onto Eqs. (1) and (2) in order to predict breath-resolved variations in V’E and pET-CO2, respectively. X-axis represents breath numbers. Y-axis represents actually observed values and predicted values of breath-resolved variations in V’E and pET-CO2. The Kolmogorov–Smirnov test showed excellent agreement between the independently predicted ventilatory variations in setup-2 and the actual measures.

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  Figure 7. A scheme of study setup-1 and setup-2. This indicates the switching of respiratory rhythms over time along with all analytical and clinical instrumentations.