Author: Richard Johnston

Although the authors of the Global Lung Function Initiative (GLFI) study acknowledge the effect of height on their reference equations the range and distribution of heights in its study populations was not included in the report. This was a similar problem for the NHANESIII reference equations since the height range was never reported within the text of the original report however it did include scatter graphs showing the range of heights. These graphs imply the height range was 162 to 194 cm (64” to 76”) for caucasian males and 145 to 180 cm (57” to 71”) for caucasian females. Using the extremes of these height ranges it is interesting to see how the GLFI reference equations compare to the NHANESIII reference equations.

Not unexpectedly there are pronounced differences between between the NHANESIII reference equations and the GLFI reference equations however these differences are not the same for short and for tall individuals and in fact tend to be more or less opposite.

For short individuals, both male and female, the GLFI reference equations predict a lower FVC and FEV1 than do the NHANESIII reference equations earlier in life but a higher FVC and FEV1 later in life. For FVC, the NHANESIII and GLFI values intersect at about age 70 in females and about age 75 in males. For FEV1 the intersection is about age 53 in females and about age 43 in males.

Tall individuals, also both male and female, show the opposite pattern. The GLFI reference equations predict a higher FVC and FEV1 than do the NHANESIII reference equations early in life and a lower FVC and FEV1 later in life. For FVC NHANESIII and GLFI intersect at about age 45 for females and about age 47 for males. For FEV1 the intersection is about age 45 for females and about age 50 for males.

 Airway obstruction is more commonly diagnosed with the FEV1/FVC ratio than with just the FEV1. The predicted GLFI FEV1/FVC ratio is higher than the NHANESIII FEV1/FVC ratio for both sexes, heights and almost all ages. Depending on the technique used to assess FEV1/FVC ratio normalacy there is likely to be a difference in the number of patients who meet the criteria for airway obstruction. 

Despite the fact that the predicted GLFI FEV1/FVC ratio is higher, except for the very shortest individuals the lower limit of normal for the FEV1/FVC ratio tends to be lower than the NHANESIII LLN. When the LLN is used as the primary indicator of airway obstruction then there will likely be an overall decrease in the number of patient’s given that diagnosis.

Use of the LLN is not universal however, and there are still many PFT labs that use a fixed percentage of the predicted FEV1/FVC ratio instead. In this case regardless of where the bar has been set, there is likely to be an increase in patients diagnosed with airway obstruction.

(I will note in passing that the difference between the use of the lower limit of normal and a fixed percentage should not considered to be an argument for or against either approach. There has been substantial momentum towards the use of LLN and I understand the argument in its favor, but it is still a primarily a statistical approach with a limited amount of verification in terms of patient outcomes.)

I expect the GLFI reference equations to become the worldwide standard for all pulmonary function labs. I would appreciate having a better understanding of the lower and upper limits for height in the GLFI data set, however. When my PFT lab went through its hardware and software upgrade a year ago, we had an issue with the age range in the reference equations supplied with the software. There are, however, no particular limits on the height that can be entered for a patient and this particular aspect of reference equations seems seems to be frequently overlooked. The number of patients seen in my PFT lab that are outside the height range I’ve gotten from the NHANESIII study are small but they do exist and it would seem to be a good idea to know the credible height range for any given set of reference equations.

References:

Hankinson JL, Odencrantz JR, Fedan KB. Spirometric Reference Values from a sample of the general U.S. Population. Am J Respir Crit Care Med 1999; 159: 179-187.

Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Enright PL. Hankinson JL, Ip MS, Zheng J, Stocks J. Multi-ethnic reference values for spirometry for the 3-95 year age range: the global lung function 2012 equations. Eur Respir J 2012; 40: 1324–1343.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

I was reviewing a cardiopulmonary exercise test (CPET) recently. The test was part of a pre-op workup for a patient with lung cancer who also had a diagnosis of COPD. I had looked at the spirometry results first (we always do spirometry pre- and post-exercise) and seeing that the patient had severe airway obstruction (FEV1 < 50% of predicted) assumed the review would be relatively straightforward. I then saw just one exercise test value and knew immediately that this wasn’t going to be an ordinary test. That test value was the PETCO2 at anaerobic threshold, which happened to be 40.

There are a number of CO2-related values that are useful when assessing exercise test results. Although End-tidal CO2 (ETCO2) is not a quantitative measurement in the same sense that minute ventilation or oxygen consumption is, it is still able to provide a lot of useful information about ventilatory efficiency and disease states.

ETCO2 is related in various degrees to tidal volume, respiratory rate, the deadspace to tidal volume ratio (Vd/Vt) and CO2 production. There is a correlation between PETCO2 and both alveolar CO2 (PACO2) and arterial CO2 (PaCO2) however the correspondance is far from exact or predictable. Alveolar CO2 fluctuates cyclically with ventilation and since Vd/Vt is never zero PETCO2 is always higher than the average PACO2. Numerous investigators have developed algorithms that correlate PETCO2 with arterial CO2 but during exercise PETCO2 can be well below PaCO2 because of ventilatory inefficiency or it increase well above PaCO2 because it can become dominated by mixed-venous PCO2.

When there is a mismatch between ventilation and perfusion, ventilation has to increase in order to maintain the same level of gas exchange. Ventilation-perfusion mismatching and an exaggerated ventilatory response to exercise is a common features in diseases as different as COPD, pulmonary hypertension and ventricular failure. When ventilation is increased relative to CO2 production during exercise this fact shows up in the Ve-VCO2 slope, the mixed-expired CO2 (PECO2) and the PETCO2.

PETCO2 should be evaluated in terms of its maximum observed value and in its overall pattern during and following exercise. The maximum PETCO2 usually occurs at or near anaerobic threshold and the lower limit of normal is around 35 mm Hg. The maximum PETCO2 is reduced below 35 in both cardiac and pulmonary disease and the amount of reduction tends to correlate well with the severity of the disease.

This by itself is what told me that despite the reduced FEV1 and the diagnosis of COPD, with a PETCO2 of 40 at anaerobic threshold the patient probably had normal gas exchange. We do not routinely do diffusion capacity testing as part of a cardiopulmonary exercise test so that part will have to remain speculative. When the Ve-VCO2 slope was calculated however, it was 28, which is well within normal limits. Most COPD patients we see for CPETs have a PETCO2 of 30 or less and Ve-VCO2 slopes greater than 40.

The overall pattern of the patient’s PETCO2 during exercise was also wrong for COPD. The PETCO2 pattern that normal patients show during a CPET is to start off with a relatively low PETCO2. The PETCO2 then increases to its maximum value (usually at AT) and then decreases to peak exercise.

Patients with cardiac disease show a similar pattern to normal patients with the exception that the maximum PETCO2 is reduced below 35 and the degree of reduction correlates well with the NYHA stage of cardiac disease.

Patients with pulmonary hypertension however, show a distinctly different pattern where PETCO2 declines throughout testing and if anaerobic threshold is attained, the PETCO2 at that time is not the maximum PETCO2.

COPD patients also tend to have distinct pattern, that is pretty much the opposite of pulmonary hypertension. For COPD patients PETCO2 tends to rise throughout testing. Again if there is an anaerobic threshold, the PETCO2 at that time also tends not to be the maximum PETCO2.

The patient had a distinctly normal PETCO2 pattern and despite the low FEV1 and some dynamic hyperinflation (end-expiratory lung volume increased by 0.45 L) did not end up being limited by their ventilation (maximum minute ventilation was 70% of predicted and their Vt/IC ratio was 0.80). The patient stopped exercise because of leg fatigue but had reached 98% of their predicted maximum heart rate. The final summary was that there was a primarily cardiovascular limitation, most likely due to a low stroke volume (elevated chronotropic index and reduced maximum O2 pulse).

Now, having said all this, in this case what the normal PETCO2 at AT and normal PETCO pattern during exercise did was to alert us to the fact the patient was not going to have CPET typical of a patient with pure COPD. COPD patients tend to have both a pulmonary mechanical limitation because of their airway obstruction and a pulmonary vascular (gas exchange) limitation and it’s usually matter of determining which these two factors is the primary limitation. For this patient whatever gas exchange limitation they had was in a distant second place. This would have shown up eventually from the Ve-VCO2 slope if nothing else, but the PETCO2 at AT told me this immediately.

PETCO2 is most useful as an indicator. You can’t take the PETCO2 at AT or the PETCO2 pattern during exercise and predict what the CO2 production, the Vd/Vt or the minute ventilation are going to be. PETCO2 however, is easy to measure and to monitor during exercise and can alert you to a potential diagnosis well before the final results are available.

References:

Bussoti M, Magri D, Previtali E, Farina S, Torri A, Matturri M, Agostini P. End-tidal pressure of CO2 and exercise performance in healthy subjects. Eur J Appl Physiol 2008; DOI 10.1007/s00421-008-0773-z

Chambers JB, Kiff PJ, Gardner WN, Jackson G, Bass C. Value of measuring end tidal partial pressure of carbon dioxide as an adjunct to treadmill exercise testing. Brit Med J 1988; 296: 1281-1285.

Hansen JE, Ulubay G, Chow BF, Sun X-G, Wasserman K. Mixed-expired and end-tidal CO2 distinguishes between ventilation and perfusion defects during exercise testing in patients with lung and heart diseases. Chest 2007; 132: 977-983.

Liu Z, vargas F, Stansbury D, Sasse SA, Light RW. Comparison o the end-tidal arterial PCO2 gradient during exercise in normal subjects and in patients with severe COPD. Chest 1995; 107: 1218-1224.

Matsumoto A, Itoh H, Eto Y, Kobayashi T, Kato M, Omata M, Watanabe H, Kato K, Momomura S. End-tidal CO2 pressure decreases during exercise in cardiac patients. Association with severity of heart failure and cardiac output reserve. J Amer Coll Card 2000; (36)1: 242-249.

Myers J, Gujja P, Neelagaru S, Hus L, Vittorio T, Jackson-Nelson T, Burkhoff D. End-tidal CO2 pressure and cardiac performance during exercise in heart failure. Med Sci Sports Exerc 2009; 41(1): 18-24.

Yasunobu Y, Oudiz RJ, Sun X-G, Hansen JE, Wasserman K. End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension. Chest 2005; 127: 1637-1646.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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.

The reference equations are quite complex, if for no other reason than that they cover an age range that encompasses young children to the elderly (age 3-95). I have a limited background in statistics and find it difficult to understand how the various factors in the equations were developed and how they work together. The best I can do is to compare the GLFI predicted values to the reference equation my lab is presently using, NHANESIII. Starting with adult male and female Caucasians of average height, there are several apparent differences.

It is evident that the GLFI reference equations describe a more complex relationship between age and spirometry values than does NHANESIII. The NHANESIII reference equations are simplistic in that they are regularly curvilinear for FVC and FEV1 and show an accelerating decline in these values with increasing age. Even more so for the FEV1/FVC ratio that is entirely linear and shows a steady decline with age. In comparison, the GLFI reference equations for FVC shows that the maximum FVC volume for both males and females is attained in their mid-20’s whereas NHANESIII shows it peaking around age 20. Similar to NHANESIII the GLFI shows an accelerating decrease in FVC up to middle age, but then shows a period of linear decrease up to about age 75 and finally a decelerating rate of change thereafter. For FEV1, the GLFI reference equations show a similar, although somewhat subtler pattern to that of FVC and like NHANESIII, FEV1 peaks around age 20. For the FEV1/FVC ratio, both NHANESIII and GLFI show approximately the same trajectory up until middle-age, when the GLFI starts to decrease less rapidly than NHANESIII.

 

The practical consequences of switching from NHANESIII to GLFI would be that more patients would be considered normal. This is partly because the predicted FVC and FEV1 values tend to be lower for GLFI than they do for NHANESIII. It is also because the lower limit of normal (LLN) for GLFI is lower both in an absolute sense and because there is a larger spread between the predicted values and the LLN. This larger spread of LLN is particularly true of the FEV1/FVC ratio because even though the predicted ratio is higher for the elderly than it is for NHANESIII, the LLN is strikingly lower.

One implication of this would certainly be that in particular fewer elderly patient would be diagnosed with obstructive lung disease. It also implies that airway obstruction is less prevalent in the general population than currently thought. Having said that I continue to have reservations about the use of LLN primarily because I think it sets the bar too low but since it appears that LLN is well on its way towards becoming a worldwide standard, I will probably just have to live with this.

I don’t think there is much doubt that the GLFI reference equations will become the worldwide standard for spirometry testing. Creating the GLFI equations was a monumental undertaking requiring a data set of over 97,000 spirometry records from around the world that were subjected to rigorous quality control and statistical analysis. In contrast, the prior gold standard for spirometry testing, the NHANESIII study, contained only 7429 spirometry records, primarily from an American population.

The GLFI data set will no doubt be mined by researchers and statisticians for some time to come. I think one of the most important contributions the GLFI makes is that what it is telling us about lung function and age is much more likely to be true than any prior study has been able to.

Although the GLFI sets a new standard for spirometry reference equations, it remains an evolving process. At the very least it still needs to be fleshed out with data from more ethnicities before it can be considered to be in any way complete. Along those lines, I would like to see more guidelines about determining ethnicity given that ethnicity is too often a matter of opinion rather than physiological fact. I would also like to see more longitudinal studies that attempt to verify how well the LLN actually matches reality.

You can download Excel spreadsheets and Windows software for exploring the GLFI equations from the GLFI website.

References:

Hankinson JL, Odencrantz JR, Fedan KB. Spirometric Reference Values from a sample of the general U.S. Population. Am J Respir Crit Care Med 1999; 159: 179-187.

Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Enright PL. Hankinson JL, Ip MS, Zheng J, Stocks J. Multi-ethnic reference values for spirometry for the 3-95 year age range: the global lung function 2012 equations. Eur Respir J 2012; 40: 1324–1343.

It’s always fascinating how a simple problem can blossom into something much more complicated. Ninety-five percent of the time when we need to report post test results for spirometry they are for post-bronchodilator. The remaining times they are for supine or post-exercise spirometry. At least once or twice a month however, we need to report two post results, not just one and this is where we run into problems.

The most common scenario for this is when we need to report a baseline result and then both a post-exercise result and then a post-bronchodilator result. We need to do this when a patient bronchospasms during or following an exercise test and we find need to give them a bronchodilator after performing the post-exercise spirometry. Less commonly we are occasionally requested to perform both supine and post-bronchodilator spirometry as part of the same visit. Whenever either of these situations occurs we need to perform a number of work-arounds that end up taking extra time and effort.

The problems start in the spirometry test module. In post test mode it is possible to put different labels (“Albuterol”, “Combivent”, “Supine”, “Exercise”) on post spirometry test results. This means that each post test result can have a different label but it is only possible to select one and only one result (which can be a composite but can only have one label) to be reported. This problem is reflected in the Reports module of our lab software which does not permit more than one post result to be placed on a report.

These limitations mean that we need to create two “visits” in the lab database and two reports in order to capture the two post results. This also means that whichever post result is performed as part of the second “visit” there is no baseline to compare it to and that when interpreted changes from baseline have to be calculated manually.

If all we had to deal with was two reports this wouldn’t be a real problem. It gets more complicated very quickly. There is an intimate connection between our hospital’s appointment scheduling system, the hospital’s billing system for PFTs, the physician billing system for PFT interpretations and reports. There is a one-to-one relationship between appointments, bills and reports. So in order to get two reports uploaded into the hospital’s computer system there has to be two appointments. Because there are two appointments there are two sets of bills (hospital and professional, one for each appointment) but we can’t bill for supine or post-exercise spirometry. So only one report can have spirometry with bronchodilator billed and the second report can’t be billed at all which means we have to manually generate an exception for the hospital and professional billing systems. It also means that if an additional post test is unexpectedly “added-on” for any reason that we need to go back and create another appointment for the patient.

We’re not going to stop performing combinations of supine, post-exercise and post-bronchodilator spirometry simply because we can’t bill for them and because of the problems they cause in dealing with reports, appointments and billing. This is just part of taking care of our patients. It does mean that the lab staff need to pay close attention when making appointments and billing for any patient testing that will have two post spirometry results however.

These procedural problems could be solved right where they started, in our lab software’s spirometry and reporting modules. If multiple post spirometry results could be selected and reported then there would be no need for the appointment and billing work-arounds. I can think of several different ways to select multiple post results within the spirometry test module without altering our lab database so this is the easy part, relatively speaking. Reports are a far more complicated problem.

When thinking about reporting multiple post results in the same report I can think of of two different approaches. First, increase the width or number of columns in the spirometry module of the report so that the baseline and two sets of post results can be reported.

 

The second approach would be to duplicate the spirometry report module so that the baseline and first post results appear in the first table, and the second post results appear in the second module.

Reports remain problematic however, because when designing a report with our lab software you are required to place the report elements in specific locations on each page. We have created a single report that can contain all possible tests and all possible results that we perform but this report is 12 pages long and for almost all patients there are a lot of empty result modules and it is very confusing and difficult to read. We save this report for those times we need to provide results to researchers. For everybody else we have created another eight different report formats that are much shorter and contain the most common combinations of tests we perform. Even so, no report is less than three pages long and a few are as much as five pages long. Given the current state of the reporting software we would have to add at least a couple new report formats in order to handle multiple post spirometry results in a single report.

I am not happy with our reporting software. This static approach to report formatting is very cumbersome because when we need to change even just one element on the report then nine different report formats need to be individually updated. Since it is not possible for the lab software to select the appropriate report format automatically this also means that report formats have to be manually selected and if the wrong format is selected then results will likely be missing from the printed report.

The static report formatting approach, where the report elements have to be placed in specific locations on a page, is not unique to our equipment manufacturer’s lab software and in fact, it appears to be the most common approach and I just don’t get it.

A large part of the reason I don’t get it is that I remember 15 years ago when the DOS version of our lab’s software used dynamic report formatting. A report was made up of modules, one module for each possible report element (demographics, spirometry, DLCO, graphs etc). Once each module had been customized and the order of the modules specified, that was it, you were done. There was only one report format so you only had to make changes once. When a report was printed then only the tests the patient performed would appear on the report which also meant the length of the report changed as well. Reports were always simple and readable with no blank spaces.

I guess I could understand the static approach if you wanted to create a standardized single-page spirometry report but once you have a PFT lab that provides many different tests in many different combinations then either you have to create a single, hard to read report that contains everything including the kitchen sink or you have to create and maintain many different report formats. Like I said, I don’t get it. Unfortunately our equipment manufacturer “improved” our reports when we went to the first Windows version of our lab software and we lost this simple functionality. If our lab equipment manufacturer ever goes back to dynamic report formatting then printing multiple post spirometry results will be easy and straightforward.

In a sense this problem really starts with the assumption that there will never be a need to select and report more than one post spirometry result. This is just not true and we’ve had to develop a complicated set of work-arounds to get it to happen. I suspect that we are not alone in this but I also suspect that hardly anybody considers this a big enough problem to bother really fixing it and that’s too bad.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Over forty years ago when I started to learn about pulmonary function testing I was taught about the nuts and bolts of the tests, not where the tests came from or how they came into existence. Spirometry and the FVC, FEV1 and FEV1/FVC ratio have always appeared to be the core elements of pulmonary function testing and seemed most likely to have been scratched on the wall of the first paleolithic PFT lab cave. I have been reviewing a lot of older research papers lately, including several historical reviews, and was quite surprised to find out how recent both FEV1 and the FEV1/FVC ratio really are.

The first version of the modern spirometer (a counter-weighted volume displacement water seal spirometer) was developed by John Hutchinson in England around 1844. He performed vital capacity measurements on over 3000 people and in 1846 published a paper where he showed (among other things) the linear relationship of vital capacity to height. Different versions of Hutchinson’s spirometer were developed by other researchers in the following decades but even through the 1920’s the only measurement that was ever made with a spirometer remained just the vital capacity.

Part of the reason for this has to do with the spirometers of that time. Spirometer bells were usually very heavy and required an equally heavy counterweight. The tubing and the mouthpiece leading into the spirometer was often quite narrow. The combined effects of inertia and resistance made these very poor instruments for measuring expiratory flow. These technology limitations however, also reflect the expectations at that time. Even though spirometers were often equipped with a kymograph drum (first one in 1866) and a lighter spirometer bell could have been made at almost any time the entire concept of measuring a timed vital capacity or of measuring expiratory flow was not on anybody’s horizon.

The first instrument capable of measuring expiratory flow with any fidelity was the pneumotachograph which was developed in the mid-1920’s by Alfred Fleisch. This started to lay the ground work for an appreciation for the importance of expiratory flows and by the 1930’s some researchers had started to note that patients with emphysema took longer to blow their air out than patients with normal lungs. The length of time a patient took to blow out their vital capacity was even proposed as an index of lung disease but at that time the primary attention of most researchers and clinicians was on the Maximum Breathing Capacity (MBC) which was first described in 1933.

Numerous researchers performed the MBC test in both normal subjects and in patients with lung disease over the next several decades and were able to show that there was a relationship between a reduced MBC and lung disease. The range of published normal values for MBC was quite broad however, so one important side effect was that the ability of spirometers to accurately measure MBC (and expiratory flow rates) became important and the concept of spirometer frequency response became much better appreciated.

The MBC test was very strenuous (it was originally performed for 30 seconds) and clinicians were unhappy that most patients were unable to perform the more than a couple times and that training was usually required for the MBC to be performed correctly at all. There was also a certain recognition that a reduced MBC was relatively non-specific.

In 1947, a French researcher, Robert Tiffeneau published the first paper where the FEV1 (which he called the “capacité pulmonaire utilisable à l’effort” or CPUE) was proposed as a replacement for the MBC test. The choice of a 1 second period for a forced exhalation was to a large extent arbitrary and was based on Tiffeneau’s observation that during exercise patients breathed at around 30 breaths per minute so a 1-second maximal exhalation should be able to approximate a patient’s maximum exercise ventilation.

Tiffeneau’s work was not well known outside of France but in 1951 Edward Gaensler of Boston, Massachusetts published a much wider-read paper on the timed vital capacity and included the concept of expressing the FEV as a percentage of the FVC. Research continued on the MBC but an increasingly larger number of researchers began to study the timed vital capacity.

A number of forced vital capacity measurements were proposed during this time by various researchers and include the FEF200-1200 (mean expiratory flow between 0.2 and 1.2 L of the FVC), the FEF25-75 (AKA MMEF, which is the mean expiratory flow between 25% and 75% of the FVC), FEV 0.5 sec, FEV 0.75 sec, the FEV 2.0 and others. A variety of ways of describing the same measurements quickly developed and in 1956 the British Thoracic Society made its recommendations on terminology and the FEV1 and FEV1/FVC ratio as we know it came into being.

I’ve known that Hutchinson developed his spirometer in the 1840’s for quite a while and had always assumed that that the FEV1 and FEV1/FVC ratio dated from that period as well (I mean it’s obvious, isn’t it?) but when compared to diffusing capacity (Krogh, 1910) and lung volumes (Davy, 1800) they are relative newcomers.

As a footnote I will mention that even after the FEV1 became an accepted (and critical) component of the FVC it took a while for spirometer technology to truly catch up. When I started working in a Pulmonary Function lab in the early 1970’s with an almost brand-new testing system it was equipped with a counter-weighted water seal spirometer with a stainless steel bell. The kymograph pen was attached to the counterweight and I remember frequently seeing the chain between the bell and the counterweight go slack during the FVC maneuver. This meant the counterweight and more importantly, the kymograph pen, was not keeping up with the spirometer bell and that the FEV1 I was measuring on the graph paper was being underestimated. That lab didn’t get its first direct-recording spirometer (pen attached to the bell) or pneumotachograph until 1980.

References:

Freedman S. Assessment of airway obstruction. How the subject developed. Proc Royal Soc Med 1971; 64: 1229-1232.

Kingesepp PH. Alfred Fleisch (1892-1973): Professor of physiology at the University of Tartu, Estonia. J Med Biog 2011; 19(1): 34-37.

Yernault JC. The birth and development of the forced expiratory manoeuvre: a tribute to Robert Tiffeneau (1910-1961). Eur Resp J 1997; 10: 2704-2710.  

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

I’ve had some concerns for a while now about how the CO and CH4 concentrations are being calculated from the DLCO analyzer calibration zero offsets and gains on our test systems. For this reason I’ve been looking carefully at all of the raw data from our DLCO tests and today I came across an oddball test result. There are several reason why this is probably not the best example for this particular problem that I could come up with but it illustrates an important point and it’s in front of me so I’ll go with it.

In order to use the output from a gas analyzer you need to know the zero offset and the gain of the signal. Presumably the analyzer remains stable enough between the time it was calibrated and the time it is used for the zero offset and gain to be meaningful. When looking at the calibration data I’ve noticed that some of our test systems show relatively large changes in zero offset from day to day. These changes are still within the operating limits of the analyzer so no red flags have gone up over this. The test systems and analyzers are turned off over night so in order to see if the analyzers go through these kind of changes during a normal day I once did a series of calibrations each separated by five or ten minutes on one of the more suspect testing systems. What I saw was that although there were small changes from calibration to calibration, I didn’t see anywhere near the changes I’ve seen from day to day which at least implied that the analyzer remained reasonably stable during a given day.

Today a patient’s report came across my desk and as usual I took a look at the raw test results. What I saw was that two out of three of the DLCO tests had been performed with the correct inspired volume but that the one with a much lower inspired volume had a much larger VA and DLCO when compared to the other results. This got me scratching my head since the patient has severe COPD and that usually means that a lower inspired volume leads to a lower DLCO and VA. When I noticed the analyzer signals during the breath-hold period that’s when I could see right away why the results had been overestimated.

Here’s the test with the low inspired volume:

 

Here’s a test from the same patient with the proper inspired volume:

 

In our test systems the DLCO analyzer continues to sample the inspired gas during the breath-holding period. On the graphs this is normalized using the calibration zero offset and gain to 100% rather than to a specific concentration (it doesn’t matter what values you use because it’s the ratios of concentrations that matters not the actual concentrations). In the oddball test the inspired gases show up as being around 85% not 100%. You will also notice that in this test the exhaled CO and CH4 concentrations are significantly lower than in the other tests.

My take on this (and of course the manufacturer’s technical staff may well disagree) was that there was an abrupt decrease in the DLCO gas analyzer’s zero offset. When the zero offset decreases, even if the gain remains unchanged, the analyzer’s signal output will be reduced. This is what I think caused the inspired gas concentrations to be reduced.

Although the DLCO gas analyzer goes through a pre-test check (not a calibration), either the change in zero offset was still within specifications or the zero offset changed after the pre-test check. If the analyzer’s signal was reduced then the exhaled CH4 and CO concentrations will also be reduced. Since VA is calculated from the inspired volume and the change in CH4, despite the fact that the inspired volume was low the calculated VA is elevated. DLCO is in turn calculated from the VA and the change in CO and since the VA was elevated and the exhaled CO was reduced the DLCO is going to be higher.

The oddball test was the second of three tests. The first and the third test both had the proper inspired volume and the inspired gases were at 100% so whatever the problem was, it came and went quickly. It’s possible there was a voltage surge or dropout although I would have expected the power supply for the analyzer to handle these things. This is one of the reasons that makes this test a poor example. What it does illustrate however, is that (once again) the test with the highest results is not always the test that should be reported. It also shows the need to remain vigilant about even small details in test results.

I think that inspired volume is the most important quality indicator of DLCO tests. There is more than sufficient reason to be suspicious when a DLCO test with a low inspired volume has a higher result than a test with the proper inspired volume. Although I also tend to think that a DLCO test with a higher VA is probably more accurate than a test with a low VA in this case I think the elevated VA was due to an analyzer error and the clue to that error was the low inspired gas concentration.

This is likely a moderately unusual error at least in terms of its magnitude. It remains unclear to me just how common or uncommon this kind of problem actually is. I suspect that on a much smaller scale it is probably a common occurrence since that’s just the nature of analog electronics. It’s taken me some time but I’ve learned from our equipment manufacturer that the software for our test system uses the zero offset and gain from the last “real” calibration to calculate exhaled CH4 and CO. Even though the DLCO analyzer goes through a pre-test check, the results of check are compared to the normal operating range of the analyzer and not to the last calibration. Since the results from the pre-test analyzer check are not saved or stored in any way this means that (at least presently) it’s not possible to determine what changes in zero offset and gain routinely occur during the course of a given day.

[Warning, rant ahead!]

In a more general sense I am concerned that the details of how our pulmonary function test equipment actually gets from physical measurement to numerical results has become, if not exactly hidden, at least difficult to get at. I don’t necessarily blame the equipment manufacturers because if more people in our field asked these kinds of questions they would likely be more forthcoming with answers. Having said that I don’t think it is realized just how much of the accuracy we take for granted in the test systems we use every day is based on proprietary, and therefore opaque, hardware and software processes. I wince every time I read a research paper and see that critical results came from “test system model 123 of manufacturer X” and it is apparent the accuracy of the equipment was never questioned or verified. I would really would like to see a lot more skepticism on the part of researchers, technicians and medical directors as well as more openness from the equipment manufacturers.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Expiratory flow limitation exists when increasing expiratory effort fails to increase the expiratory flow rate. This can been seen when a patient exhales along the same flow-volume curve during quiet, tidal breathing as they do during a forced expiratory effort. Tidal expiratory flow limitation (EFLt) is a key concept in understanding dyspnea, hyperinflation and orthopnea in patients with COPD and in assessing the functional severity of COPD.

 

The notion that EFLt could be detected through flow-volume loops was proposed in the 1960’s but subsequent research has shown this approach to be unreliable for a variety of moderately esoteric reasons which include the differences in static lung recoil and airway resistance that occur following a deep inhalation, differences in time-dependent lung emptying and the viscoelastic forces in the lung. When tidal flow limitation as seen on flow-volume loops is compared to other techniques it is apparent that flow-volume loops overestimate the presence of EFLt by approximately one-third.

A particularly simple technique to detect EFLt, called Negative Expiratory Pressure (NEP) was developed in the mid-1990’s. In this technique a negative pressure of approximately -5 cm H2O is applied to a patient’s airway during a resting tidal exhalation. The negative pressure increases the gradient between the patient’s alveoli and their airway opening and will increase expiratory flow when there is no expiratory flow limitation. If the patient’s expiratory flow rate does not increase when negative pressure is applied then EFLt is present. A particular advantage of this technique is that it the patient breathes tidally throughout the test and does not need to perform any maximal expiratory efforts.

The apparatus for performing the NEP test is relatively simple. The patient breathes through a pneumotachograph while airway pressure is measured from a side tap between the patient mouthpiece and the pneumotach. In one version of the apparatus, on the far side of the pneumotach is a balloon-valve controlled source of negative pressure, typically a vacuum cleaner. Alternately, a venturi is supplied with solenoid valve-controlled compressed air.

 

To perform the test a patient breathes normally through the pneumotach. At the beginning of an exhalation the negative pressure is applied. At the end of exhalation the negative pressure is removed. This should be repeated several times until at least several quality tidal maneuvers have been performed and recorded. The maneuver should be performed with the patient sitting upright and while they are supine. It can also be performed during exercise on a treadmill or ergometer.

The control tidal loop and negative pressure loop are overlaid and the portion of the flow-volume loop where there was no appreciable increase in expiratory flow is considered as flow limted. This will always be less than 100% of the entire exhalation because during the beginning of exhalation flow is still increasing and it cannot be considered to be limited at that time. Additionally when the negative pressure is applied there is usually a “spike” which is considered to be the partial collapse of the extrathoracic airways and mouth.

The Functional Residual Capacity (FRC) in patients with mild to moderate COPD is smaller in the supine position than when upright. For this reason EFLt is usually present in the supine position earlier in the disease process than it is in the upright position. Many COPD patients also suffer from orthopnea for the same reason.

The severity of EFLt can be categorized using the following scale:

There is a disparity in the symptoms of chronic dyspnea in patients with similar levels of COPD as assessed by spirometry in that patients with similar FEV1’s often have quite different levels of dyspnea. This dyspnea however, has been shown to correlate with the presence or absence of EFLt at rest much better than it does with FEV1. The presence of EFLt also correlates highly with dynamic hyperinflation. Expiratory flow limitation is an issue not just in COPD, but in chronic asthma, cystic fibrosis, obesity, heart failure and the elderly as well.

NEP is a relatively simple technique that is able to provide diagnostic and staging information regarding dynamic hyperinflation, dyspnea and orthopnea that is at least as valuable as FEV1. It was first described in the mid-1990’s and yet has not been adopted by clinical PFT Labs. I can’t speak for the rest of the world but in the United States there are probably at least two reason why this is the case.

First, there is no CPT procedure code for the NEP test. Without a CPT code for NEP testing insurers will not pay for the test. The test therefore can’t be billed and there is no revenue available from it. This is not the first time that CPT coding has put limitations on Pulmonary Function testing (you need look no further than CPT 94620 which applies to both pre- and post-exercise spirometry and to 6-minute walk tests and has caused a multitude of 6MWT billing rejections) and probably won’t be the last. The CPT coding system tends to be conservative and if the NEP test has been submitted for inclusion in the CPT coding system so far it has not happened.

Second, there are no commercially available NEP testing systems. The only existing NEP testing systems have been built by researchers. Although the NEP testing system is technically simple, building, calibrating and maintaining it is probably above the skill level of most pulmonary function labs.

Finally there may also be some hesitation regarding the interpretation of results. A NEP test produces graphical results that to a large extent must be interpreted by eye. How much difference or similarity should be allowed to exist between the NEP loop and the control tidal flow-volume loop before EFLt is considered to present has not been well defined. Additionally, one technical issue in the measurement is that most investigators align the control loop and NEP loop based on the position of the patient’s end-inhalation. This may or may not be valid but the loops cannot be aligned at end-exhalation because the application of NEP always causes tidal volume to increase.

I think that NEP testing is a valuable technique and that any Pulmonary Function lab that has the resources and technical ability should consider performing it clinically. Perhaps when enough labs adopt this test then CPT codes and commercial test systems will become available.

References:

Calverley PMA, Koulouris NG. Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology. Eur Respir J 2005; 25: 186-199.

de Bisschop C, Marty ML, Tessier JF, Berberger-Gateau P, Dartigues JF, Guenard H. Expiratory flow limitation and obstruction in the elderly. Eur Resp J 2005; 26: 594-601

Duguet A, Tantucci C, Lozinguez O, Isnard R, Thomas D, Zelter M, Derenne JP, Milic-Emili J, Similowski T. Expiratory flow limitation as a determinant of orthopnea in acute left heart failure. J Amer Coll Card 2000; 35: 690-700.

Eltayara L, Becklake MR, Volta A, Milic-Emili J. Relationship between chronis dyspnea and expiratory flow limitation in patients with chronic obstructive pulmonary disease. Am J Resp Crit Care Med 1996; 154 1726-1734.

Eltayara L, Ghezzo H, Milic-Emili J. Orthopnea and tidal expiratory flow limitation in patients with stable COPD. Chest 2001; 119: 99-104.

Koulouris NG, Valta P, Laoie A, Corbeil C, Chasse M, Braidy J, Milic-Emili J. A simple methoud to detect expiratory flow limitation during spontaneous breathing. Eur Respir J 1995; 8: 306-313.

Koulouris NG, Dimopoulou I, Valta P, Finkelstein R, Cosio MG, Milic-Emili J. Detection of expiratory flow limitation during exercise in COPD patients. J Appl Physiol 1997; 82: 723-731.

Koulouris NG, Hardavella. Physiological techniques for detecting expiratory flow limitation during tidal breathing. Eur Respir Rev 2011; 20: 121, 147-155.

Pellegrino R, Brusasco V. Lung hyperinflation and flow limitation in chronic airway obstruction. Eur Respir J 1997; 10: 543-549.

Tantucci C. Expiratory flow limitation definition, mechanisms, methods, and significance. Pulmonary Medicine 2013; Article ID 749860.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

One of our testing systems has been leaking during the breath-holding period of DLCO tests. This has been an on-again, off-again problem caused by a leaking balloon valve. The odd thing about this is that the results from tests that show a patient leak are often higher than the results where they don’t.

This is not the pattern I would have expected. My initial thought would be that in the DLCO tests with a leak, the patient is spending more time at a lung volume below TLC which in turn means a lower surface area. A lower surface area should lead to a lower DLCO but this doesn’t appear to be happening.

Here are two DLCO tests from a young female patient with average height and weight. She had a normal TLC and mild airway obstruction.

 

The DLCO results from the test with the leak are 15% higher than they were from the test without the leak. There is no significant difference whatsoever in Inspired Volume, VA and breath-holding time between the two tests.

I first noticed this problem a number of years ago but I was never able to reproduce the results despite numerous trials on myself so I was never sure what to make of it. This problem only showed up rarely so I just left it as one of those mysteries you run across once in a while.

Recently however, a much larger number of patients are showing this oddball pattern of higher DLCO results when they leak than when they don’t. The only significant difference is that when I noticed this previously our test systems were all based on a volume-displacement spirometer and now we have several pneumotach-based systems capable of DLCO testing.

All of the recent (and more plentiful) examples are coming from our pneumotach-based test systems. One reason why we’re noticing this problem more frequently on these systems than we were on our volume spirometer systems may have to do with the fact that on the volume systems there were two opening in the breathing manifold that a patient could exhale through. Both had balloon valves, but if the balloon valve to the spirometer was not leaking while the other one was, then the leak would not be detected. The only time a patient leak would be detected was when the balloon valve to the spirometer was leaking. On the pneumotach-based test systems there is only one valve and any leaks around the balloon valve can only go through the pneumotach and are therefore always detectable.

Assuming that the cause of the difference in the test results is physiological there is only one thing that can elevate DLCO results and that is an increase in pulmonary capillary blood volume. Since the patients didn’t go anywhere or do anything in particular between tests an increase is unlikely to come from an increased cardiac output from exercise. A Mueller maneuver (inhaling against closed mouthpiece) causes a negative airway pressure which can pull blood into the lung and increase the pulmonary capillary lung volume. A Mueller maneuver is a difficult maneuver to perform however, and most patients are far more likely to perform some variation on a Valsalva maneuver which raises airway pressure and decreases both cardiac output and the pulmonary capillary blood volume.

One possibility however, is that the patients are performing a Valsalva maneuver at the start of the breath-holding period but that when they leak their airway pressure decreases enough to allow their cardiac output to rebound and their pulmonary capillary blood volume to increase. Even though the lung volume decreases from TLC due to the leak, this probably doesn’t decrease surface area enough to make a difference, or if it does, the increase in pulmonary capillary blood volume may be greater than any decrease in surface area. 

The fact that there is a possible physiological mechanism to explain these results does not rule out other errors in the measurement process but at the moment I have difficulty seeing what they could be. I was never able to reproduce this problem on myself however, so there may well be other factors at play here.

I think that the most important take-away from this problem is that errors in the testing process can cause increases in DLCO results as well as decreases. This means that you can never assume that a higher DLCO test result is better or more correct than other results and that DLCO test results should always be inspected carefully before they are reported.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

The issue of PFT staff licensure or certification has recently been a topic of discussion on the LinkedIn Pulmonary Function Studies group and the Diagnostics section of the AARConnect discussion board. The overwhelming majority of those posting comments have been in favor of some form of licensure or certification. CPFT (Certified Pulmonary Function Technician) and RPFT (Registered Pulmonary Function Technician) certification is discussed most often but not surprisingly on the AARConnect board most posters feel that RRT (Registered Respiratory Therapist) certification should be required as well.

I don’t think there is any argument that pulmonary function tests should be performed by qualified personnel. I will also stipulate that possession of CPFT or RPFT certification is a reasonable step in that direction. I will disagree that RRT credentials should be a requirement. The ATS-ERS recommends:

“…that completion of secondary education and at least 2 yrs of college education would be required to understand and fulfill the complete range of tasks undertaken by a pulmonary function technician.

“For pulmonary function testing, an emphasis on health-related sciences (nursing, medical assistant, respiratory therapy, etc.) is desirable. Formal classroom-style training alone does not, however, establish competency in pulmonary function testing. Technicians who conduct pulmonary function testing need to be familiar with the theory and practical aspects of all commonly applied techniques, measurements, calibrations, hygiene, quality control and other aspects of testing, as well as having a basic background knowledge in lung physiology and pathology.”

However, despite the ATS-ERS recommendations what incentive is there to become a CPFT or RPFT? At the present time (with the exception of one state) there is no legal requirement for any form of licensure or certification in order to be able to perform pulmonary function tests anywhere in the USA. Even if you don’t include those performing office spirometry, it’s been estimated that over half the staff in all pulmonary function labs lack any kind of certification.

There is also no incentive from insurers. Although Medicare requires a physician to be “at the bedside” for infant pulmonary function testing for all other pulmonary function tests they merely state that testing be “furnished by qualified personnel”. The presumption on the part of all insurers is that the staff performing pulmonary function tests are supervised and monitored by a physician who is responsible for assuring that testing is being performed correctly. I understand the logic but for most PFT Labs the reality is probably different. I’ve had close to a dozen medical directors over the years and I have liked all of them and they have all been competent and knowledgeable pulmonary physicians but at the same time all of them were far too busy to be involved in day-to-day operations.

So what can or should be done? Without incentives of some kind not much is likely to happen. Some of those posting in the forums have advocated for state licensure of Pulmonary Function labs. To them I would say be careful what you wish for. Not only do we not need another layer of bureaucracy but the only state (New Jersey) that mandates that only credentialed staff be allowed to perform pulmonary function tests requires that they be a RRT. Strange as it may seem CPFT or RPFT certification alone is not sufficient to be able to perform any test other than spirometry in New Jersey.

It is more likely that insurers will eventually act to require PFT Lab accreditation and staff credentialing. This would probably occur as part of an overall program to decrease costs by improving diagnostic testing quality. I am not aware of any specific programs in this area, but the quality of medical care continues to be subjected to more and more sophisticated analyses and PFT lab accreditation could easily become part of an overall crusade to improve the care for patients with COPD or asthma.

A critical factor that seems to be overlooked in these discussions is the distinct lack of college-level courses in pulmonary function testing. What pulmonary function testing classes I am aware of are one-semester lecture courses that are part of a respiratory therapy or exercise physiology course. They may be adequate to orient students to some of the basic issues but they do not and cannot devote the time needed for many of the esoteric yet critically important issues involved in patient testing. One reason that adequate pulmonary function classes don’t exist is probably that pulmonary function testing is a niche field. It’s difficult to make a career out of pulmonary function testing. Many small and medium sized hospital don’t even have a pulmonary function lab and there are probably over ten times as many respiratory therapists as there are pulmonary function technicians.

Since there is no incentive for credentialing those hospitals and pulmonary function labs that do require that staff be credentialed have done so through a personal decision on the part of the hospital administration, lab administrator or medical director. A good question though, is if you make this a policy in your lab, will you be able to find enough (any!) credentialed staff to meet your needs? I was a PFT Lab manager in a large teaching hospital in Boston for over 20 years yet whenever a job opening was posted I rarely had any candidates with prior experience apply and only one candidate with a CPFT (and she decided not to leave her current job despite being offered an increase in pay). The only solution I had was to hire individuals with a degree in the life sciences and then train them.

The elephant in the room in this discussion is office spirometry. My experience is that those tasked with performing office spirometry (most often medical assistants or the equivalent) are most often woefully undertrained, inexperienced and lacking any knowledge about anatomy, physiology or testing systems. They are most often trained by another medical assistant and more time is usually spent learning how to enter patient information than in how to perform the test. Many of the posters on AARConnect and LinkedIn have advocated quite strongly that all pulmonary function testing, including office spirometry, should only be performed by credentialed staff but for office spirometry this just isn’t going to happen. Even the busiest physician office is never going to perform enough spirometry to justify the expense of hiring a specialist. The best we can hope for is that the office staff get some form of professional training. For lack of anything better, the AARC offers an office spirometry certificate that requires applicants to at least pass an exam.

It takes hard work to manage a quality pulmonary function lab. Requiring the lab staff to be credentialed may simplify this but does not change the fact that there will need to be ongoing education for existing staff and that new staff will need to be trained to the lab’s and hospital’s requirements. How many resources a lab decides it has to devote to training and education will to a large extent be determined by the availability of qualified staff, however the term “qualified” is determined.

One final point is that no matter how qualified a lab’s staff, qualifications alone do not ensure test quality. Regardless of who performs a test, test quality must always monitored continually.

Update: 

Most states now require RRT, CRT, CPFT or RPFT credentials in order to work in a Pulmonary Function Lab.  For a listing of what each state requires please see State Licensure Requirements for PFT Testing.

Links:

NBRC (CPFT and RPFT credentialing)

AARC Office Spirometry Certificate program

References:

Brusasco V, Crapo R, Viegi G. Standardisation of Lung Function testing: General considerations for lung function testing. Eur Respir J 2005; 26: 153-161

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

FEV6 (the volume of air forcefully exhaled after 6 seconds) has been proposed as a replacement or surrogate for FVC in spirometry. Given that using FEV6 would simplify and speed up the spirometry test this is a seductive notion.

The use of an expired volume with a fixed expiratory time as a replacement for FVC was proposed at least 25 years ago, although at that time FEV7 was proposed as being slightly more accurate than FEV6. The first reference values for FEV6 however, were not available until the results from NHANESIII study were made available in 1999 and most studies of FEV6 post-date that.

Investigators have noted that FEV6 is less demanding than the FVC, particularly in the elderly or patients with obstructive disease. It has also been noted that the end-of-test is better defined with the FEV6 than it is with FVC and that there is a reduced possibility of syncope.

There is a fair amount of validity to the use of FEV6. FEV6 is more reproducible than FVC and a number of studies have shown that in most cases a reduced FEV1/FEV6 ratio can show airway obstruction as effectively as a reduced FEV1/FVC ratio. Use of FEV6 would simplify and reduce the amount of time that spirometry testing would take and for all these reasons a number of well-known investigators have advocated the use of FEV6. Despite this the adoption of FEV6 into routine clinical practice seems to be limited and I think there are some valid reasons for continuing to use FVC.

One reason I think that FEV6 has not made bigger inroads is partly psychological and that is because it is not the same as FVC. The vital capacity is the maximum amount of air that can possibly be exhaled whereas the FEV6 (or FEV1 or FEV3) is the amount of air that can be exhaled after a specified (and to some extent arbitrary) period of time. Although FEV6 is a useful substitute for FVC it does not reside in the same conceptual space and given the inherent conservatism in many of us this makes it difficult to think of it the same way.

The actual difference between predicted FVC and FEV6 increases with increasing age.

 

This means that the FEV1/FEV6 does not decline as rapidly as the FEV1/FVC ratio as patients age.

 

The difference between FEV6 and FVC also increases with increasing airway obstruction. When studies compared patients with reduced FEV1/FVC ratios and reduced FEV1/FEV6 ratios there was a high degree of overlap. However a certain fraction of patients have a reduced FEV1/FVC ratio but a FEV1/FEV6 ratio that is within normal limits. This means that the FEV1/FEV6 ratio is less sensitive than the FEV1/FVC ratio for detecting mild airway obstruction. It also means that a reduced FEV1/FEV6 ratio usually only exists when the FEV1 is also below the lower limits of normal.

One goal of spirometry, particularly office spirometry, is to detect airway obstruction when it is in its early stages because early intervention can reduce the long-term severity of lung disease. In this sense the FEV1/FEV6 ratio is not as sensitive as the FEV1/FVC ratio. Having said this, obtaining a quality FVC measurement can be difficult and for office spirometry the FEV1/FEV6 ratio does at least provide a clear signal.

As well as airway obstruction spirometry results are also used to assess possible restriction. For this reason a reduced FVC (with a normal FEV1/FVC ratio) is often used as an indication of a reduced TLC. At first glance it might be thought that FEV6 would be a poorer predictor of restrictive lung disease but it turns out that a reduced FVC and a reduced FEV6 are equally poor predictors of a low TLC. Regardless of the algorithm used, a reduced FVC or a reduced FEV6 (with normal or elevated FEV1/FVC and FEV1/FEV6 ratios) have only about a 50% probability of being associated with a reduced TLC. On the other hand, a normal FVC and a normal FEV6 are equally effective in ruling out restriction.

On the plus side FEV6 is more reproducible and easier to obtain than a FVC. On the minus side the FEV1/FEV6 ratio is not as sensitive an indicator of airway obstruction as the FEV1/FVC ratio. Strictly speaking, however, there is no particular reason that a place can’t be found for both the FEV6 and the FVC.

Obtaining a true, ATS-ERS standard FVC is often difficult with the elderly or patients with obstructive lung disease largely because they will require a prolonged exhalation time. Obtaining a quality FVC and FEV1/FVC ratio is likely most important during an initial visit when an accurate diagnosis is most important. Once airway obstruction has been detected however, there is no reason that a patient cannot be monitored using the FEV6 and the FEV1/FEV6 ratio during follow-up visits. For this reason my recommendation would be to include both the FEV1/FVC ratio and FEV1/FEV6 ratio on spirometry reports and for the physician reviewing the tests to switch back and forth between these ratios based on circumstances.

References:

Akpinar-Elci M, Fedan KB, Enright PL. FEV6 as a surrogate for FVC in detecting airways obstruction and restriction in the workplace. Eur Respir J 2006; 27: 374-377.

Belia V, Sorino C, Catalano F, Augugliaro G, Scichilone N, Pistelli R, Pedone C, Antonelli-Incalzi R. Validation of FEV6 in the elderly: correlates of performance and repeatability. Thorax 2008; 63: 60-66.

Ferguson GT, Enright PL, Buist AS, Higgins MA. Office spirometry for lung health assessment in adults: Consensus statement for the National Lung Health Education Program. Chest 2000; 117: 1146-1161.

Glindmeyer HW, Jones RN, Barkman HW, Weill H. Spirometry: Quantitative test criteria and test acceptability. Am Rev Respir Dis 1987; 136: 449-452.

Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. Population. Am J Respir Crit Care Med 1999; 159: 179-187.

Hankinson JL, Crapo RO, Jensen RL. Spirometric reference values for the 6-s FVC maneuver. Chest 2003; 124: 1805-1811.

Hansen JE, Sun X-G, Wasserman K. Should forced expiratory volume in six seconds replace forced vital capacity to detect airway obstruction? Eur Resp J 2006; 27: 1244-1250.

Jing JY, Huang TC, Cui W, Xu F, Shen HS. Should FEV1/FEV6 replace FEV1/FVC ratio to detect airway obstruction. Chest 2009; 135: 991-998.

Lamprecht B, Schirnhofer L, Tiefenvacher F, Kaiser B, Buist AS, Studnicka M, Enright P. Six-second spirometry for detection of airway obstruction. Am J Respir Crit Care Med 2007; 176: 460-464.

Swanney MP. Jensen RL, Crichton DA, Beckert LE, Cardino LA, Crapo RO. FEV6 is an acceptable surrogate for FVC in the spirometric diagnosis of airway obstruction and restriction. Am J Respir Crit Care Med 2000; 162: 917-919.

Swanney MP, Beckert LE, Frampton CM, Wallace LA, Jensen RL, Crapo RO. Validity of the American Thoracic Society and other spirometric algorithms using FVC and Forced Expired Volume at 6s for predicting a reduced Total Lung Capacity. Chest 2004; 126: 1861-1866.

Vandervoorde J, Verbanck S, Schueermans D, Kartounian J, Vincken W. FEV1/FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airway obstruction and restriction. Chest 2005; 127: 1560-1564.

Vandevoorde J, Verbanck S, Schuermans D, Kartounian J, Vincken W. Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6. Eur Respir J 2006; 27: 378-383. 

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.