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Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults

Thomas Radtke, Quintin de Groot, Sarah R. Haile, Marion Maggi, Connie C.W. Hsia, Holger Dressel
ERJ Open Research 2021 7: 00193-2021; DOI: 10.1183/23120541.00193-2021
Thomas Radtke
1Division of Occupational and Environmental Medicine, Epidemiology, Biostatistics and Prevention Institute, University of Zurich & University Hospital Zurich, Zurich, Switzerland
5These authors contributed equally
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  • ORCID record for Thomas Radtke
  • For correspondence: thomas.radtke@uzh.ch
Quintin de Groot
1Division of Occupational and Environmental Medicine, Epidemiology, Biostatistics and Prevention Institute, University of Zurich & University Hospital Zurich, Zurich, Switzerland
2Zurich University of Applied Sciences, School of Health Professions, Institute of Physiotherapy, Winterthur, Switzerland
5These authors contributed equally
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Sarah R. Haile
3Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
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Marion Maggi
1Division of Occupational and Environmental Medicine, Epidemiology, Biostatistics and Prevention Institute, University of Zurich & University Hospital Zurich, Zurich, Switzerland
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Connie C.W. Hsia
4Dept of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Holger Dressel
1Division of Occupational and Environmental Medicine, Epidemiology, Biostatistics and Prevention Institute, University of Zurich & University Hospital Zurich, Zurich, Switzerland
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  • FIGURE 1
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    FIGURE 1

    CONSORT flow chart.

  • FIGURE 2
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    FIGURE 2

    Comparison of mean individual raw data for diffusing capacity of the lung for nitric oxide (DLNO), diffusing capacity of the lung for carbon monoxide (DLCO), alveolar volume (VA), and permeability factor for NO (κNO) and permeability factor for CO (κCO) between MasterScreen and HypAir in 35 subjects measured sequentially in random order (HypAir-MasterScreen (HA-MS) or MasterScreen-HypAir (MS-HA)).

Tables

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  • TABLE 1

    Participant characteristics stratified by test period

    VariablesMasterScreen-HypAirHypAir-MasterScreenOverall
    Participants, n (%)22 (63)13 (37)35 (100)
    Sex, n (%)
     Male11 (50)6 (46)17 (49)
     Female11 (50)7 (54)18 (51)
    Age years40.8±2.938.8±5.240.0±15.5
    Height cm175.5±2.5172.8±2.7174.5±10.1
    Weight kg73.2±11.363.5±12.169.6 ±12.4
    BMI kg·m−223.7±2.721.1±2.222.7±2.8
    Heart rate beats·min−171.6±11.268.5±10.970.5±11.0
    SpO2 %97.7±0.997.3±1.297.5±1.0
    FEV1 MasterScreen z-score−0.01±0.91−0.38±0.63−0.15±0.82
    FVC MasterScreen z-score0.55±0.92−0.02±0.610.34±0.85
    FEV1 HypAir z-score0.20±0.92−0.22±0.700.04±0.86
    FVC HypAir z-score0.64±0.870.11±0.590.44±0.81

    Data are presented as mean±sd, unless otherwise stated. BMI: body mass index; SpO2: oxygen saturation measured by pulse oximetry; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity.

    • TABLE 2

      Descriptive analysis of primary and secondary end-points between MasterScreen and HypAir

      VariablesMasterScreenHypAirPer cent difference
      Primary end-point
        DLNO mL·min−1·mmHg−1121.30 (110.13 to 132.48)145.73 (132.04 to 159.41)−16.5 (−17.8 to −15.1)
      Secondary end-points
       DLCO mL·min−1·mmHg−128.47 (25.81 to 31.13)28.15 (25.46 to 30.84)1.4 (−0.1 to 2.9)
       Alveolar volume L5.80 (5.38 to 6.21)6.28 (5.85 to 6.71)−8.0 (−8.9 to – 7.0)
       Breath-hold time s6.28 (6.17 to 6.39)5.93 (5.81 to 6.05)6.2 (4.6 to 7.8)
       Inspiratory volume L4.66 (4.28 to 5.04)4.68 (4.31 to 5.05)−0.5 (−1.7 to 0.7)
       κNO s−1−6.13 (−6.25 to −6.00)−7.23 (−7.44 to −7.02)−14.6 (−17.3 to −11.9)
       κCO s−1−0.018 (−0.019 to −0.018)−0.022 (−0.022 to −0.021)−15.8 (−17.2 to −14.4)
       KNO mL·min−1·mmHg−1·L−120.8 (19.7 to 21.9)23.1 (21.8 to 24.4)−9.3 (−10.4 to −8.1)
       KCO mL·min−1·mmHg−1·L−14.9 (4.6 to 5.1)4.5 (4.2 to 4.7)10.2 (8.6 to 11.9)
       ΔFANO ppm−38.3 (−38.9 to −37.7)−42.8 (−44.1 to −41.5)−9.4 (−12.8 to −6.0)
       ΔFACO %−0.11 (−0.12 to −0.11)−0.13 (−0.13 to −0.13)−10.9 (−12.4 to −9.4)
       NO, expired/inspired ratio0.117 (0.107 to 0.127)0.100 (0.090 to 0.110)19.2 (13.9 to 24.6)
       O2, expired/inspired ratio0.877 (0.870 to 0.884)0.887 (0.873 to 0.900)−1.4 (−2.7 to −0.01)
       CO, expired/inspired ratio0.470 (0.458 to 0.481)0.475 (0.464 to 0.468)1.3 (−0.2 to 2.8)
       He, expired/inspired ratio0.737 (0.718 to 0.756)0.683 (0.665 to 0.702)−10.1 (−10.9 to −9.3)

      Data are presented as mean (95% CI). DLCO: diffusing capacity of the lung for CO; DLNO: diffusing capacity of the lung for NO; κCO: permeability factor for CO; κNO: permeability factor for NO; KNO: transfer coefficient of the lung for NO; KCO: transfer coefficient of the lung for CO; FACO: fractional concentration of CO in the alveolar space; FANO: fractional concentration of NO in the alveolar space; ΔFACO (expired–inspired CO concentration); ΔFANO (expired–inspired NO concentration). Ratios of expired to inspired gas concentrations are also shown.

      • TABLE 3

        Mixed linear models on differences in DLNO and secondary end-points between MasterScreen and HypAir devices

        VariablesCoefficient95% CIp-value
        Primary end-point
          DLNO mL·min−1·mmHg−124.021.7 to 26.3<0.0001
        Secondary end-points
         DLCO mL·min−1·mmHg−1−0.03−0.57 to 0.120.20
         Alveolar volume L0.480.45 to 0.52<0.0001
         Breath-hold time s−0.33−0.42 to −0.24<0.0001
         Inspiratory volume L0.008−0.028 to 0.0260.66
         κNO s−1−1.08−1.21 to −0.94<0.0001
         κCO s−1−0.0035−0.004 to −0.003<0.0001
         KNO mL·min−1·mmHg−1·L−12.21.9 to 2.5<0.0001
         KCO mL·min−1·mmHg−1·L−1−0.41−0.46 to −0.37<0.0001
         ΔFANO ppm−4.40−5.15 to −3.66<0.0001
         ΔFACO %−0.015−0.016 to −0.013<0.0001
         NO, expired/inspired ratio−0.017−0.012 to −0.014<0.0001
         O2, expired/inspired ratio0.0120.005 to 0.0190.0014
         CO, expired/inspired ratio−0.007−0.012 to −0.0020.0063
         He, expired/inspired ratio−0.054−0.058 to −0.050<0.0001

        Data are presented as mean (95% confidence interval). Positive coefficients means that HypAir gave larger measurements than MasterScreen. DLCO: diffusing capacity of the lung for CO; DLNO: diffusing capacity of the lung for NO; κCO: permeability factor for CO; κNO: permeability factor for NO; KNO: transfer coefficient of the lung for NO; KCO: transfer coefficient of the lung for CO; FACO: fractional concentration of CO from the alveolar space; FANO: fractional concentration of NO from the alveolar space; ΔFACO (expired–inspired CO concentration); ΔFANO (expired–inspired NO concentration). Ratios of expired to inspired gas concentrations are also shown.

        • TABLE 4

          Intrasession variability characteristics for MasterScreen and HypAir

          VariablesMasterScreenHypAir
          Measurement error#Repeatability¶CV %ICCMeasurement error#Repeatability¶CV %ICC
          DLNO mL·min−1·mmHg−16.7618.734.890.972 (0.952–0.985)5.9716.524.050.962 (0.934–0.979)
          DLCO mL·min−1·mmHg−11.163.223.800.986 (0.975–0.992)0.972.703.380.981 (0.968–0.990)
          VA L0.110.301.770.995 (0.992–0.997)0.110.311.790.993 (0.987–0.996)

          Data were measured at a target breath-hold time of 5 s. CV: coefficient of variation; ICC: intraclass correlation coefficient; DLNO: diffusing capacity of the lung for NO; DLCO: diffusing capacity of the lung for CO; VA: alveolar volume. #: the measurement error (or within-subject standard deviation, SDws) was calculated by the root mean square method; ¶: repeatability of gas diffusing measurements was calculated as the SDws from all three single-breath tests separately and multiplied by 2.77 (95% level of confidence).

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          Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults
          Thomas Radtke, Quintin de Groot, Sarah R. Haile, Marion Maggi, Connie C.W. Hsia, Holger Dressel
          ERJ Open Research Jul 2021, 7 (3) 00193-2021; DOI: 10.1183/23120541.00193-2021

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          Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults
          Thomas Radtke, Quintin de Groot, Sarah R. Haile, Marion Maggi, Connie C.W. Hsia, Holger Dressel
          ERJ Open Research Jul 2021, 7 (3) 00193-2021; DOI: 10.1183/23120541.00193-2021
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