One of the hallmarks of chronic asthma is airway inflammation. This frequently causes an increase in the perfusion of the airways which in turn can appear as an increased DLCO in routine PFTs. A number of investigators have noted that this inflammation can also cause an increase in exhaled air temperature. This increase in exhaled air temperature is not due to an increase in body temperature but to increase in the rate of heat exchange between the airways and respired air due to the increased airway perfusion.
Because the increase in exhaled air temperature also correlates reasonably well with exhaled Nitric Oxide (NO) levels it would seem that measuring exhaled air temperature as part of spirometry or other pulmonary function testing could either act as a substitute for exhaled NO measurements or at least indicate which patients would benefit the most from exhaled NO measurements. It turns out however, that making these measurements is a lot more complicated than it would appear at first glance.
The most important factor that makes exhaled temperature difficult to measure is that it varies throughout exhalation. This has lead to two different approaches to measuring exhaled air temperature. First by measuring the rate at which exhaled air temperature changes during a slow exhalation. Second, by measuring the plateau temperature (PLET) which usually occurs near the end of exhalation and also usually from a slow, controlled exhalation.
The manager of a nearby PFT Lab made an interesting statement recently, and that was that DLCO measurements made with a sample balloon were superior to those made with a real-time gas analyzer. I think that he is biased to some extent by the fact that the manufacturer of his lab’s testing systems only supports the sample balloon approach to DLCO testing and so that is what he is used to. The same can be said of me however, because all of my lab’s equipment performs DLCO tests using real-time gas analysis and that is what I am used to.
I think that each approach has some benefits and some weaknesses but I’ll start first with a bit of background. When the single-breath DLCO test was standardized in more-or-less it’s current form in the mid-1950’s, the only gas analyzers available at that time were slow. They required relatively large samples of gas (>100 ml) and took over 10 seconds to settle to their final reading. The only way to perform the DLCO test was to capture a sample of alveolar gas and then analyze the entire sample.
In a very simplified view, a sample balloon DLCO system works something like this:
Inhalation to TLC
Late in 2012 the Global Lung Function Initiative (GLFI) released their reference equations for spirometry. Although not without some criticism this was an important step towards the development of a single spirometry reference equation that can be used by PFT Labs worldwide. The GLFI recently announced that they were accepting data for their TLCO Task Force. This is project similar to what was done for spirometry, and is intended to create a set of reference equations for TLCO (DLCO) that is applicable to all ages and ethnicities.
The GLFI Task Force is actively seeking test results on representative and “healthy” populations from labs anywhere in the world and in particular results from young and elderly individuals. They are looking for data sets from a minimum of 100 (or 150, there is some confusion about the minimum number in the Task Force’s own documentation) individuals. PFT Labs that wish to participate will need to provide information about each subject’s age, height, weight, gender, ethnicity and health status. Patient results will be de-identified before submission to protect patient privacy. Labs will also need to provide information about the test systems (brand and model number) and software (version number) used to perform the tests.
Please visit the GLFI TLCO Task Force web page if you have any interest in this project.
I applaud this project and look forward to seeing their results. The current DLCO reference equations have severe limitations both in the number of subjects and in the range of ethnicities included in the studies and the GLFI TLCO project should go a long way towards clearing up the many of the known inconsistencies.
The lungs are the gas exchange organ of the body. The mechanical aspects of the lung, which do of course have a bearing on gas exchange, can be assessed by spirometry and lung volume tests but for a complete assessment of an individual’s lung function a diffusing capacity test (DLCO) must be performed as well. The actual gas exchange rate at any moment can be highly variable and depends on a number of factors such as cardiac output, pulmonary capillary blood volume and ventilation-perfusion matching that are difficult to measure. For this reason the diffusing capacity test, more so perhaps than any other pulmonary function test, must be performed in a highly standardized way in order to produce results that can be meaningfully trended over time and meaningfully compared to other individuals.
Accurate diffusing capacity results therefore depend on attention to details such as inspiratory time, inspiratory capacity, breath-holding time, washout volume and alveolar sample size. Even when these values are essentially identical results can still vary dramatically from test to test. For this reason my PFT lab’s policy is to perform a minimum of two DLCO tests and if the results aren’t reproducible then a third test and possibly a fourth test. Whenever possible the closest (not the highest) results from two good quality tests are averaged and reported. We think that this approach gives is the best way to get accurate and reproducible DLCO test results from our patients.
This may give my lab DLCO results that are adequate for trending but how do we know when they are normal? Like everybody else we have to rely on a reference equation generated from a study of presumably normal individuals. Selecting the proper reference equation continues to be an ongoing problem. I have been able to find fourteen different DLCO reference equations that appear to be in more-or-less common use. Even after comparing them however, I am not sure the selection process is any clearer or easier.