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Standardisation of the single-breath determination of carbon monoxide uptake in the lung

N. MacIntyre, R. O. Crapo, G. Viegi, D. C. Johnson, C. P. M. van der Grinten, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, P. Enright, P. Gustafsson, J. Hankinson, R. Jensen, R. McKay, M. R. Miller, D. Navajas, O. F. Pedersen, R. Pellegrino, J. Wanger
European Respiratory Journal 2005 26: 720-735; DOI: 10.1183/09031936.05.00034905
N. MacIntyre
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R. O. Crapo
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G. Viegi
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D. C. Johnson
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C. P. M. van der Grinten
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V. Brusasco
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F. Burgos
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R. Casaburi
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A. Coates
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P. Enright
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P. Gustafsson
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J. Hankinson
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R. Jensen
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R. McKay
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M. R. Miller
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D. Navajas
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O. F. Pedersen
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R. Pellegrino
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J. Wanger
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  • Fig. 1—
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    Fig. 1—

    Schematic of lung volume (a) and gas concentrations (b) during the single-breath diffusing capacity of the lung for carbon monoxide. The gas-sampling period occurs between the two dotted lines. -----: tracer gas; – – –: carbon monoxide. #: dead space washout; ¶: sample collection. Modified from 1.

  • Fig. 2—
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    Fig. 2—

    Potential problems with the single-breath diffusing capacity of the lung for carbon monoxide breathing manoeuvre that can lead to measurement errors. ·······: stepwise inhalation or exhalation; – - –: exhaled gas leak; – -- –: inhalation too slow; – – –: exhaled volume larger than inhaled volume; ------: transient overshoot from high flows and changing gas temperatures. Adapted from 2.

  • Fig. 3—
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    Fig. 3—

    Schematic illustration of different methods of measuring breath-hold time for the single-breath diffusing capacity of the lung for carbon monoxide. The method by Ogilvie (––––––) 48 measures breath-hold time from the beginning of inspiration to the beginning of alveolar sample collection. The method by Jones and Meade (···········) 68 includes 0.70 of inspiratory time and half of sample time. The Epidemiologic Standardization Project (– – – –) measures breath-hold time from the time of 50% of inspired volume (VI) to the beginning of alveolar sample collection. tI: time of inspiration (-----; defined from the back-extrapolated time 0 to the time that 90% of the VI has been inhaled); TLC: total lung capacity; RV: residual volume. #: dead space washout; ¶: sample collection. Adapted from 1.

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Tables

  • Figures
  • Table. 1—

    Physiological and pathological changes that affect the carbon monoxide diffusing capacity of the lung(DL,CO)

    Extrapulmonary reduction in lung inflation (reduced VA) producing changes in DM or θVc that reduce DL,CO
     Reduced effort or respiratory muscle weakness
     Thoracic deformity preventing full inflation
    Diseases that reduce θVc and thus reduce DL,CO
     Anaemia
     Pulmonary emboli
    Other conditions that reduce θVc and thus reduce DL,CO
     Hb binding changes (e.g. HbCO, increased FI,O2)
     Valsalva manoeuvre (increased intrathoracic pressure)
    Diseases that reduce (in varying degrees) DM and θVc and thus reduce DL,CO
     Lung resection (however, compensatory recruitment of θVc also exists)
     Emphysema
     Interstitial lung disease (e.g. IPF, sarcoidosis)
     Pulmonary oedema
     Pulmonary vasculitis
     Pulmonary hypertension
    Diseases that increase θVc and thus increase DL,CO
     Polycythaemia
     Left-to-right shunt
     Pulmonary haemorrhage (not strictly an increase in θVc, but effectively an increase in lung Hb)
     Asthma
    Other conditions that increase θVc and thus increase DL,CO
     Hb binding changes (e.g. reduced FI,O2)
     Muller manoeuvre (decreased intrathoracic pressure as in asthma, resistance breathing)
     Exercise (in addition, a possible DM component)
     Supine position (in addition, possibly a slight increase in DM)
     Obesity (in addition, a possible DM component)
    • VA: alveolar volume; DM: membrane conductivity; θ: carbon monoxide (CO)–haemoglobin (Hb) chemical reaction rate; Vc: volume of pulmonary capillary blood; FI,O2: inspired fraction of oxygen; IPF: idiopathic pulmonary fibrosis; Hb: haemoglobin.

  • Table. 2—

    Equipment specifications

    Volume accuracyATS/ERS standards (currently 3.5% accuracy over an 8-L volume using test gases, with a testing syringe accuracy of 0.5%)
    Gas analysersLinear from zero to full span within ±0.5% of full span. Stable over the duration of the test with drift <±0.5% of a measured gas
    Circuit resistance<1.5 cmH2O·L−1·s−1 at a flow of 6 L·s−1
    Demand-valve sensitivity<10 cm H2O required for 6 L·s−1 flow through valve and circuit (if compressed gas source used)
    Timer±1.0% over 10 s (100 ms)
    Apparatus/valve filter VD<0.350 L
    • ATS: American Thoracic Society; ERS: European Respiratory Society; VD: dead space volume.

  • Table. 3—

    Equipment quality control

    Gas-analyser zeroingDone before/after each test
    Volume accuracyTested daily
    Standard subject or simulator testingTested at least weekly
    Gas-analyser linearityTested every 3 months
    TimerTested every 3 months
  • Table. 4—

    Inspired gas mixtures used during measurements of normal carbon monoxide(CO) uptake for commonly used reference equations

    Author [Ref.]Gas mixture#
    Teculescu 751.5% He, balance air (FI,O2 0.20)
    Van Ganse 7614–15% He, balance air (FI,O2 0.18)
    Frans 7710% He, 18% O2
    Crapo 7810% He, 25% O2 (comparable to 21% at sea level)
    Paoletti 7910% He, 20% O2
    Knudson 8010% He, 21% O2
    Roca 8113% He, 18% O2
    Huang 250.3% CH4, 0.3% C2H2, balance air (FI,O2 0.20)
    Miller 8210% He, ?balance air
    • He: helium; FI,O2: inspired oxygen fraction; CH4: methane; C2H2: acetylene. #: in addition to 0.3% CO.

  • Table. 5—

    Corrections for barometric pressure(PB), ambient water vapour pressure (PH2O), partial pressure of CO2 and temperature

    H2O removed from sampled gas; CO2 does not interfere with analysers
     VA,BTPS = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×(PB/(PB–47))×(310/(273+T))
     VA,STPD = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×(PB/760)×(273/(273+T))
    H2O and CO2 removed from sampled gas
     VA,BTPS = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr(1+FA,CO2)/FS,Tr)×(PB/(PB–47))×(310/(273+T))
     VA,STPD = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr(1+FA,CO2)/FS,Tr)×(PB/760)×(273/(273+T))
      If no measurement of FA,CO2 is available, then it may be assumed to be 0.05
    H2O in sampled gas equilibrated to room air; CO2 does not interfere with analysers. If FI,Tr is read by the analysers, the equations are the same as for when H2O is removed from sampled gas. If tank values (i.e. dry gas concentrations) are used for FI,Tr, then the following equations are used
     VA,BTPS = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×((PB–PH2O)/(PB–47))×(310/(273+T))
     VA,STPD = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×((PB–PH2O)/760)×(273/(273+T))
    Neither H2O nor CO2 removed from sampled gas, no interference with analysers, heated sample tubing to prevent condensation
     VA,BTPS = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×(310/(273+T))
     VA,STPD = (VI,ATPD–VD,INST–VD,ANAT)×(FI,Tr/FS,Tr)×((PB–47)/760)×(273/(273+T))
    • In these calculations, room temperature (T) is measured in Celsius and gas pressures are measured in mmHg. In all four cases, the inspired volume (VI) is the measured volume of inhaled dry gas and, thus, is considered under ambient temperature, ambient pressure, and dry (ATPD) conditions. The conversion to body temperature, ambient pressure, saturated with water vapour (BTPS) and standard temperature, pressure and dry (STPD) may require factors to compensate for the diluting or concentrating effects of adding or deleting H2O or CO2 at the gas sampling site. Therefore, standard gas condition conversion formulae must be adjusted as described previously. VA: alveolar volume; VD,INST: instrument dead space; VD,ANAT: anatomic dead space; FI,Tr: fraction of tracer (Tr) gas in the inspired test gas; FS,Tr: fraction of the Tr gas in the alveolar sample, which may differ from the fraction of alveolar Tr gas, depending on the effects of CO2 and H2O as noted; FA,CO2: fraction of CO2 in the alveolar sample.

  • Table. 6—

    Acceptable test criteria for diffusing capacity of the lung for carbon monoxide

    Use of proper quality-controlled equipment
    VI of >85% of largest VC in <4 s#
    A stable calculated breath hold for 10±2 s. There should be no evidence of leaks, or Valsalva or Mueller manoeuvres
    Expiration in <4 s (and sample collection time <3 s)#, with appropriate clearance of VD and proper sampling/analysis of alveolar gas
    • VI: inspired volume; VC: vital capacity; VD: dead space. #: tests outside these timing limits might still have clinical utility, but these deviations from standard acceptability criteria should be noted and possible impact/correction factors considered.

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Standardisation of the single-breath determination of carbon monoxide uptake in the lung
N. MacIntyre, R. O. Crapo, G. Viegi, D. C. Johnson, C. P. M. van der Grinten, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, P. Enright, P. Gustafsson, J. Hankinson, R. Jensen, R. McKay, M. R. Miller, D. Navajas, O. F. Pedersen, R. Pellegrino, J. Wanger
European Respiratory Journal Oct 2005, 26 (4) 720-735; DOI: 10.1183/09031936.05.00034905

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Standardisation of the single-breath determination of carbon monoxide uptake in the lung
N. MacIntyre, R. O. Crapo, G. Viegi, D. C. Johnson, C. P. M. van der Grinten, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, P. Enright, P. Gustafsson, J. Hankinson, R. Jensen, R. McKay, M. R. Miller, D. Navajas, O. F. Pedersen, R. Pellegrino, J. Wanger
European Respiratory Journal Oct 2005, 26 (4) 720-735; DOI: 10.1183/09031936.05.00034905
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  • Article
    • Abstract
    • BACKGROUND
    • GAS ANALYSERS AND GENERAL EQUIPMENT
    • SINGLE-BREATH TESTING TECHNIQUE STANDARDISATION ISSUES
    • CALCULATIONS
    • EVALUATING THE MEASUREMENT OF DL,CO
    • Reporting values
    • ABBREVIATIONS
    • Acknowledgments
    • Footnotes
    • References
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