Executive Summary: 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung

Methods

An application was submitted for a joint ERS/ATS task force to update the 2005 D_LCO standards [3] with a particular view to systems using RGAs. The task force co-chairs were approved by the ERS and the ATS while the task force members were scientists and physicians with experience in international guidelines, clinical experience of routine lung function testing and specialist knowledge of gas transfer (including research publications).

Potential conflicts of interest were disclosed and vetted. The task force consisted of five members of the task force for the 2005 D_LCO standards and four new members. A search using PubMed for literature published between 2000 and 2015 containing various terms related to diffusing capacity and transfer factor yielded 3637 citations. Task force members reviewed the abstracts and identified 113 as relevant to the project and a further 99 as potentially relevant. All manufacturers of pulmonary function equipment used to measure D_LCO were sent a survey requesting equipment specifications. Eight of the 13 manufacturers responded. A survey of D_LCO equipment specifications published on the manufacturers' websites was also conducted. Using the 2005 standards as a base document, revisions and additions were made on a consensus basis. The recommendations in this document represent a consensus of task force members in regard to the evidence available for various aspects of D_LCO measurement (as cited in the document) and reflect the expert opinion of the taskforce members for areas in which peer-reviewed evidence was either not available or incomplete. The task force also identified areas and directions for future research and development where evidence is lacking.

Equipment requirements

The equipment specifications and performance standards for D_LCO equipment are summarised in table 1.

Gas analysers

Rather than collecting a physical sample of exhaled gas, nondispersive infrared carbon monoxide RGAs are used to construct a virtual gas sample from flow and gas concentration data. However, in the signal from such analysers there is both a lag time (the time taken for sampled gas to travel through the sampling tube to the analyser chamber) and an analyser response time (the time taken to reach 90% of the actual measurement from the time the gas sample reaches the analyser) to be considered (figure 1). The gas concentration signal must be precisely shifted in time to align with the flow signal.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 1

Lag and response times for carbon monoxide: the response time of the analyser was estimated by rapidly switching the gas being sampled from zero to full-scale carbon monoxide. The change in the flow signal shows the time at which the switch was made from medical air to test gas. The lag time, the 0–90% response time and the optimal shift are calculated from the resulting response curve.

RGA response time

The response time of the RGA will determine how accurately it is able to track the true carbon monoxide and tracer gas concentrations. Even after the application of an appropriate time shift to correct for the lag and response times, there will be a residual error in D_LCO due to the finite response time. For every 100 ms increase in the 0–90% response time, the error in D_LCO increases by about 0.7% [6]. Based on the above considerations, the 0–90% response time for RGAs used in D_LCO systems must be ≤150 ms.

Linearity and accuracy

The linearity of the gas concentration signals is of primary importance for measuring D_LCO, since ratios of gas concentrations are considered in the classical calculations [7, 8]. The error in D_LCO measurement due to nonlinearity in the gas concentration signals depends on the size of the lungs and the rate of uptake of carbon monoxide. A nonlinearity of 0.5% of full scale can cause errors ranging from 0.5% in a subject with a D_LCO of 13.4 mmol·min⁻¹·kPa⁻¹ (40 mL·min⁻¹·mmHg⁻¹) to 1.7% in a subject with a D_LCO of 3.35 mmol·min⁻¹·kPa⁻¹ (10 mL·min⁻¹·mmHg⁻¹) [6]. The manufacturer specification for analyser linearity is that any nonlinearity must not exceed 0.5% of full scale once zero and full scale values have been set.

The accuracy of the gas analyser signal becomes important when measuring the residual alveolar carbon monoxide concentration and the washout of tracer gas from the previous D_LCO manoeuvre. The output of a gas analyser must be accurate to within ±1% of full scale.

Drift

The gas analyser should have only minimal drift in zero and gain, such that output is stable over the test interval. Gas analyser drift must be ≤10 ppm over 30 s for carbon monoxide and ≤0.5% of full scale over 30 s for tracer gas.

Digitisation

In order for the digitised signal to accurately track the gas concentration signal and to provide adequate opportunity for signal processing for data alignment, the minimum signal sampling rate must be ≥100 Hz per channel; however, a rate of 1000 Hz is recommended.

Other equipment considerations

Circuit resistance must be <1.5 cmH₂O·L⁻¹·s⁻¹ up to 6 L·s⁻¹ flow. If a demand-flow regulator is used on a compressed test gas cylinder, the maximal inspiratory pressure required for 6 L·s⁻¹ inspiratory flow through both circuit and valve must be <9 cmH₂O.

The equipment dead-space volume (V_Dequip) for both the inspired test gas and the alveolar sample must be known and their role in all data-computation algorithms should be identified and documented. For adults, the V_Dequip must be <200 mL including the breathing circuit proximal to the gas analyser sampling point, filter and mouthpiece. Smaller dead-space volumes are recommended for paediatric applications and people with a vital capacity (VC) of less than 2 L.

Equipment calibration and quality control

The considerations for equipment calibration are illustrated in table 2 and are summarised as follows:

1) Flow and gas analysers must be zeroed prior to each manoeuvre. After each manoeuvre, a new zeroing procedure must be carried out to account for analyser drift during the previous test.

2) Each day, prior to testing, there must be a volume calibration check with a 3-L syringe [9]. The syringe should be discharged at least three times to give a range of flows varying between 0.5 and 12 L·s⁻¹ (with 3-L injection times of ∼6 s and ∼0.5 s, respectively). The volume at each flow must meet an accuracy requirement of ≤2.5% error. For devices using disposable flow sensors, a new sensor from the supply used for patient tests must be tested each day. The calibration check may need to be repeated during the day if ambient conditions change. Newer systems monitor ambient conditions and make adjustments as necessary or produce a calibration alert when needed. Older systems may require a calibration check if room temperature changes by more than 3 °C or relative humidity changes by more than 15% (absolute). Operators should also perform a calibration check whenever they notice significant discrepancies between inspired volume (V_I) and VC, or between alveolar volume (V_A) and total lung capacity (TLC), which might suggest volume calibration problems.

3) Each week, or whenever problems are suspected, the following procedures must be followed. First, for those D_LCO systems using a volume-type spirometer, a spirometer leak test should be performed according to the manufacturer's specifications. Secondly, a D_LCO test should be performed with a calibrated 3-L syringe by attaching the syringe to the instrument in the normal patient test mode. The syringe is then emptied, filled with 3 L of test gas and then emptied into the mouthpiece after the 10 s breath-hold. The calculation of V_A must be within 300 mL of 3 L times the ATPD to BTPS (body temperature, ambient pressure, saturated with water vapour conditions) correction factor, which is 310/T_A·P_B/(P_B−47), where T_A is the ambient temperature in degrees kelvin and P_B is the barometric pressure in mmHg. It should be noted that a 3 L calibration syringe will have an additional dead-space which, depending on the connection to the mouthpiece, is typically ∼50 mL and must be considered in the V_A calculation. The absolute value of the calculated D_LCO must be <0.166 mmol·min⁻¹·kPa⁻¹ or <0.5 mL·min⁻¹·mmHg⁻¹. Thirdly, a test should be performed on a “standard subject” (biological control) or simulator [10]. Standard subjects are nonsmokers who have been found to have a consistently repeatable D_LCO (e.g. healthy laboratory personnel). If the D_LCO in a standard subject varies either by >12% or by >1 mmol·min⁻¹·kPa⁻¹ (>3 mL·min⁻¹·mmHg⁻¹) from the mean of previous values, the test must be repeated. A study of the long-term intersession variability of D_LCO has found that biological control deviations of >12% or >3 mL·min⁻¹·mmHg⁻¹ from the average of the first six tests indicate that the instrument is not within quality control limits and must be carefully evaluated before further patient testing [11].

4) Each month a leak test of the 3-L calibration syringe should be performed. If the calibration syringe does not have a volume scale on the shaft, mark 50 mL below full by measuring the excursion of the shaft from 0 to 3 L and marking it at a distance that is 0.017 of the full excursion. Fill the syringe and place a stopper at the syringe input. Push the syringe in to the 50 mL mark (which generates a pressure of about 17 cmH₂O), hold for 10 s and release. If the syringe does not return to within 10 mL of the full position, it should be sent for repair. The procedure is then repeated starting with the syringe at 50 mL below full, applying the stopper and pulling the syringe to the full position.

5) Each month, gas-analyser linearity should be assessed. A straightforward approach is to measure known serial dilutions of the test gas [12], or to measure the concentration of a separate high-precision test gas having a certificate of analysis. For systems with independent measurements of carbon monoxide and tracer gas, the analyser linearity may also be assessed by comparing the ratio of carbon monoxide and tracer gas concentration to arbitrary dilutions of test gas with room air. A third type of calibration syringe test, which differs from the volume and D_LCO checks above by using the 3-L syringe in ambient temperature, pressure and humidity (ATP) mode, may also reveal problems with analyser linearity. With approximately 1 L of air in the syringe, the test begins by filling the remaining volume with test gas. Following a 10 s “breath-hold”, the syringe is then emptied. The calculation of V_A must be within 300 mL of 3 L with the syringe dead-space being used for the anatomic dead-space in the V_A calculation. The absolute value of D_LCO must be <0.166 mmol·min⁻¹·kPa⁻¹ or <0.5 mL·min⁻¹·mmHg⁻¹. A review of quality control data for four different D_LCO systems between 2006 and 2015 using this procedure found only four outlier points where |D_LCO| was >0.13 mmol·min⁻¹·kPa⁻¹ (0.4 mL·min⁻¹·mmHg⁻¹). The same data showed that V_A was consistently within 3±0.3 L for four systems (unpublished data from B.R. Thompson). Gas mixing in the syringe can be improved by using low flow rates and extending the breath-hold time. The effects of incomplete mixing in the syringe can be minimised by using a larger sample volume. In the absence of a D_LCO simulator and high-precision test gases, system checks must be performed using a 3-L calibrating syringe in ATP mode. Manufacturers must provide this test option, which will be the same as the usual testing procedure for a patient, with the exception that V_A will be reported under ATP rather than BTPS.

6) A record of equipment checks and standard subject tests should be dated and kept in a laboratory log book or digital file folder. Manufacturers are encouraged to provide software and test equipment options for quality control measurements and quality control data management. In addition, manufacturers may provide equipment-specific, quality-control measures in addition to the foregoing points. If water vapour permeable tubing is used to either remove water vapour or equilibrate water vapour with room air, such tubing must be replaced according to manufacturer recommendations to ensure that it is functioning properly. Chemical gas analyser cells will have a replacement schedule. Manufacturers may also have preventative maintenance schedules for various other system components (e.g. balloon valves) which will require testing and replacement as necessary.

Patient condition

Before beginning the test, the manoeuvres must be demonstrated and the subject carefully instructed. The subject must be seated comfortably throughout the test procedure. The test must be performed at a stable, comfortable temperature within manufacturer's equipment specifications.

Inspiratory manoeuvres

Once the mouthpiece and nose clip are in place, tidal breathing must be carried out for sufficient time to ensure that the subject is comfortable with the mouthpiece and that the nose clips and mouthpiece are used appropriately with no leaks. The D_LCO manoeuvre begins with unforced exhalation to residual volume (RV). In obstructive lung disease, where exhalation to RV may require a prolonged period, a reasonable recommendation is that this portion of the manoeuvre must be limited to <12 s. Exhalation times of up to 12 s will allow most patients with airflow obstruction to exhale sufficiently so that they can achieve a maximal VC during the subsequent inhalation of test gas. Submaximal inhalation occurs most frequently in patients with airflow obstruction who are not given adequate time to exhale prior to the inhalation of test gas. At RV, the subject's mouthpiece is connected to a source of test gas, and the subject inhales rapidly to TLC. It is important that the inspired volume of test gas, V_I, be as close to the known VC as possible and V_I must be at least 90% of the largest VC in the same pulmonary function testing session. However, a manoeuvre may be deemed to be acceptable if V_I is within 85% of the largest VC and V_A is within 200 mL or 5% (whichever is greater) of the highest V_A among acceptable D_LCO manoeuvres.

Washout and sample collection

For RGA systems, the point of dead-space washout can be determined from the expired tracer gas concentration data using an objective algorithm. The beginning of the alveolar plateau can be located by determining the breakpoint of each phase of the washout (a plot of concentration versus volume) and adding a proportion of the dead-space volume measured by the Fowler technique [13] to the phase II to III breakpoint [14]. Such an approach can be automated. For visual verification of the point of dead-space washout, the tracer gas concentration must be displayed as a function of volume, since using the concentration–time curve can be deceptive because of the higher relative flow at the beginning of exhalation (figure 2). If the sample collection point is changed by the operator, it must be recorded in the database and on the report.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 2

Comparison of gas concentration plotted as a function of time (a and b) or volume (c and d) for carbon monoxide and tracer gas. The shaded bar shows the collection of a 500-mL sample of exhaled gas. The upper panels (a and c) show sample collection as selected by computer algorithm (based on gas concentration and lung volume). The lower panels (b and d) show sample collection after manual adjustment by an operator using the concentration versus time plot. Operators tend to be more conservative and may over-shift the sample. When gas concentration is plotted against time, the shift does not appear to be significant; however, when gas concentration is plotted against volume, the degree of shift becomes more apparent.

With RGA systems, the concentrations of carbon monoxide and tracer gas in a virtual alveolar gas sample can be calculated for use in measuring D_LCO; however, RGA systems are capable of simulating much smaller gas samples although it should be noted that such smaller virtual samples will be more subject to noise in the expired carbon monoxide concentration signal. Indeed, Jones and Meade [15] used gas samples of 85 mL in the development of their method and virtual alveolar gas sample volumes of 85–500 mL may be used.

Inspired gas composition

The test gas used to calculate D_LCO should contain very close to 0.3% carbon monoxide, 21% oxygen, a tracer gas and a balance of nitrogen. The tracer gas must be relatively insoluble and relatively chemically and biologically inert. The inspired carbon monoxide concentration should thus be close to 0.3%. There are two factors determining the rationale for the recommendation of an inspiratory oxygen fraction (F_IO2) of 21% in the test gas for routine D_LCO determination. First, the majority of studies developing reference values for D_LCO, which are based on the 2005 standards [4], use an F_IO2 of 21% (see the section on reference values below). Secondly, the P_AO2 (alveolar oxygen tension) following a maximal inhalation will depend on the dead-space volume and the ratio of V_I to V_A for any given F_IO2 in the test gas. Hence if reducing F_IO2 in the test gas is intended to simulate tidal breathing conditions (i.e. P_AO2 of 100 mmHg or 13 kPa), it may not do so in all subjects.

Manoeuvre intervals

Using an RGA system, exhaled gas can be monitored as soon as the subject begins breathing through the mouthpiece prior to the inhalation of test gas. This “end-expiratory” tracer gas information will indicate whether or not the washout from a previous manoeuvre is complete, which may occur in less than 4 min in some subjects. The tracer gas concentration at end-exhalation must be ≤2% of the tracer gas concentration in the test gas. Occasionally, if a subject has not reached this level of washout after 5 min, the operator may have the option of continuing with the next manoeuvre. However, in either event, the end-expiratory tracer gas concentration must be reported and used to compensate the tracer gas concentration data used in the determination of V_A at the beginning of breath-holding.

Calculating the alveolar volume

Using RGA systems, the dead-space volume is measured rather than estimated. The total dead-space, V_D, can be obtained from the tracer gas washout curve using the Fowler method (figure 3) [13]. The development of RGA systems allows for the analysis of all of the exhaled gas and, since the tracer gas is being monitored throughout exhalation, there is no need to constrain the measurement of V_A to the discrete sample computationally constructed for determining carbon monoxide uptake. This provides the opportunity to enhance the accuracy of V_A determination and, indeed, using all of the available gas concentration data has been shown to provide a better estimate of V_A [16, 17] than constraining measurement to smaller samples of exhaled gas, as required by the equipment available in 1957 when the clinical single-breath method was developed [1].

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 3

Graphical representation of the calculation of the Fowler dead-space volume in a normal, healthy subject (a) and a subject with chronic obstructive pulmonary disease (COPD) (b). The single-breath tracer gas washout is plotted against exhaled lung volume from total lung capacity. The volume at which the shaded area above the tracer gas washout curve equals the shaded area below the curve is the Fowler dead-space [13] which is reported under body temperature, ambient pressure, saturated with water vapour (BTPS) conditions.

This approach uses a mass balance technique in which the volume of tracer gas inhaled and subsequently exhaled are measured, such that the volume of tracer gas remaining in the lung at end-exhalation is known [16, 17]. The volume of tracer gas left in the lung is divided by the end-expiratory tracer gas concentration to measure the absolute end-expiratory lung volume. Total lung capacity is then calculated by adding the expired volume to the end-expiratory volume and subtracting equipment dead-space. The residual tracer gas in the lung from a previous manoeuvre, if any, can be measured prior to the start of the manoeuvre and included in the mass balance equation.

RGA signal alignment

To properly analyse continuous gas samples, the gas concentration signal from the analyser must be properly aligned with the flow signal from the pneumotachometer. The first step is to shift the concentration signal ahead in time to compensate for the lag time (figure 1). The lag time refers to the time required for the gas to travel from the aspiration port to the analyser chamber and is a function of the length and diameter of the tubing and the analyser aspiration rate. The length of the tubing should be minimised to prevent mixing of the aspirated sample within the sampling tube, which can blunt the response time through a process of Taylor dispersion. The amount of mixing will also depend on the configuration of the sampling circuit, including any valves or junctions that create turbulence. Lag time can also vary with the viscosity of the gas and as such, when helium is used as the tracer, dynamic compensation of the lag time may be required during exhalation. An additional shift of each gas concentration signal relative to the flow signal must also be performed to compensate for the response time of the analyser. This adjustment can be performed using an optimal shift equal to the natural logarithm of twice the time constant of the analyser response [18]. Alternatively, alignment may be achieved by other signal processing techniques, such as cross-correlation (convolution of signals).

Acceptability, repeatability and quality control

The volume–time graph for a manoeuvre should show a smooth, sharp rise in volume, followed by a stable breath-hold and a smooth, sharp exhalation. The gas concentration graph should show a very sharp rise when test gas is introduced and remain stable until exhalation followed by an initial rapid decline with a smooth transition to phase III. Variations from this pattern will indicate leaks. Acceptable manoeuvres are defined in table 3. The V_I of test gas must be at least 90% of the highest VC measured in the same pulmonary function testing session. At least 85% of test gas V_I must be inhaled 4 s and there must be no evidence of a Müller or Valsalva manoeuvre during the breath-hold period. The calculated breath-hold time must be 10±2 s and the alveolar sample collection must be completed within 4 s. For RGA systems, the virtual sample collection must be initiated after the completion of dead-space washout. A manoeuvre with a V_I/VC <90% but ≥85% may be deemed acceptable if the V_A is within 200 mL or 5%, whichever is greater, of another acceptable manoeuvre.

Repeatability describes the intra-session variability on repeat testing when there is no change in test conditions [19, 20]. In a large university-based laboratory study, the coefficient of variation for repeat measurement in normal subjects was reported as 3.1% and this increased only slightly (from 4.0–4.4%) in patients with abnormal spirometry patterns [21]. Studies conducted prior to the publication of the 2005 standards found D_LCO variability of up to 9% (reproducibility) in normal individuals in repeat measurement over a period of 1 year [22] and coefficients of variation ranged from 6.2–12% for selected UK regions [23].

Repeatability requirement: there must be at least two acceptable manoeuvres that are within 2 mL·min⁻¹·mmHg⁻¹ (0.67 mmol·min⁻¹·kPa⁻¹) of each other. A study of 4797 test sessions found that 95.5% of cases met this criterion [24]. Since most intra-session variability is technical rather than physiological, the mean of acceptable manoeuvres is reported. The average of at least two acceptable manoeuvres that meet the repeatability requirement must be reported (i.e. outliers excluded). While it is recommended that at least two acceptable D_LCO manoeuvres must be performed, research is needed to determine the actual number of manoeuvres required to provide a reasonable estimate of average D_LCO for a given person. As noted elsewhere, five manoeuvres will result in an increase of ∼3.5% carboxyhaemoglobin (COHb) from baseline [25, 26], which will decrease the measured D_LCO by ∼3–3.5%. Thus, conducting more than five manoeuvres is not a recommended strategy.

There are no quality control grading systems that have been validated using the new standards contained in this document. Until such validation is published, an interim grading system is provided in table 3 and further research is recommended to develop and validate a D_LCO grading system.

A grade A manoeuvre meets all acceptability criteria. The average D_LCO from two or more grade A manoeuvres that are repeatable (i.e. are within 2 mL·min⁻¹·mmHg⁻¹ or 0.67 mmol·min⁻¹·kPa⁻¹ of each other) should be reported. If, after repeat testing, the operator is unable to obtain two repeatable grade A manoeuvres, then the following values are reported with a caution to the interpreter that the testing session was suboptimal: 1) If two or more grade A manoeuvres that are not repeatable are obtained, then the average D_LCO value from the acceptable manoeuvres is reported. 2) If only one grade A manoeuvre is obtained, then the D_LCO value from that manoeuvre is reported. 3) If no acceptable manoeuvres are obtained, then the average D_LCO value of the manoeuvres with grades B, C or D is reported. 4) If only grade F manoeuvres are obtained then no D_LCO value is reported.

Adjustments to the predicted value of D_LCO prior to interpretation

The value of D_LCO depends upon a number of physiological factors. Besides varying with age, sex, height and possibly ethnicity, D_LCO also changes with lung volume, Hb (haemoglobin) and COHb level, P_IO2 (inspired oxygen tension, e.g. altitude), exercise and body position.

Adjustment for haemoglobin

Using the Cotes equations [27] and assuming the “standard” Hb value to be 14.6 g·dL⁻¹ in adult and adolescent males and 13.4 g·dL⁻¹ in adult females and children <15 years of age, the adjustment to the predicted D_LCO value of the former is described by equation 3 while the adjustment to the latter is described by equation 4.

3 4

Measurement of Hb in the American population [28] indicated difference from these “standard” values, especial in males, children and seniors; differences were also reported between Caucasian and African-Americans. Furthermore, the survey found that Hb levels in the general population were changing over time. If a more appropriate reference Hb level (Hb_ref) is available, then the predicted D_LCO value is adjusted as in equation 5.

5

Adjustment for carboxyhaemoglobin concentration and carbon monoxide back-pressure

The level of COHb can affect the measured uptake of carbon monoxide in two ways [29–31]. First, by occupying Hb binding sites, carbon monoxide produces an “anaemia effect”. Secondly, carbon monoxide partial pressure in the blood will reduce the driving pressure for carbon monoxide transport from alveolar gas to capillary blood.

For RGA systems, carbon monoxide back-pressure can be measured in expired gas prior to the inspiration of test gas in the D_LCO manoeuvre [32] and analytically compensated for by subtracting the estimated carbon monoxide back-pressure from both the initial and final alveolar carbon monoxide partial pressures. However, this method will not adjust D_LCO for the “anaemia effect” effect of COHb.

A recent study using an RGA system to measure alveolar carbon monoxide concentration combined with venous measurements of COHb found that the effect of carbon monoxide back-pressure and the “anaemia effect” are almost equal and the combined effect is a 2% decrease in D_LCO for each 1% increase in COHb [32]. These findings were verified in a discrete-sample system [26]. In these studies, where the carbon monoxide back-pressure was measured and used in the calculation of D_LCO, equation 6 was used to further correct for the anaemia effect, where F_ACOb is the alveolar carbon monoxide fraction in ppm measured at the end of exhalation to residual gas volume, just prior to the inhalation of test gas.

6

Adjustment of D_LCO for barometric pressure

While the preceding adjustments are made to the predicted value of D_LCO, it is recommended that the measured value of D_LCO be adjusted for barometric pressure. As P_B decreases, P_IO2 decreases and D_LCO increases. For factors such as Hb that are related to the individual subject, the recommended adjustment is made to the predicted D_LCO value. However, P_B is an environmental factor that is independent of the individual and therefore the measurement of D_LCO should be adjusted to simulate standard pressure conditions. The variation in D_LCO due to the typical range of high and low pressure cells at a given altitude is approximately ±1.5%. As mentioned above, as P_B decreases with altitude, D_LCO increases. The rate of change is about 0.53% for each 100 m of increase in altitude. Moreover, the applicability of using a reference value data set from a different location is improved if both the measured D_LCO and the predicted value of D_LCO are adjusted to a standard pressure (101.3 kPa or 760 mmHg). The adjustment for P_B [3, 33] assumes a P_IO2 of 20 kPa (150 mmHg) at standard pressure and the adjusted value of D_LCO is thus described by equation 7 (P_B in mmHg) or equation 8 (P_B in kPa).

7

8

Reporting values

This document is intended to establish technical standards which, in terms of reporting, will require D_LCO systems to be able to report the variables shown in table 4. It is not intended to specify which variables end users should include in the report forms used in their laboratories, nor is it intended to address the interpretation of D_LCO. Although work is ongoing towards establishing a standardised pulmonary function laboratory report form, there is no current standard. A D_LCO system must be able to report the unadjusted measured D_LCO, the D_LCO adjusted for P_B, the lower limit of normal and z-score, predicted, and percentage of predicted D_LCO values. They must also be able to report the carbon monoxide transfer coefficient, K_CO, which is the logarithmic decay of carbon monoxide concentration over t_BH per unit of pressure, as well as the lower limit of normal and z-score, predicted, and percentage of predicted K_CO values. Any adjustments (e.g. for Hb, COHb, P_IO2, or lung volume) must also be reported along with the data used to make the adjustment. The average V_A must be reported along with the predicted V_A (the predicted TLC minus the predicted V_D) and percentage of predicted V_A. If available, a separately measured TLC and V_A/TLC ratio may optionally be reported. The average V_I must also be noted. If a separately measured VC is available, it can be reported to serve as a reference for the adequacy of the V_I value. In addition, comments relevant to the quality of the measurements must be included. A complete list of specifications for which variables and measurements D_LCO systems should be able to report is given in table 4. While the use of z-scores is favoured in the interpretation of pulmonary function results, given the continuing use of percentage of predicted values in many laboratories, the ability to report both z-scores and percentage of predicted values is recommended.

The Global Lung Health Initiative (GLI) is currently working on the development of global reference values for D_LCO which will very likely be of a similar structure to the GLI spirometry reference values [34]. Implementation of these reference values requires more complexity than simply inserting coefficients for polynomials and a D_LCO system must be able to implement this method of calculating reference values.