Calculating VA the mass balance way

One of the more significant changes that appeared in the 2017 ERS/ATS DLCO standards was the requirement that rapid-response gas analyzer (RGA) systems calculate VA using a mass balance approach. This is actually more straightforward than it sounds but it does raise several issues that weren’t fully addressed in the 2017 standards.

Up until this time VA has been calculated from the inspired volume and by the amount of dilution of the tracer gas in the exhaled alveolar sample. Specifically:

 

Which is described by:

Where:

VI = inspired volume

Vd = Anatomical and Machine deadspace

Fitrace = Inspired tracer gas concentration

FAtrace = Exhaled tracer gas concentration

The basic concept behind the mass balance approach to measuring VA is relatively simple and is described in the 2017 standard as:

…the tracer gas left in the lung at end exhalation is equal to all of the tracer gas inhaled minus the tracer gas exhaled.”

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ERS/ATS 2017 DLCO standards

The new ERS/ATS standards for DLCO testing were published in the January issue of the European Respiratory Journal. The article was published as open access and can be downloaded from the ERJ website.

The biggest difference between the new standards and those from 2005 is that they are now primarily oriented towards Rapid-response Gas Analyzers (RGA). The authors explicitly state that the new standards do not make older systems that use discrete alveolar sampling and slower gas analyzers obsolete, but many of the new suggestions and requirements for labs and manufacturers require systems with a RGA.

The differences between the 2017 and 2005 standards that I’ve been able to find include:

♦ Flow accuracy was not specified in the 2005 standard but is now required to be ± 2% over a range of ± 10 L/sec.

♦ Volume accuracy is now required to be ± 2.5% (± 75 ml) instead of ± 3.5%. Notably the 2005 standard included a ± 0.5% error in the calibrating syringe. The accuracy of the 3-liter syringe is now stated separately. In the 2005 standard volume accuracy was over an 8-liter range. No volume range is specified in the 2017 standard.

♦ RGA response time (analyzer rise time) had not previously been specified but is now required to be ≤150 milliseconds. Sample transit time was discussed but no specific recommendations were made. Sample transport issues such as Taylor dispersion, gas viscosity and turbulence at gas fittings was also discussed and although it was suggested that manufacturers attempt to minimize these effects no specific recommendations were made.

♦ Analyzer linearity for both RGA and discrete sample systems has been relaxed to ± 1.0% in the 2017 standards from ± 0.5% in the 2005 standards.

♦ CO analyzer accuracy for both RGA and discrete sample systems is now specified as ≤10 ppm (which is ±0.3% of 0.3% CO). It was previously specified as ± 0.0015% (which is ± 0.5% of 0.3% CO).

♦ Interference from CO2 and water vapor for both RGA and discrete sample systems is now specified as ≤10 ppm error in CO (when CO2 and water vapor are ≤5%). Interference was recognized as a problem in the 2005 standard but error limits were not specified.

♦ Digital sampling rate was not discussed or specified in the 2005 standards. It is now specified as a minimum of ≥100 hz with a resolution of 14 bits. A 1000 hz sampling rate is recommended.
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New Year’s Resolutions for a better PFT lab

It’s a tradition to come up with New Year’s resolution in order to improve ourselves. How about some resolutions to improve our labs?

1. Review and update the procedure manual

When was the last time you reviewed your procedure manual? Procedure manuals should be reviewed by the lab manager and medical director annually. It’s time to re-read the ATS/ERS guidelines and then review and update your procedure manual. Both your old staff and your new staff need to know what to do and how to do it. Your procedure manual is also going to be the first thing that anybody looks at if your lab is ever inspected.

2. Biological QC

Daily calibrations (and you’re doing daily calibrations and keeping a log of them, aren’t you?) are not enough to make sure our test systems are operating correctly. Regular (weekly, bi-weekly or monthly) biological quality control on ourselves with a Levey-Jennings chart is still the best way to do this. Don’t put it off. Biological QC is not an option; it’s a minimum requirement for any medical lab.
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Is there airway obstruction when the FEV1 is normal?

I’ve been reviewing the literature on PFT interpretation lately and in doing so I ran across one of the issues that’s bothered me for a while. Specifically, my lab has been tasked with following the 2005 ATS/ERS guidelines for interpretation and using this algorithm these results:

Observed: %Predicted: LLN: Predicted:
FVC: 2.83 120% 1.76 2.36
FEV1: 1.77 100% 1.26 1.76
FEV1/FVC: 63 84% 65 75

would be read as mild airway obstruction.

Although it’s seems odd to have to call a normal FEV1 as obstruction I’ve been mostly okay with this since my lab has a number of patients with asthma whose best FVC and FEV1 obtained at some point in the past were 120% of predicted or greater but whose FEV1 frequently declines to 90% or 100% of predicted. In these cases since prior studies showed a normal FEV1/FVC ratio then an interpretation of a mild OVD is probably correct even though the FEV1 itself is well above the LLN, and this is actually the situation for this example.
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Fick Cardiac Output

We’ve all run across the Fick equation for cardiac output at one time or another. There are very limited circumstances when we’d ever get to use it but at the same time it’s one of those simple but incredibly profound equations that’s also a foundation of pulmonary physiology.

The Fick equation is:

where:

VO2 = oxygen uptake

CvO2 = mixed venous oxygen content

CaO2 = arterial oxygen content

And what it describes is:

It’s a mass-balance equation that basically says that what goes in must come out, but how do you get from oxygen uptake to cardiac output?
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N2 washout troubleshooting

I was recently contacted by the manager of a lab that was having problems with their N2 washout lung volumes. Specifically, their N2 washout lung volumes (FRC in particular) were coming out low and everyone being tested on the system looked like they had restriction. The system has been checked by the manufacturer’s service techs several times and they’d replaced the tubing, the O2 tank and a number of parts. Service first asked them to wait between tests and then not to bother. Most lately they’ve been asked to calibrate the system before each test. Despite all this, their system continues to under-estimate lung volumes.

We’ve all had seemingly intractable problems with our test systems at one time or another. Sometimes they’re problems that can only be fixed by replacing major components, such as a gas analyzer or a motherboard. Sometimes they turn out to be something simple that nobody noticed despite looking straight at it numerous times. Experience and good technical support helps, but for every test system there has to be at least a couple of problems that are either uncommon, difficult to diagnose or are happening for the first time. When this happens it’s best to go back to basics and try to see what it is that’s most likely to explain the symptoms.

N2 washout lung volume measurements measure the amount of nitrogen residing in the lung and use this to estimate the volume of the entire lung. Closed circuit lung volume measurements using nitrogen were first attempted in 1932 by Christie. Christie’s approach used a known volume of oxygen to dilute the nitrogen in the lung but accuracy was limited at least in part because the amount of oxygen in the closed circuit was constantly changing due to the subject’s oxygen uptake. In 1940 Darling et al demonstrated an open circuit technique that is the basis for current N2 washout tests. In this approach the nitrogen in a subject’s lung was washed out with 100% O2 and their exhaled air was collected in a Tissot spirometer. After a certain amount of time (nominally 7 minutes) the exhaled volume and the N2 concentration in the Tissot spirometer was measured. The amount of nitrogen that had been exhaled is then calculated using simple math and the subject’s FRC is estimated from that.

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Estimated Lung Age (ELA)

Cigarette smoking raises the probability that an individual will get lung cancer, chronic bronchitis and/or emphysema (among many other things). Nicotine is addictive and smokers often need significant motivation in order to quit. Lung age is a tool that was designed to give smokers an additional incentive to do this. The concept is fairly simple and that is by reformulating an FEV1 reference equation it is possible to take an individual’s actual FEV1 and estimate the age of their lungs (ELA). Because cigarette smoking can cause airway obstruction it tends to mimic premature lung aging which means that when a smoker’s FEV1 is used to calculate an ELA it can be significantly greater than their real or chronological lung age (CLA).

This idea was first proposed by Morris and Temple in 1985. Using Morris et al’s 1971 spirometry reference equations they studied the effect of calculating an estimated lung age (ELA) using observed FVC, FEV1 and FEF25-75 values both singly and in combinations and found that the FEV1 had the lowest standard error. The ELA calculation based on Morris et al’s FEV1 reference equations has achieved a degree of popularity and is available on at least one personal spirometer (Pulmolife, sold by Carefusion, MDSpiro and Vitalograph) and as an on-line calculator from a couple different websites (Chestx-ray.com and Lung Foundation of Australia).

Interestingly, the effectiveness of ELA towards quitting smoking has been studied only a handful of times. One often-quoted study of smoking cessation (Parkes et al) saw double the quit rate (13.6% vs 6.4%) when ELA was used as an intervention but the study’s methodology has since been criticized and it’s results have not been duplicated.

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Flow-volume loops are timeless

Recently I’ve been trying to help somebody whose spirometry results changed drastically depending on where their tests were performed. When their spirometry was performed on an office spirometer their FVC was less than 60% of predicted and when they were performed in a PFT lab on a multi-purpose test system their FVC was closer to 90% of predicted. Part of the reason for this was that different predicted equations are being used in each location but even so there was about a 1.5 liter difference in FVC.

One important clue is that the reports from the office spirometer showed an expiratory time of around 2 to 2-1/2 seconds while the reports from the PFT lab showed expiratory times from 9 to 12 seconds. The reports from both locations however, only had flow-volume loops and reported expiratory time numerically. There were no volume-time curves so it isn’t possible to verify that the spirometry being performed at either location was measuring time correctly or to say much about test quality.

The shape of a flow-volume loop is often quite diagnostic and many lung disorders are associated with very distinct and specific contours. Volume-time curves, on the other hand, are very old-school and are the original way that spirometry was recorded. The contours of volume-time curves are not terribly diagnostic or distinctive and I suspect they are often included as a report option more because of tradition than any thing else. But volume-time curves are actually a critically important tool for assessing the quality of spirometry and one of the most important reasons for this is because there is no time in a flow-volume loop.

With this in mind, the following flow-volume loop came across my desk yesterday. The FVC, FEV1 and FEV1/FVC ratio were all normal and it was the best of the patient’s efforts.

fvl_timeless

The contour of this flow-volume loop is actually reasonably normal, except possibly for the little blip at the end.
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IC, ERV and the FVC

While reviewing reports today I ran across a couple of lung volume tests from different patients where the SVC was over a liter less than the FVC. Suboptimal SVC measurement can affect both the TLC and the RV and in one case the TLC was slightly below normal (78% of predicted) and in the other the TLC was within normal limits but the RV was over 150% of predicted. Both patients had had lung volume measurements previously and the current TLC was significantly different than it had been before.

I seem to run across this problem at least once a week so I am reasonably used to making manual corrections. I’ve discussed this previously but basically I use the position of the tidal loop within the maximal flow-volume loop obtained during spirometry to determine IC and ERV and then re-calculate TLC and RV accordingly.

fvl_tvl_4

Anyway, for this reason I had tidal loops, and IC and ERV on my mind while I was reviewing other reports. Shortly after this I came across a report that had “fair FVC test quality and reproducibility” in the tech notes so I pulled up the raw spirometry test data and took a closer look.

What I found was that the patient had performed five spirometry efforts and that the FVC and FEV1 was different on each test. All five spirometry efforts met the ATS/ERS criteria for back-extrapolation, expiratory time and end-of-test flow rates. I clicked back and forth between the different spirometry efforts to make sure the right FVC and FEV1 had been selected and when I did I noticed that the position of the tidal loop was shifting left and right and that the closer it was to TLC, the lower the FVC and FEV1 were and vice versa.

fvl_tvl_1

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The dual tracer gas single-breath washout (DTG-SBW) and ventilation inhomogeneity

I’ve been interested in ventilation inhomogeneity for a while and as ways to measure it I have looked at VA/TLC ratios, the Lung Clearance Index (LCI) and the phase III slope of the single-breath N2 washout (SIIIN2). All of these tests are able to provide some information about ventilation inhomogeneity but each has their own limitations and just as importantly although their results have a relatively clear relationship with ventilation inhomogeneity it’s not quite as clear what exactly it is they are measuring. A friend recently pointed me to an on-line article in Chest that discusses the dual-tracer single-breath washout test in patients with COPD. The apparent advantage of this test is that it is able to provide information about the site of the ventilation inhomogeneity. Although dual tracer gases have been used to study airway function for over 50 years the limitation of this technique has been the need to use a mass spectrometer. Some recent advances in technology have made it possible for this type of testing to be performed with a significantly less expensive gas analyzer and this has revived an interest in the dual-tracer gas single-breath washout (DTG-SBW).

The two tracer gases in question are Helium and Sulfur Hexaflouride (SF6). Helium has a density of 4 gm/mol and the density of SF6 is 146 gm/mol, and it is the difference in densities between these two inert and insoluble gases that make this test useful. In order to understand why we need to revisit to the anatomy of the terminal airways.

From Osborne S. Airway resistance and airflow through the tracheobronchial tree. www.SallyOsborne.com.

From Osborne S. Airway resistance and airflow through the tracheobronchial tree. www.SallyOsborne.com.

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