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Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians

Sanja Stanojevic, Brian L. Graham, Brendan G. Cooper, Bruce R. Thompson, Kim W. Carter, Richard W. Francis, Graham L. Hall on behalf of the Global Lung Function Initiative TLCO working group
European Respiratory Journal 2017 50: 1700010; DOI: 10.1183/13993003.00010-2017
Sanja Stanojevic
1Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
2Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada
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  • For correspondence: Sanja.Stanojevic@sickkids.ca
Brian L. Graham
3Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon, SK, Canada
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Brendan G. Cooper
4Lung Function and Sleep, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Bruce R. Thompson
5Allergy Immunology and Respiratory Medicine, The Alfred Hospital and Monash University, Melbourne, Australia
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Kim W. Carter
6Bioinformatics, Telethon Kids Institute, Perth, Australia
7Centre for Child Health Research, University of Western Australia, Perth, Australia
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Richard W. Francis
6Bioinformatics, Telethon Kids Institute, Perth, Australia
7Centre for Child Health Research, University of Western Australia, Perth, Australia
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  • ORCID record for Richard W. Francis
Graham L. Hall
7Centre for Child Health Research, University of Western Australia, Perth, Australia
8Children's Lung Health, Telethon Kids Institute, Perth, Australia
9School of Physiotherapy and Exercise Science, Curtin University, Perth, Australia
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  • Article
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Figures

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  • Supplementary Materials
  • FIGURE 1
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    FIGURE 1

    a) Predicted transfer factor of the lung for carbon monoxide (TLCO) in i) males n=4859 and ii) females n=4851; b) alveolar volume (VA) (at standard temperature, pressure and dry conditions) in i) males n=4793 and ii) females n=4837; and c) transfer coefficient of the lung for carbon monoxide (KCO) in i) males n=4793 and ii) females n=4837. Data are presented as the predicted values for age (assuming an average height at each) and 95% confidence limits. Prediction equations are overlaid on observed values. The average height used in children was the 50th height-for-age centile from Centers for Disease Control and Prevention growth charts [4], whereas in adults, the average height observed in the study population was used (172 cm in males and 162 cm in females).

  • FIGURE 2
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    FIGURE 2

    Between-subject variability of transfer factor of the lung for carbon monoxide (TLCO) across age; the variability of forced expiratory volume in 1 s (FEV1) in males and females is included as a comparator.

  • FIGURE 3
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    FIGURE 3

    Differences in a) transfer factor of the lung for carbon monoxide (TLCO) in i) males n=4859 and ii) females n=4851; b) alveolar volume (VA) in i) males n=4793 and ii) females n=4837; and c) transfer coefficient of the lung for carbon monoxide (KCO) z-scores in i) males n=4793 and ii) females n=4837 according to equipment in Caucasian subjects. Boxplots indicate the median value (centre line); interquartile range (box) and minimum and maximum values, excluding outliers greater than three times the lower quartile (error bars).

  • FIGURE 4
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    FIGURE 4

    Comparison of transfer factor of the lung for carbon monoxide (TLCO) reference equations to the current Global Lung Function Initiative (GLI) equations. Equations found in a) most commercially available equipment and b) more recently published studies.

Tables

  • Figures
  • Supplementary Materials
  • TABLE 1

    Summary of Caucasian data included in the Global Lung Function Initiative transfer factor of the lung for carbon monoxide reference values

    CountrySubjectsEquipmentAltitude mAnatomic VDBreath-hold calculationReported valuesCaucasian %Obese %FEV1 z-score
    New Zealand71SensorMedics Vmax Encore20FixedJones–MeadeAverage10018.30−0.31±0.9
    Australia605Other8FixedJones–MeadeAverage10018.400.56±1.0
    Australia120SensorMedics Vmax Encore10FixedJones–MeadeAverage1008.300.25±0.9
    Spain430Jaeger MasterScreen710Body size adjustedJones–MeadeAverage10027.90−1.0±1.3
    The Netherlands543Jaeger MasterScreen13FixedUnknownAutomated1003.00NR
    USA300SensorMedics Vmax Encore222Body size adjustedJones–MeadeAverage1009.000.03±0.9
    USA1302Collins50Body size adjustedJones–MeadeAutomated10018.100.14±0.9
    Bulgaria547Jaeger MasterScreen150Body size adjustedJones–MeadeLargest1008.000.3±0.8
    Bulgaria335Jaeger MasterScreen150Body size adjustedJones–MeadeLargest10010.20NR
    Mexico191Other2240FixedJones–MeadeAverage10014.100.04±1.2
    Greece942Jaeger MasterScreen460FixedUnknownLargest10027.600.3±0.9
    New Zealand151SensorMedics Vmax Encore10FixedJones–MeadeAverage1004.60−0.5±1.0
    Italy80Other100UnknownUnknownUnknown100NR0.06±0.9
    Italy3552SensorMedics Vmax Encore904UnknownUnknownAverage10025.700.2±1.0
    Canada541OtherVariousUnknownUnknownUnknown1007.800.4±1.6

    Data are presented as n or mean±sd, unless otherwise stated. VD: dead space volume; FEV1: forced expiratory volume in 1 s; NR: not reported.

    • TABLE 2

      The corrected equations for predicted values for the median (M), the variability around the median (S) and the skewness (L) for each of the TLCO test outcomes (transfer factor of the lung for carbon monoxide (TLCO), transfer coefficient of the lung for carbon monoxide (KCO) and alveolar volume (VA))

      MSL
      Male
      TLCO mmol·min-1·kPa-1exp(-8.129189 + 2.018368·ln(height) - 0.012425·ln(age) + Mspline)exp(-1.98996 + 0.03536·ln (age) + Sspline)0.39482
      DLCO mL·min-1·mmHg-1exp(-7.034920 + 2.018368·ln(height) - 0.012425·ln(age) + Mspline)
       
      KCO (SI) mmol·min-1·kPa-1·L-1exp(2.994137 - 0.415334·ln(height) - 0.113166·ln(age) + Mspline)exp(-1.98186 + 0.01460·ln(age) + Sspline)0.67330
      KCO (trad) mL·min-1·mmHg-1·L-1exp(4.088408 - 0.415334·ln(height) - 0.113166·ln(age) + Mspline)
       
      VA Lexp(-11.086573 + 2.430021·ln(height) + 0.097047·ln(age) + Mspline)exp(-2.20953 + 0.01937·ln(age) + Sspline)0.62559
       
      Female
      TLCO mmol·min-1·kPa-1exp(-6.253720 + 1.618697·ln(height) - 0.015390·ln(age) + Mspline)exp(-1.82905 - 0.01815·ln(age) + Sspline)0.24160
      DLCO mL·min-1·mmHg-1exp(-5.159451 + 1.618697·ln(height) - 0.015390·ln(age) + Mspline)
       
      KCO (SI) mmol·min-1·kPa-1·L-1exp(4.037222 - 0.645656·ln(height) - 0.097395·ln(age) + Mspline)exp(-1.63787 - 0.07757·ln(age) + Sspline)0.48963
      KCO (trad) mL·min-1·mmHg-1·L-1exp(5.131492 - 0.645656·ln(height) - 0.097395·ln(age) + Mspline)
       
      VA Lexp(-9.873970 + 2.182316·ln(height) + 0.082868·ln(age) + Mspline)exp(-2.08839 - 0.01334·ln(age) + Sspline)0.51919

      Mspline, Sspline correspond to the age-varying coefficients from the look-up tables provided in the supplementary material. Height and age are expressed as cm and years, respectively. Predicted value: M; lower limit of normal (5th percentile): exp(ln(M) + ln(1 - 1.645·L·S)/L); upper limit of normal (5th percentile): exp(ln(M) + ln(1 + 1.645·L·S)/L); z-score: ((measured/M)L - 1)/(L·S); % predicted: (measured/M)·100; exp: natural exponential; ln: natural logarithm. This table has been amended in the article originally published in the September 2017 issue of the European Respiratory Journal.

      • TABLE 3

        Comparison of predicted values for individuals using available transfer factor of the lung for carbon monoxide (TLCO) reference values

        First author, year [reference]TLCO mmol·min−1·kPa−1
        178-cm, 64-year-old male178-cm, 20-year-old male150-cm, 10-year-old male
        GLI, 20179.210.96.4
        Crapo, 1981 [16]11.314.5
        Miller, 1983 [19]9.212.6
        Roca, 1990 [17]10.313.3
        Gutierrez, 2004 [28]8.310.5
        Thompson, 2008 [26]9.310.8
        Koopman, 2011 [22]6.4
        Kim, 2012 [23]6.0

        The list of equations is not meant to be comprehensive, rather it provides a range of differences that might be expected. GLI: Global Lung Function Initiative.

        • TABLE 4

          Summary of the practical recommendations for applying Global Lung Function Initiative transfer factor of the lung for carbon monoxide (TLCO) reference values

          Barometric pressure (altitude)TLCO and KCO values should be adjusted to standard pressure (101.3 kPa or 760 mmHg) prior to calculation of predicted values
          Anatomic dead spaceAnatomic dead space should be either measured from the tracer gas washout or estimated using body size
          HbTLCO values should be uncorrected for Hb; Hb levels should be considered in the interpretation

          Hb: haemoglobin; KCO: transfer coefficient of the lung for carbon monoxide.

          Supplementary Materials

          • Figures
          • Tables
          • Supplementary Material

            Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

            Supplementary material ERJ-00010-2017_Supplement

            Lookup table (S.I. units); this supplementary file has been republished in an amended form subsequent to the correction article published in the October 2020 issue of the European Respiratory Journal ERJ-00010-2017_Lookup_Table_SI_Units

            Lookup table (traditional units); this supplementary file has been republished in an amended form subsequent to the correction article published in the October 2020 issue of the European Respiratory Journal ERJ-00010-2017_Lookup_Table_Traditional_Units

            TLCO calculator ERJ-00010-2017_TLCO_Calculator

            TLCO calculator help document ERJ-00010-2017_TLCO_Calculator_Help

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          Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians
          Sanja Stanojevic, Brian L. Graham, Brendan G. Cooper, Bruce R. Thompson, Kim W. Carter, Richard W. Francis, Graham L. Hall
          European Respiratory Journal Sep 2017, 50 (3) 1700010; DOI: 10.1183/13993003.00010-2017

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          Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians
          Sanja Stanojevic, Brian L. Graham, Brendan G. Cooper, Bruce R. Thompson, Kim W. Carter, Richard W. Francis, Graham L. Hall
          European Respiratory Journal Sep 2017, 50 (3) 1700010; DOI: 10.1183/13993003.00010-2017
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