Category Archives: Reference Equations

What’s normal about FEV1 and how much does ethnicity matter?

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When it comes to spirometry, it’s really all about FEV1. FVC and the FEV1/FVC ratio are also important of course, but because FVC is more likely to be underestimated than FEV1 they are less reliable.

Changes in FEV1 are critical in monitoring airway disease. The recent ATS guidelines on Occupational Spirometry indicate that a 15% decrease (adjusted for changes in age) is significant and cause for concern. For diagnosing airways disease however, it is important to know what a normal FEV1 is.

I have been able to find twenty-four different reference equations for FEV1. That’s good in one sense but that quantity also makes it that much more difficult to determine which reference equations should be used. When I graph results it often becomes more apparent what the equations are trying to tell us but in this case I came away a bit more confused instead.

Female FEV1 165 cm non-clustered

Male FEV1 175 cm Age non clustered

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How should predicted TLC and RV be derived?

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The ATS-ERS standards on lung volume measurements says that measured TLC and RV can be calculated either by

RV = FRC – ERV then TLC = RV + SVC

or by

TLC = FRC + IC then RV = TLC – SVC

with the preference going to the first method. Strictly speaking, given the same FRC and SVC measurements either method is going to end up with exactly the same calculated TLC and RV values. Conceptually speaking I believe that TLC = FRC + IC is a more relevant way to think about TLC but this is only because I think that patients find it easier to perform a quality IC maneuver than a quality ERV maneuver.

A while back I found out that the predicted TLC in my lab’s test systems was being derived from the predicted RV from one set of equations and the predicted FVC from another set of equations (i.e. predicted TLC = predicted RV + predicted FVC). This is likely done so that there will be no discrepancy between the predicted FVC and predicted SVC on reports. I am not sure this is the correct decision since SVC does tend to be slightly larger that FVC but the difference is admittedly small (<1%) in healthy subjects so it is not likely to be significant.

Does it matter, however, for predicted TLC and RV which value’s reference equation you start with and which FVC reference equation you use with them? 

There are, of course, many different reference equations for lung volumes and spirometry, but to keep this simple I will choose the ones that I think are the most common and most relevant. For a 50 year old, 175 cm Caucasian male therefore, the predicted lung volumes look like this:

Equation: TLC FRC RV SVC
Quanjer 6.90 3.42 2.16 4.74
Crapo 6.74 3.60 1.98 4.76

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The GLFI TLCO Task Force is open for business

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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.

What’s normal about DLCO?

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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.

DLCO_Male_175cm_80kg

DLCO_Female_165cm_60kg

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What’s normal about RV and what does this have to do with TLC?

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A physician associated with my PFT lab has become an investigator for a device study intended for patients with severe COPD. One of the major criteria for patients to be able to enroll in this study is a severely elevated Residual Volume (RV). Patients who have met this criteria at other PFT labs in New England have been referred to this study but when they have been re-tested in my lab their Residual Volumes are coming out lower and almost none of these patient have met this criteria. We have been asked why this is the case because they are now having difficulty finding patients that qualify for the study.

We have not been given access to the original PFT reports for these patients and have not been able to actually compare results on a case by case basis. For this reason we can only offer two possible reasons. First, that my lab may not be using the same reference equations for RV that other labs are. Second, that these patient’s RV’s may have been overestimated at other labs because of errors in testing.

To compare predicted RV’s I was able to find a dozen different reference equations for RV in adult males and females. These equations are mostly for Caucasian populations, but I was also able to find at least one reference equation each for Black, Asian, Indian, Iranian and Brazilian populations as well.

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GLFI and the FVC, FEV1 and FEV1/FVC Ratio

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The Global Lung Function Initiative (GLFI) was established by the European Respiratory Society in 2008 with the goal of establishing a truly worldwide set of reference equations for spirometry. Its results were released in the December 2012 issue of the European Respiratory Journal. Although the reference equations presently apply only to Caucasians, African-Americans and northern and southern Asians, it will likely be updated with Hispanic, African and Polynesian data within the next couple of years.

This has been a massive undertaking involving spirometry data from 72 different testing centers in 33 countries. The data has been subjected to rigorous quality control and an extensive, sophisticated statistical analysis and will likely become the standard reference equation set for spirometry testing in Pulmonary Function labs around the world.

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Open-access on-line medical journals

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I have been researching different pulmonary function topics for quite a few years. The medical libraries I’ve frequented were, of course, originally all paper-based and to be able to find an article the library or one of the department’s physicians had to subscribe to the journal in question. In the last fifteen years we have all seen an explosion in on-line publishing and it has become much easier to research articles. I vigorously applaud the pulmonary medicine journals (Chest, American Journal of Respiratory and Critical Care Medicine, European Respiratory Journal, Journal of Applied Physiology, Thorax) for having opened part or all of their archives to anybody who wants to search and download articles.

There are a number of other journals, however, that remain entirely behind paywalls. I was reminded of this recently while looking for an article on diffusing capacity from the 1970’s only to find that it would cost me $31 to access it (and then only for 24 hours). Although strictly speaking this does not prevent anyone from accessing these articles, anybody who does has to have deep pockets and this is acting as a significant barrier to the ability of individuals and institutions to obtain and to share information.

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Height and arm-span

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The PFT Lab I am associated with has been making a point of having the technicians re-measure patient height with each visit. Part of the reason for this is that several years ago the medical assistants in the pulmonary outpatient clinic were tasked with obtaining patient heights, weights and blood pressures. For a period of time the technicians used these heights when entering the patient demographic information but it was soon noticed that patient heights often changed by several inches from visit to visit. For this reason we have asked the technicians to re-measure patient height instead.

One possible cause for the fluctuation in heights was that the medical assistants were measuring patient height using the height rod attached to the scale while also taking their weight. The PFT Lab has wall-mounted stadiometers in or near all of the lab’s testing rooms so that patient height can be taken with their back against the wall rather than free-standing.

Another reason to regularly re-measure patient height is that the lab’s population has a significant number of patients that have routinely been seen by the lab and the pulmonary physicians for years. The lab’s patient and results database now goes back over twenty years and patients that were seen 15 and 20 years ago have been referred again for pulmonary function testing and their height has changed in the meantime.

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Peak VO2 and low body weight

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The PFT Lab I am associated with performs cardiopulmonary exercise tests for pre-op cardiothoracic surgery patients with lung cancer. Surgeons have to make a decision to operate or not based at least in part on the amount of function they think will remain after a lung resection and this depends on which and how many lobes are involved. This calculation is done by taking a percentage based on the amount of lung tissue that will be lost which is weighted using ventilation-perfusion scan results off the baseline DLCO and vital capacity. When the result is inconclusive or there are other medical factors that can affect a patient’s prognosis the results from a CPET can help with the surgeon’s decision.

The criteria that has been most often cited as an indicator of acceptable surgical risk is a peak VO2 greater than 15 ml/kg/min. About ten years ago we encountered a patient with a significantly low body weight. His max VO2 was about 16 ml/kg/min which appeared to make him a good candidate for surgery but his actual maximum oxygen consumption in LPM was 45% of predicted. This discrepancy was due to the fact that his BMI was about 14. We re-calculated what his peak VO2 would have been if his body weight had been normal and that was less than 10 ml/kg/min. For this reason our recommendation at that time was that the patient was a poor candidate for surgery. Continue reading →

Evaluating spirometry predicted equations for the elderly

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I’ve mentioned previously that the PFT Lab I am associated with recently went through a major hardware and software update. As part of this update we decided to change spirometry predicted equations to NHANESIII. The lab has used the Morris equations for at least the last 25 years and this has caused us to revisit a number of issues associated with interpretation of results, one of which is age.

The software update included the NHANESIII equation set but when we selected it we found that the software would not calculate predicted values for patients over the age of 80. The manufacturer said that this was because that was as far as the age range went in the original NHANESIII study and for this reason they could not extend it. Furthermore, their recommendation was to use the Crapo or Knudsen equations for ages above 80 because they were “more linear”. Continue reading →