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Simultaneous sulfur hexafluoride and nitrogen multiple-breath washout (MBW) to examine inherent differences in MBW outcomes

Katie J. Bayfield, Alex Horsley, Eric Alton, Samantha Irving, Andrew Bush, Jane C. Davies
ERJ Open Research 2019 5: 00234-2018; DOI: 10.1183/23120541.00234-2018
Katie J. Bayfield
1Imperial College London, London, UK
2Royal Brompton and Harefield NHS Foundation Trust, London, UK
3European Cystic Fibrosis Society Clinical Trials Network, Lung Clearance Index Core Facility, London, UK
4The Children's Hospital at Westmead, Sydney, Australia
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  • ORCID record for Katie J. Bayfield
  • For correspondence: katie.bayfield@health.nsw.gov.au
Alex Horsley
5Institute of Inflammation and repair, Education and Research centre, University of Manchester, University Hospital of South Manchester, Manchester, UK
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Eric Alton
1Imperial College London, London, UK
2Royal Brompton and Harefield NHS Foundation Trust, London, UK
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Samantha Irving
1Imperial College London, London, UK
2Royal Brompton and Harefield NHS Foundation Trust, London, UK
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Andrew Bush
1Imperial College London, London, UK
2Royal Brompton and Harefield NHS Foundation Trust, London, UK
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Jane C. Davies
1Imperial College London, London, UK
2Royal Brompton and Harefield NHS Foundation Trust, London, UK
3European Cystic Fibrosis Society Clinical Trials Network, Lung Clearance Index Core Facility, London, UK
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  • FIGURE 1
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    FIGURE 1

    Flow diagram of overall study design, including each section, devices used and participants. MBW: multiple-breath washout; CF: cystic fibrosis; HC: healthy control; RMS: respiratory mass spectrometer.

  • FIGURE 2
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    FIGURE 2

    Flowmeters of the Exhalyzer D (nitrogen; black box) and Innocor (sulfur hexafluoride; white box) were attached in series with airtight plastic tubing. After calibrating each device with this set-up, the gas concentration and breath number during a multiple-breath washout test were then measured simultaneously. In some cases, a respiratory mass spectrometer (RMS) gas probe was also placed between the other devices (grey dot) to read gas concentrations directly using the RMS.

  • FIGURE 3
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    FIGURE 3

    Bland–Altman plot of the difference in lung clearance index taken from the traditional end-point of 1/40th of the starting concentration (LCI2.5) between Exhalyzer D (nitrogen (N2ExD)) and Innocor (sulfur hexafluoride (SF6Inn)) in a) participants with cystic fibrosis (CF) and b) healthy control (HC) participants. The solid line is the mean difference between devices (4.5 in CF and 0.92 in HC) and the dotted lines represent the limits of agreement (0.08–8.92 in CF and −0.38–2.22 in HC). The difference between devices becomes disproportionately larger with a higher (worse) LCI.

  • FIGURE 4
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    FIGURE 4

    Bland–Altman plots of the difference in lung clearance index (LCI) taken from the 1/20th end-point of the starting concentration (LCI5) between Exhalyzer D (nitrogen (N2ExD)) ExD) and Innocor (sulfur hexafluoride (SF6Inn)) in a) participants with cystic fibrosis (CF) and b) healthy control (HC) participants. The solid line is the mean difference between devices (1.0 in CF and 0.01 in HC) and the dotted lines represent the limits of agreement (−0.48–2.49 in CF and −0.59–0.62 in HC). The difference between devices becomes disproportionately larger with a higher (worse) LCI. The difference in LCI5 is not as large as the difference in LCI2.5.

  • FIGURE 5
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    FIGURE 5

    Graph of an individual cystic fibrosis patient's gas concentration decline throughout a simultaneous washout of sulphur hexafluoride and nitrogen versus breath number. The gases are displayed in a normalised log scale for ease of visualisation. The vertical lines (dashed: SF6; solid: N2) represent the end-tidal gas concentration at 1/40th of the starting concentration; beyond this point is the extended washout period.

Tables

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  • TABLE 1

    Comparison of multiple-breath washout devices, cystic fibrosis (CF) and healthy control (HC) demographics and lung clearance index (LCI) results

    CF (n=47)HC (n=42)
    Female24 (51%)26 (62%)
    Age years16.05 (5.9–63.7)24.32 (5.7–56.1)
    Height cm, Z-score154.6±52.2, −0.07±1.1158.4±17.9, −0.79±1.1
    Weight kg, Z-score52.2±18, 0.60±1.159.7±20.6, −0.27±1.2
    FEV1 % pred, Z-score72.9±16.8, −2.29±1.43Not done
    SF6InnN2ExDDifference p-valueSF6InnN2ExDDifference p-value
    LCI2.59.5±2.3 (8.82 to 10.19)14.0±3.7 (12.88 to 15.14)−4.5 (−5.2 to −3.8), p=<0.00016.3±0.5 (6.12–6.5)7.3±0.72 (7.03–7.48)−0.9 (−1.1 to −0.7), p<0.0001
    LCI56.8±1.4 (6.38 to 7.23)7.9±1.7 (7.31 to 8.32)−1.01 (−1.2 to −0.8), p<0.00015.1±0.4 (4.97 to 5.20)5.1±0.3 (5.01 to 5.20)−0.02 (−0.12 to 0.08), p=0.709
    FRC2.5 L1.9±0.6 (1.73 to 2.09)2.5±0.9 (2.23 to 2.78)−0.6 (−0.7 to −0.5), p<0.00012.3±0.8 (2.05–2.55)2.5±0.9 (2.25–2.84)−0.2 (−0.3 to −0.2), p<0.0001
    CEV L18.4±7.7 (16.1–20.8)38.5±18.7 (33.9–44.2)−20.1 (−23.9 to −16.3), p<0.000114.5±5.6 (12.8–16.2)19.8±7.9 (17.4–22.3)−5.3 (−6.4 to −4.2), p<0.0001
    SF6InnMean LCI difference 3.2±0.4 (2.5 to 3.9) p<0.0001
    N2ExDMean LCI difference 6.8±0.6 (3.6 to 7.9) p<0.0001

    Results show mean±sd or median (range) with 95% confidence intervals for LCI2.6 and functional residual capacity (FRC). FEV1: forced expiratory volume in 1 s; HC: healthy control; LCI: lung clearance index; LCI2.5: lung clearance index calculated from washout to 1/40th of the tracer gas starting concentration; LCI5: lung clearance index calculated from washout to 1/20th of the tracer gas starting concentration; FRC: Functional Residual Capacity; CEV: Cumulative Expiratory Volume; MBW: multiple-breath washout; N2ExD: Exhalyzer D nitrogen device; SF6Inn: modified Innocor sulfur hexafluoride device.

    Supplementary Materials

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      Supplementary material 00234-2018.supplement

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    Simultaneous sulfur hexafluoride and nitrogen multiple-breath washout (MBW) to examine inherent differences in MBW outcomes
    Katie J. Bayfield, Alex Horsley, Eric Alton, Samantha Irving, Andrew Bush, Jane C. Davies
    ERJ Open Research Oct 2019, 5 (4) 00234-2018; DOI: 10.1183/23120541.00234-2018

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    Simultaneous sulfur hexafluoride and nitrogen multiple-breath washout (MBW) to examine inherent differences in MBW outcomes
    Katie J. Bayfield, Alex Horsley, Eric Alton, Samantha Irving, Andrew Bush, Jane C. Davies
    ERJ Open Research Oct 2019, 5 (4) 00234-2018; DOI: 10.1183/23120541.00234-2018
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