Single-breath TLC measurements

I was reviewing the specifications of different pulmonary function test systems recently and saw that several manufacturers were advertising that some of their test systems are able to measure TLC, FRC and RV from a single-breath maneuver. This is true, but only to a very limited degree and I think it is reasonable to ask how accurate and clinically useful these measurements are and whether it is legitimate to bill for the test.

The measurement is made by having a patient exhale to RV and then inhale a gas mixture containing a tracer gas (an insoluble gas like helium or methane) to TLC. When the patient exhales, the degree by which the tracer has been diluted is then used to calculate the patient’s TLC. The math is quite simple and as is expressed as:

TLC = (inspired volume x (Fitrace/Fetrace)) – machine deadspace

This is done routinely as part of the DLCO test and there it is referred to as alveolar volume (VA) and it should be noted that all manufacturers are using the VA from the DLCO test as a substitute for TLC and are not performing single-breath TLC as a separate measurement.

The full panel of lung volumes is calculated from the overall breathing maneuver. When the patient exhales to RV, ERV is measured from end exhalation of the tidal breathing immediately beforehand. When the patient performs a inspired vital capacity, RV is calculated by subtracting the VC from the calculated TLC. FRC is then calculated by adding ERV to RV.

In patients with normal lungs the correlation between TLC measured by the single-breath method and by the helium dilution, nitrogen washout and plethysmographic methods is good. In patients with obstructive lung disease however, the correlation is poor and the TLC measured by the single-breath technique systematically underestimates the TLC obtained by other methods. This is attributed variously to maldistribution of inspired gas, gas trapping and poor gas mixing and has been common knowledge since at least the 1960’s.

More than one researcher has studied the relationship between the degree of airway obstruction as indicated by the FEV1/FVC ratio and single-breath TLC and then devised a correction factor. When applied to groups of patients these correction factors appear to work reasonably well but an inspection of the scatter of the results from these studies show that for an individual patient this is much less so. Part of this can be attributed to differences in a specific patient’s underlying lung disease, but there are also other confounding factors.

First, the FEV1/FVC ratio itself is dependent on patient effort and the FVC in particular is dependent on the length of time a patient is willing to exhale. In a patient with obstructive lung disease a given spirometry effort may be acceptable by ATS standards but can still underestimate FVC and therefore overestimate the FEV1/FVC ratio. So how accurate is the FEV1/FVC ratio when applied to correcting the single-breath TLC?

Second, none of the researchers studying single-breath TLC have shown any particular concern about inspired volume and its effect on the measurement of TLC. Their underlying assumption has been that all of their patients inhaled to TLC. They may have been correct, but in any given test how is this determined? The ATS/ERS standard for DLCO testing says that the inspired volume should be 85% of the patient’s largest known vital capacity. An acceptable DLCO effort can therefore have an end-inspiration that is 15% of the VC below TLC and when that happens the measured TLC will be likewise reduced.

Finally, the selection of washout volume and alveolar sample volume will affect the calculated single-breath TLC. In a patient with obstructive lung disease, likely because of maldistribution of the inspired gas mixture, the concentration of the tracer gas tends to decrease during exhalation. For this reason using a tracer gas concentration from the beginning of exhalation will lead to a calculated TLC that is lower than if taken from later in exhalation. TLC should be calculated by considering the average tracer gas concentration from the entire exhalation but the washout and sample volumes used to measure it are optimized for DLCO measurement, not TLC.

Single-breath TLC has not been studied in patients with restrictive lung diseases. Since these patient’s tend not be be obstructed it would be easy to assume that their single-breath TLC should be reasonably accurate. Maldistribution of ventilation however, does occur in these patients. I have personally seen a small number of patients with interstitial disease that have a pattern opposite to patients with obstruction where tracer gas concentrations are lowest at the beginning of exhalation and increase as exhalation continues. In these patients single-breath TLC may well be overestimated.

So, are single-breath TLC measurements accurate? Sorta. Sometimes. Maybe. They can be useful in quickly ruling out restrictive lung disease in some patients with a reduced FVC but the fact is that for any given patient there is going to be some uncertainty and that this level of uncertainty is going to be significantly greater for patients with obstructive lung disease. Correction factors are only guesses. Because the single-breath TLC cannot be counted on to produce reliable and accurate test results in my opinion it should neither be reported as part of a patient’s test results nor should it be billed. For the same reasons I also think it is misleading for equipment manufacturers to advertise this capability in any test system and that this practice should be ended.

References:

Burns, CB, Scheinhorn DJ. Evaluation of Single-breath Helium Dilution Total Lung Capacity is Obstructive Lung Disease. Amer Rev Resp Dis 1984; 130: 580-583.

Horstman MJM, Mertens FW, Schotborg D, Hoogsteden HC, Stam H. Comparison of Total-breath and Single-breath diffusing capacity in healty volunteers and COPD patients. Chest 2007; 131: 237-244.

Loiseau A, Loiseau P, Saumon G. A simple method for correcting single breath total lung capacity for underestimation. Thorax 1990; 45: 873-877.

MacIntyre N, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26: 720–735

Pesola GR,Magari RT, Dartey-Hayford S, Coelho-D’Costa V, Chinchilli VM. Total lung capacity: single breath methane dilution versus plethysmography in normals. Respirology. 2007; 12: 291-294.

Punjabi NM, Shade D, Wise RA. Correction of Single-breath Helium Lung Volumes in patients with Airflow Obstruction. Chest 1998; 114: 907-918.

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