Blog

Determining whether a subject has a ventilatory limitation to exercise used to be fairly simple since it was based solely on the maximum minute ventilation (Ve) as a percent of predicted. There has been some mild controversy about how the predicted maximum ventilation is derived (FEV1 x 35, FEV1 x 40 or measured MVV) but these don’t affect the overall approach. Several decades ago however, it was realized that subjects with COPD tended to hyperinflate when their ventilation increased and that this hyperinflation could act to limit their maximum ventilation at levels below that predicted by minute ventilation alone.

The fact that FRC could change during exercise was hypothesized by numerous investigators but the ability to measure FRC under these conditions is technically difficult and this led to somewhat contradictory results. About 25 years ago it was realized that it wasn’t necessary to measure FRC, just the change in FRC and that this could be done with an Inspiratory Capacity (IC) measurement.

The maximum ventilatory capacity for any given individual is generally limited by their maximum flow-volume loop envelope. When a person with normal lungs exercises both their tidal volume and their inspiratory and expiratory flow rates increase.

Even when maximum exercise has been attained however, flow rates tend to remain well within the maximal flow-volume loop envelope. and ventilation tends to remain around FRC.

Note: The end-exhalation volume during exercise in individuals with normal lung function often decreases below the resting FRC. Although this requires an additional expiratory effort, the elasticity of the rib cage and deformation of the abdominal wall causes this energy to be recovered during inhalation which allows tidal volume to increase with little increase in energy expenditure.

The increased compliance seen in COPD causes an increase in the time constant for lung emptying and this is due to a decrease in static lung recoil pressure and an increase in airway resistance. Expiratory flow limitation (EFL), if not already present at rest, will usually occur with relatively low increases in tidal volume and expiratory flow rates. When ventilation increases during exercise the time available for exhalation is usually not sufficient for the end-expiratory lung volume (EELV) to return to its resting level. When this occurs it is usually referred to as dynamic hyperinflation.

In patients with COPD, the increases in tidal volume that occur during exercise occur primarily within the IC. An individual with COPD may already be hyperinflated at rest which limits the available IC, and with dynamic hyperinflation IC will decrease further. In addition, as end-inspiration approaches TLC, the work of breathing increases rapidly (and this applies to everyone, not just those with COPD) due to decreasing compliance, an increasing elastic load and to the fact the respiratory muscle fibers are maximally shortened, and this acts as a further limitation to increases in tidal volume.

During exercise a subject’s FRC is referred to as the End-Expiratory Lung Volume (EELV). Changes in EELV are monitored by having a subject perform an IC maneuver at rest and then at regular intervals during testing, but it should not be performed more frequently than once every two to three minutes. This is partly because these extra deep breaths will alter gas exchange (VO2, VCO2 and RER) and partly because it is necessary to give the subject time to return to their normal EELV.

Since changes in EELV are being determined by relatively few measurements, the quality of each measurement is important. The most common issue causing suboptimal IC measurements is likely cuing the subject to start the IC improperly, and most specifically, cuing the subject after inspiration has already started. It should be remembered that it takes time for anybody to process verbal commands and for this reason, the instruction to start the IC maneuver should be completed just before the end of the subject’s exhalation. This gives them time to comprehend the request and then to be able to perform an IC maneuver without any hesitation. If the subject is cued once inspiration has already started, then the IC maneuver will likely include a significant hesitation and may be underestimated.

Most CPET systems that allow IC maneuvers to be performed will display the subject’s tidal flow-volume loops, often within the individual’s maximal flow-volume loop if that was obtained on the same testing system. The position of the tidal flow-volume loop is determined by the IC and the tidal flow-volume loops that precede and follow the IC maneuver will be recorded along with the IC maneuver. Although CPET system software will usually attempt to measure and report the EELV and IC automatically, this always needs to be verified. One factor that can make this verification difficult is a combination of volume integration drift and collecting too many tidal loops either before or after the IC maneuver.

Specifically, all CPET systems use a flow sensor of one kind or another. The flow signal needs to be integrated to derive tidal volume and there are differences in temperature, humidity and gas composition between inhaled and exhaled air. Ideally, a flow sensor should be characterized with sufficient accuracy so that the inspiratory and expiratory volumes are equal and the EELV remains constant. Practically speaking however, this is exceptionally difficult and there is usually some discrepancy between inspiratory and expiratory volumes and for this reason there is usually some drift in the position of the EELV.

IC maneuvers must be verified visually and depending on the resolution of the graphics (whether displayed on-screen or printed) and how many tidal loops were collected either before or after the IC maneuver, it can be difficult to determine where EELV was actually located.

Once accurate IC measurements have been obtained there are a number of informative calculations can be made.

ΔEELV:

An EELV measured during exercise should be compared to the baseline IC made at rest:

A positive ΔEELV indicates that the EELV has increased and depending on the amount of change, could be considered a sign of dynamic hyperinflation. Currently, there is no standard for the amount of increase that is definitive for dynamic hyperinflation, but a number of investigators have indicated that an increase in EELV at peak exercise that is ≤0.20L is probably within normal limits and one that is ≥0.25 L is likely significant. A negative ΔEELV indicates that the EELV has decreased below the resting FRC and this frequently seen in individuals with normal lung function.

Vt/IC ratio:

The Tidal Volume/Inspiratory Capacity ratio (Vt/IC) can be used as an aid in determining ventilatory reserves. In individuals with normal lung function the Vt/IC ratio at peak exercise is usually between 0.60 and 0.75. A Vt/IC ratio above 0.75 indicates the individual has a limited ability to increase their tidal volume and above 0.85 their end-inspiration is near TLC and the work of breathing is quite high.

Note: A Vt/IC ratio > 1.00 most likely means that the IC measurement was underestimated since by definition Vt cannot be greater than IC.

Due to hyperinflation, individuals with COPD may reach their maximum ventilatory capacity at a minute ventilation below what is traditionally considered as ventilatory limit (i.e. Ve > 85% of predicted) and this should be considered as a likelihood when their Vt/IC ratio is ≥0.85.

Conversely, there are individuals with more normal lung function that will have a Vt/IC ratio below 0.60 at peak exercise. This can mean a variety of things, first of which is that their primary limitation to exercise is cardiovascular, neuromuscular or musculo-skeletal rather than pulmonary, or it can just mean poor motivation.

Note: Interestingly, there are also individuals that adopt a low tidal volume, high respiratory rate response to exercise. Possible reasons for this include a reduced lung compliance, an increased respiratory drive or psychogenic causes. Regardless, it is an inefficient ventilatory response to exercise with a high Vd/Vt that will also skew Ve/VCO2 upwards. These individuals will have a low Vt/IC, high RR and a normal-ish maximum minute ventilation.

EILV/TLC:

If lung volumes are measured prior to exercise, then the End-Inspiratory Lung Volume/Total Lung Capacity ratio (EILV/TLC) can also be calculated. EILV is calculated from Vt and EELV as:

where:

Or alternately:

where:

An EILV/IC ratio >0.90 is similar, but perhaps more precise than a Vt/IC ratio >0.85 in that indicates that the end of inspiration is occurring at lung volume with an exceptionally high work of breathing. At least one study has indicated that the dyspnea during exercise was primarily related to the EILV/TLC ratio and IRV and only secondarily related to increases in EELV.

---

As with all pulmonary function measurements, a certain amount of care is necessary in performing and evaluating exercise IC measurements. Submaximal IC measurements will cause an apparent increase in EELV that is not real so it should be remembered that changes in IC are usually not abrupt. In addition, at the highest levels of exercise, when ventilatory demands are the greatest, it may be difficult for a patient to perform an IC maneuver correctly. When dynamic hyperinflation occurs, it usually occurs steadily from one IC measurement to the next. For these reasons, if there is a significant increase in EELV but this only occurs at peak exercise it should probably be ignored.

Some researchers have advocated measuring how much of the tidal expiratory loop contacts the maximal expiratory flow-volume loop envelope and using this a method for determining the degree of expiratory flow limitation. The position of the tidal flow-volume loop however, is highly dependent on the quality of the IC measurement. This, and the fact that the clinical significance that the amount of EFL gives (other than being present or absent) is unclear has meant that this type of measurement not commonly made.

Expiratory flow limitation and dynamic hyperinflation can occur in any individual with airway obstruction. Studies have shown this occurring in patients with asthma and cystic fibrosis as well as those with emphysema. My lab performs IC measurements on all CPET patients regardless of whether they have airway obstruction or not, and have found the additional information is always useful to one degree or another. At the very least it provides insight into the trajectory of increases in ventilation (Vt, RR, Ve) during exercise. More importantly, dynamic hyperinflation is both a powerful contributor to dyspnea and a significant limiting factor to an individual’s maximum exercise capacity. Decreases in IC during exercise can clearly identify those patients for whom this occurs.

Note: One final comment and that is I’ve had the chance to work with CPET systems from only a small number of manufacturers. For this reason I am far from sure how universal a findings this is but none of them have allowed the ability to modify any of the automatically measured IC’s and so the ΔEELV‘s and Vt/IC ratios that appear in the CPET system reports are often wrong. It’s not clear how this should be corrected and I suppose the answer, if there is one, will differ from one system to another. My approach to correcting this (and many of the other problems with CPET reports) is time consuming and highly idiosyncratic, and I will save it for a general discussion of tests with reporting problems.

References:

ATS/ACCP Statement on cardiopulmonary exercise testing. Amer J Respir Crit Care Med 2003; 167(1): 211-277.

Gagnon P, Guenette JA, Langer D, Laviolette L, Mainguy V, Maltais F, Ribeiro F, Saey D. Pathogenesis of hyperinflation in chronic obstructive pulmonary disease. Int J COPD 2014; 9: 187-201.

Guenette JA, Webb KA, O’Donnell DE. Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD? Eur Respir J 2012; 40: 322-329

Henke KG, Sharratt M, Pegelow D, Dempsey JA. Regulation of end-expiratory lung volume during exercise. J Appl Physiol 1988; 64(1): 135-146.

Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: The exercise tidal flow-volume loops. Chest 1999; 116: 488-503.

Kosmas EN, Milic-Emili J, Polychronaki A, Dimitroulis I, Retsou S, Gaga M, Koutsoukou A, Rousshos C, Koulouris NG. Exercise-induced flow limitation, dynamic hyperinflation and exercsie capacity in patients with bronchial asthma. Eur Respir J 2004; 24: 378-384.

O’Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 158: 1557-1565.

O’Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. Eur Respir Rev 2006; 15: 61-67.

O’Donnell DE. Hyperinflation, dyspnea and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006; 3: 180-184.

Pellegrino R, Brusasco V, Rodarte JR, Babb TG. Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol 1993; 74(5): 2552-2558.

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

We have a number of patients who have spirometry and DLCO testing performed at regular intervals. I’ve noticed that every so often DLCO results change significantly without a change in spirometry (or lung volumes) or there’s a modest change in spirometry and a marked change in DLCO. I’ve been concerned that this may be a symptom of problems with our DLCO (CO/CH4) gas analyzers and at least once recently this kind of discrepancy did lead to having an analyzer being serviced. Realistically though, the gas analyzers are routinely passing their calibrations and when I look at the trends in calibration there hasn’t been any systematic drift. This doesn’t rule out intermittent problems however, so in order to find out whether these changes in DLCO are “real” or an artifact of our testing systems I decided to see if taking a closer look at the results would help resolve this.

First, what constitutes a significant change in DLCO?

My lab’s current working definition is an increase or decrease in DLCO that is ≥2.0 ml/min/mmHg or ≥10%, whichever is greater. This is slightly different from the ATS/ERS DLCO intra-session repeatability requirements (≥3.0 ml/min/mmHg or ≥10%) and may mean that we’re setting the bar too low but there’s a difference between intra-session and inter-session variability. Specifically, we average the two closest results (assuming there are at least two tests of good quality) from one testing session to another and it is the inter-session average we are comparing, not individual tests and for this reason we feel that a smaller change can be relevant.

Note: The ATS/ERS statement on interpretation does discuss inter-session DLCO variability but there it is expressed as >7% within the same day and >10% year to year without setting an upper limit. The year to year value is based solely on a study from 1989 on eight individuals using a manually operated testing system (Collins Modular Lung Analyzer) that used a semi-automated alveolar sampling bag and for this reason it’s hard to be sure it is still relevant.

Second, which test parameters have the greatest effect on calculated DLCO?

As a reminder, the DLCO formula is:

Where:

VA = alveolar volume (in ml)

BHT = breath-holding time (in seconds)

Pb = barometric pressure (in mmHg)

FI_Trace = inspired concentration of the tracer gas (helium, methane, neon)

FA_Trace = exhaled (alveolar) concentration of the tracer gas

FICO = inspired concentration of Carbon Monoxide

FACO = exhaled (alveolar) concentration of Carbon Monoxide

And:

Where:

Deadspace volume = machine deadspace + anatomic deadspace

In these two formulas FI_Trace, FICO, PH2O and Deadspace volume are essentially constants and do not change from session to session. Pb may change slightly but its effect is insignificant and can be ignored. Of the remaining parameters FACO will of course have a direct bearing on DLCO, but any changes in BHT tends to cancel themselves out and this is because a longer BHT usually leads to a lower FACO and a shorter BHT leads to a higher FACO. DLCO is therefore going to depend most strongly on FACO, VA, Inspired Volume (VI) and FA_Trace and less so on BHT. VA, VI and BHT are primarily patient performance issues, while FACO and FA_Trace are gas analyzer issues.

Note: Hemoglobin also has a significant effect, but I selected only DLCO tests that had been corrected for hemoglobin for this analysis.

So what do these changes look like?

	Session 1:	%Predicted:	Session 2:	%Predicted:
FVC:	2.69	102%	2.60	99%
FEV1:	2.06	104%	1.97	100%
FEV1/FVC:	76%	102%	76%	101%
DLCO:	15.18	91%	13.01	78%
VA:	4.01	88%	3.88	85%
VI:	2.71		2.63
FACH4:	59.32		60.74
FACO:	33.28		36.87
BHT:	10.63		10.43

Both sessions have DLCO tests that meet the ATS/ERS standards for quality and repeatability. The difference in FVC, FEV1, VA, VI, BHT and FA_CH4 are minimal. The primary difference is in FACO with about a 10% decrease in CO uptake in the second session when compared to the first. Since there doesn’t seem to be any performance or gas analyzer issues this change in DLCO is likely real.

	Session 1:	%Predicted:	Session 2:	%Predicted:
FVC:	2.93	63%	3.10	67%
FEV1:	2.34	67%	2.35	68%
FEV1/FVC:	80%	107%	76%	101%
DLCO:	15.16	58%	18.30	70%
VA:	4.19	60%	4.18	60%
VI:	3.27		2.97
FACH4:	69.84		62.21
FACO:	40.15		31.81
BHT:	10.63		10.66

Although there are minimal changes in spirometry values there was a test performance difference with about a 10% decrease in VI in the second session. Interestingly, the VA is the same between both sessions which implies a similar degree of expansion and gas mixing within the lung. What’s suspicious about these tests is that both the FACH4 and the FACO are lower than in the first session and that in an absolute sense the decrease in FACH4 and FACO are similar (-7.63 vs -8.34).

A similar change in absolute values is something you would expect if there had been a shift in the analyzer’s zero or span. Our tests systems perform a zero and span check before every test and when I checked I found them both to be within normal limits for both sessions. Despite this, this one remains suspicious to me.

	Session 1:	%Predicted:	Session 2:	%Predicted:
FVC:	3.11	68%	3.03	67%
FEV1:	2.63	70%	2.57	69%
FEV1/FVC:	84%	101%	85%	102%
DLCO:	17.19	73%	15.01	63%
VA:	4.01	65%	3.63	59%
VI:	3.15		2.96
FACH4:	67.35		67.91
FACO:	35.34		36.76
BHT:	10.47		10.33

Again minimal changes in spirometry and although there were minimal differences in FA_Trace and FACO the VI was slightly (-6%) less in the second session. There was a more significant decrease in VA however (-9%) and in fact this alone was likely the major cause of the difference in DLCO between the two sessions.

Assuming all other values remain the same DLCO scales linearly with VA.

There were only small differences in most parameters between the two sessions but the difference in DLCO was 2.18 ml/min/mmHg (-13%) and this seems to be due to a decrease in VA of -9% and a decrease in FACO of -4%.

So in this particular case even though the DLCO tests in both test sessions met all ATS/ERS criteria for acceptability, there were performance issues that are likely responsible for most of the difference in DLCO and only small changes in CO uptake that are responsible for the rest.

	Session 1:	%Predicted:	Session 2:	%Predicted:
FVC:	2.39	56%	2.90	69%
FEV1:	1.81	56%	2.07	65%
FEV1/FVC:	76%	100%	71%	95%
DLCO:	22.26	86%	16.54	64%
VA:	4.12	64%	4.45	69%
VI:	2.56		2.85
FACH4:	51.67		56.60
FACO:	21.77		32.06
BHT:	10.88		10.62

There were significant improvements in spirometry from the first to the second session yet despite this the DLCO decreased by 27%. It could be argued that even though the FEV1 increased the decrease in the FEV1/FVC ratio indicates that airway obstruction was actually slightly more severe but the FEV1/VI ratio from the first session was also 71% so there really was no change. Both sets of DLCO tests met the ATS/ERS criteria for acceptability and reproducibility.

The biggest difference between the two sessions is the FACO and this implies that CO uptake was markedly better in the first session than the second. I could argue that the FACO from that session is too low but given the minimal differences in VA and the fact that there was no systematic difference in FACH4 and FACO I’m going to reluctantly say this is more likely due to changes in the patient’s clinical status.

	Session 1:	%Predicted:	Session 2:	%Predicted:
FVC:	4.00	93%	4.22	98%
FEV1:	2.47	78%	1.95	61%
FEV1/FVC:	62%	84%	46%	63%
DLCO:	11.84	47%	5.88	24%
VA:	5.44	81%	5.15	77%
VI:	2.44		4.09
FACH4:	39.45		72.83
FACO:	31.14		62.15
BHT:	8.94		10.71

The FEV1 decreased significantly in the second session but the DLCO decreased much more. This however may be comparing apples to oranges. The first session did not meet the ATS/ERS standards for quality or reproducibility (only one vaguely acceptable test was performed) and the VI is quite low compared to the FVC.

What this likely points out is that the ventilation and perfusion of the lung is not homogenous. Just as importantly, an inhaled breath is not homogenously distributed. Assuming that the patient inhaled to TLC in both instances, this may mean that the lower volume of the first session was preferentially distributed to the more highly perfused portions of the lung while during the second session the inhaled volume was distributed to both high and low perfused areas of the lung.

This doesn’t rule out clinical changes but there were substantial performance issues between both sessions and the difference in DLCO is more likely attributable to this. It also means that a better quality test does not mean a higher DLCO.

---

These comparisons are limited by the fact that the tests were performed at least a couple months apart. There is also no easy way to track which test system each set of tests were performed on (it can be done but it requires a complicated SQL query that must be run for each individual test) and my lab has six test systems that can perform DLCOs. In a sense though, that’s the point. Unless a PFT Lab has only one DLCO test system then a patient’s testing will usually be performed on whatever system is available and convenient. It’s also the point since the daily calibrations (and other quality control) are supposed to make sure that testing is accurate and repeatable regardless of which test system is being used.

Interestingly, while searching for changes in DLCO over the last couple of weeks what I found in most instances was that these changes were accompanied by changes in spirometry and/or lung volumes, and the direction of the changes were similar. When there were changes in DLCO without changes in spirometry, the majority were similar to the first example in that the primary change seemed to be in CO uptake alone and not in test performance. The next most common problem were changes in test performance and as can be seen from above sometimes even a relatively small change in performance can lead to a significant change in DLCO. There were actually remarkably few tests that were suspicious for gas analyzer problems and this reassures me that our equipment is in better shape than I expected.

DLCO results often rise and fall for reasons that are not completely clear. Many of the possible physiological causes for this such as cardiac output, capillary blood volume, the distribution of the inhaled volume and ventilation-perfusion mismatching cannot be measured directly. I was cautiously pleased to see that more often than not DLCO results did not change when there was no significant change in spirometry and/or lung volumes and this is despite the fact that the tests were likely performed on different systems. I think that one key to this is that DLCO results are usually averaged but the other is the constant calibration that the testing systems undergo and the highly standardized way in which the DLCO is performed.

References:

Brusasco V, Crapo R, Viegi G. ATS/ERS Task Force: Standarisation of lung function testing. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26: 720-735.

Brusasco V, Crapo R, Viegi G. ATS/ERS Task Force: Standarisation of lung function testing. Interpretive strategies for lung function tests. Eur Respir J 2005; 26: 948-968.

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

For a variety of reasons my wife recently had a full panel of PFTs (spiro+BD, lung volumes, DLCO) at a different hospital than the one I work at. I went with her and was pleased to see the technician perform the tests pleasantly, competently and thoroughly. I was able to glance at the results as the testing proceeded so I had a fairly good idea what the overall picture looked like by the time she was done.

The difficulty came later when my wife asked me to print out her results so we could go over them together. Many hospitals and medical centers have websites that let patients email their doctor, review their appointments and access their medical test results. They go by a variety of names such as MyChart, MyHealth, Patient Gateway, PatientSite, PatientConnect etc., etc. My hospital first implemented something like this over a dozen years ago so I had thought that by now they were fairly universal but conversations with a couple of friends from around the country have let me know that this isn’t really the case.

Regardless of this, the hospital where my wife had her PFTs does have a website for patients and her PFT results showed up about a week later. When I went to look at them however, I was completely taken aback. Not because the results were wrong but because they were presented in a way that made them incredibly difficult to read and understand.

Here’s the report (and yes, this is exactly what it looked like on the patient website):

Component	Standard Range	Your Value
FVC Pre	2.62-3.28 L	2.11
FEV.5 Pre		1.25
FEV1 Pre	1.97-2.53 L	1.51
FEV3 Pre		1.9
FEF200-1200 Pre		2.54
PEF Pre	4.88-6.52 L/s	5.44
PEFT Pre		0.08
FIVC Pre		1.8
PIF Pre		4.1
Vol Extrap Pre		0.03
FEV6 Pre		2.08
StdFEF25-75 Pre		1.06
FEV2 Pre		1.77
Vtg Pre		1.75
Vtg f Pre		43.3
VC Pre	2.62-3.28 L	2.11
TLC Pre	4.21-5.2 L	3.48
RV Pre	1.65-2.23 L	1.37
FRC PL Pre	2.22-3.04 L	1.76
ERV Pre	0.81-1.03 L	0.37
IC Pre	1.62-2.06 L	1.72
VE Pre		13.63
Vt Pre		0.65
LCI Pre		21.05
DLCO/VA Pre	19.27-26.67 ml/mmHg/min	14.52
VA Pre		4.37
CO T.C. Pre	4.43-5.27 L	2.87
IVC Pre		13.77
FI CH4 Pre		1.89
FE CH4 Pre		0.3
FI CO Pre		0.17
FE CO Pre		0.3
BHT Pre		0.08
CH4 Delta Pre		10.8
FEV1/FVC Pre		72
RV/TLC Pre		39
Kroghs K Pre	5.02-6.41 ml/mmHg/min/L	5.05
FVC Post	2.62-3.28 L	2.26
FEV.5 Post		1.38
FEV1 Post	1.97-2.53 L	1.64
FEV3 Post		2
FEF200-1200 Post		3.53
PEF Post	4.88-6.52 L/s	6.01
PEFT Post		0.1
FIVC Post		2.03
FIV1 Post		1.76
PIF Post		3.88
Vol Extrap Post		0.04
FEV6 Post		2.21
StdFEF25-75 Post		1.06
FEV2 Post		1.84
VC Post	2.62-3.28 L	2.26
ERV Post	0.81-1.03 L	0.25
IC Post	1.62-2.06 L	2.04
VE Post		12.75
Vt Post		0.72
LCI Post		17.63
FEV1/FVC Post		73
TLC Pred	4.21-5.2 L	4.7
FEV1 Pred	1.97-2.53 L	2.25
FVC Pred	2.62-3.28 L	2.95
CO T.C. Pred	4.43-5.27 L	4.85
FRC PL Pred	2.22-3.04 L	2.63
IC Pred	1.62-2.06 L	1.84
RV/TLC Pred	36.7-46.29 %	41.49
Kroghs K Pred	5.02-6.41 ml/mmHg/min/L	5.71
ERV Pred	0.81-1.03 L	0.92
RV Pred	1.65-2.23 L	1.94
DLCO/VA Pred	19.27-26.67 ml/mmHg/min	22.97
VC (SBO2) Pred	2.22-3.04 L	2.63
VC Pred	2.62-3.28 L	2.95
PEF Pred	4.88-6.52 L/s	5.7
FEV1/FVC Pred	71.83-81.62 %	76.73
FRC N2 Pred	2.22-3.04 L	2.63
FVC %Pre Pred		71.46
FEV1 %Pre Pred		67.25
PEF %Pre Pred		95.42
VC %Pre Pred		71.46
TLC %Pre Pred		73.94
RV %Pre Pred		70.63
FRC PL %Pre Pred		67.05
ERV %Pre Pred		40.14
IC %Pre Pred		93.34
DLCO/VA %Pre Pred		63.23
CO T.C. %Pre Pred		59.27
Kroghs K %Pre Pred		88.44
FVC %Post Pred		76.61
FEV1 %Post Pred		72.8
PEF %Post Pred		105.42
VC %Post Pred		76.61
ERV %Post Pred		27.31
IC %Post Pred		111.13
FVC %Chng		7
FEV.5 %Chng		10
FEV1 %Chng		9
FEV3 %Chng		5
FEF200-1200 %Chng		39
PEF %Chng		10
PEFT %Chng		25
FIVC %Chng		13
PIF %Chng		-5
Vol Extrap %Chng		33
FEV6 %Chng		6
StdFEF25-75 %Chng		0
FEV2 %Chng		4
VC %Chng		7
ERV %Chng		-32
IC %Chng		19
VE %Chng		-6
Vt %Chng		11
LCI %Chng		-16

If you were able to follow this report then I commend you. But now put yourself in the shoes of a patient that is also trying to make some sense of their test results. Personally, I’d say the odds of any patient being able to understand this report are pretty slim. There’s so much wrong with the way this report is structured it’s difficult to know where to start.

I think the first thing that makes it hard to read is that there is no separation of the results between different tests so unless you’re knowledgeable you wouldn’t know where the results for the spirometry, lung volume and DLCO tests started or ended. For that matter, it’s hard to say that they’re correctly grouped in the first place since the FEV1/FVC ratio and RV/TLC ratio are placed just after the DLCO results.

The second is that the values for the pre-bronchodilator, post-bronchodilator, predicted, percent predicted and percent change are separated on the report and are not at all easy to compare. On the website they all tend to fall on different pages and no matter how you scroll you can’t see more than part of each of these categories.

Third, there are an awful lot of extraneous values. When was the last time you saw FEF200-1200, FEV0.5, FEV2, PIF, FI CH4 and FE CO (among many others) on a report?

Fourth, and in some ways worst of all, there are results that are mis-labeled or at least labeled in non-standard ways. DLCO/VA is (probably) DLCO. BHT should be Breath Holding Time but the value reported for it was 0.08 and it should really be something like 10-12. IVC should be the DLCO Inspired Volume (at least it should be since it’s embedded in the DLCO results) but the value reported for it was 13.77 and the FVC and VC were 2.11 so what is it really?. FI CH4 is 1.89 but the FE CH4 is 3.00 and this is the opposite of what they should be. Ditto FI CO and FE CO. The results for Krogh’s K were 5.05 but the DLCO is 14.52 and VA is 4.37 so it should really be 3.32 (and why was the VA [4.37] larger than the TLC [3.48] so is it really correct?). I can guess but I’m not totally sure what stdFEF-25-75 is (probably not isoFEF25-75) and I have absolutely no idea what PEFT, VE, CO T.C., LCI or VC(SBO2) are.

Note: I’m also not certain where the values in the standard range come from. I know the lab uses the NHANESIII reference equations for spirometry and the standard range in this report is not the NHANESIII LLN and ULN.

Finally, and most importantly of all, where’s the interpretation?

So, the report that’s made available to patients is extraordinarily hard to read with mis-labeled results, no interpretation and is therefore pretty much useless. How in the world did it end up this way?

I actually had a conversation with the medical director of the lab about this and was told that they had tried very hard to get this fixed but it was more or less the default setting in their hospital’s information system (a commercial system found in many hospitals) and that the hospital’s IT department did not consider fixing this to be any kind of a priority whatsoever.

The problem therefore, starts with choices made by the vendor of the hospital information system. There is likely some ability to change and customize the settings but rightly or wrongly the keys to this are held by the IT department and the reality is that within any hospital, just like the capital budget and room space, IT is a limited resource. Pulmonary function labs are a niche specialty and even in the largest hospitals they are small and have limited clout. IT resources are deployed based on perceived need and pulmonary function labs have to compete for them against significantly larger departments that probably contribute exponentially more to the hospital’s bottom line.

If I was asked what I’d do to try to fix this I’d say that it’s important to be as specific as possible with any request to IT so my first step would be to request the documentation relating to customizing the patient website reports. After determining what is and what is not possible (for example I’d prefer to have the results in a more-or-less standard table but this function may not be supported) I’d create a very specific list of changes.

Next, in order to get the request back on IT’s radar I’d label it first as a patient safety issue with possible legal implications (because of the mis-labeled results). I’d also label it as a patient healthcare management issue (improving patient outcomes and reducing re-admissions). Finally, I’d also label it as a patient marketing problem and then re-submit the issue to IT and the hospital administration.

Even so, no matter what arguments you can muster it may well be possible that the hospital’s IT department is already running around putting out fires as fast as it can and truly does not have the resources to fix this problem. That doesn’t mean you can’t get your ducks in a row and be persistent. It also doesn’t mean you can’t think about alternate (and hopefully temporary) solutions such as printing a preliminary copy of the patient’s report and handing it to them as a visit summary before they leave the lab.

Before I ran into this problem I didn’t know just how spoiled I was. For at least the last 10 years my lab’s patients have been able to read and download PDF copies of the same reports we send the physicians and these include the results, graphs, trends and interpretation. I always thought this was a fairly straightforward solution and never thought it was that much of a problem to implement. I’ve had my battles with IT (starting when we got our first network and hospital computer system interface in the early 1990’s) but eventually the lab always got some kind of functional solution. In retrospect, it’s apparent that I had it easy.

For decades after I started in this field nobody but the pulmonary physicians cared what was on our reports and what they looked like. Now we’re completely dependent on the hospital’s IT department to manage both our data and our reports. They in turn are often looking to other departments like Medical Records, Budgeting and Compliance for guidance and we have less say than ever in what our reports look like, how they are managed and what kind of priority our problems have.

But also for decades the best a patient could do to manage their results was to get permission to photocopy their reports and then hand-collate them (and we’d also look somewhat askance at those patients as being self-absorbed and possible hypochondriacs). Now it’s widely accepted that patients need to be partners in their own health care and for this reason they also need to have access to all their clinical information. Many (but not all) hospitals and medical centers now have websites that make this clinical information readily available to their patients and like it or not, it’s another area that needs to work for our patients and for that reason is now another one of our responsibilities.

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

Airway hyper-responsiveness is a primary feature of asthma. There are a number of bronchial challenge tests designed to evoke and measure this factor, the most common of which require the inhalation of one or another bronchoconstrictive agent such as methacholine, histamine, mannitol or hypertonic saline.

An elevated ventilation can cause many asthmatics to bronchoconstrict and this is often the cause of Exercise-Induced Bronchospasm (EIB). There are two competing theories as to why this happens. A number of researchers have suggested that the mechanism is a drying of the airway mucosa which changes the osmolarity of the respiratory tract fluid which in turn causes some cells to releases mediators that cause bronchoconstriction. Other researchers assert that it is the cooling of the airways during hyperventilation and an increased blood flow and edema during subsequent re-warming that causes the bronchoconstriction. There is evidence to support both interpretations and it is likely that both mechanisms coexist, with one or the other being more predominant in any given individual.

Although the inhalation challenge tests are reasonably sensitive not all patients with EIB have a positive reaction. When a patient’s primary complaint is exercise-related or when they have had a negative inhalation challenge test and are still symptomatic, a ventilatory challenge test should be considered. There are several ventilatory challenge tests that are specifically oriented towards evoking and characterizing EIB. These are the Cold Air challenge, Eucapnic Voluntary Hyperventilation and Exercise Challenge. There are a number of similarities between these tests.

Cold Air Challenge

A Cold Air Challenge (CACh) test consists of having a patient hyperventilate while breathing air that has been cooled to a temperature of between -10°C and -20°C. It is usually performed using a mixture of 5% CO2, 21% O2, 74% N2 in order to prevent dizziness from hypocapnia.

Note: some researchers have added carbon dioxide to compressed air rather than using a mixture. Although this lowers the cost of the compressed gases used during the challenge this also requires constant titration of the carbon dioxide flow rate in order to maintain a subject’s PETCO2 at a normal level, which in turn requires an end-tidal CO2 monitor. At least one study showed that 5% CO2 in air maintained a reasonably normal PETCO2 in most subjects across a very wide range of minute ventilations and because this simplifies the testing process a 5% CO2 gas mixture is more commonly used.

The period of hyperventilation is usually 3 to 4 minutes. A number of researchers have used hyperventilation periods of up to 6 minutes but several studies have shown that 3 minutes is usually sufficient to induce bronchoconstriction.

Cold air challenges can be performed with a single level of ventilation or with multiple levels. The advantage of performing a cold air challenge at multiple levels is that it makes it possible to determine what level of ventilation causes bronchoconstriction. When this is done minute targets ventilation are usually 10%, 20%, 40% and 80% of an individual’s observed MVV (or 4, 8, 16 and 32 times the observed FEV1). The disadvantage is that this process can be extraordinarily time consuming. Peak bronchoconstriction usually occurs by 15 minutes post-exposure but more than one investigator has indicated there is a refractory period of up to 60 minutes following exposure. For this reason most cold air challenges are performed with a single level and with a minute ventilation target that ranges from 15 to 30 times the FEV1 or 40% to 80% of measured MVV.

Changes in FEV1, SGaw. SRaw and oscillometry have been used to assess bronchoconstriction following exposure to cold air. FEV1 should be measured at 5 minute intervals up until at least 15 minutes post-exposure. SGaw can be measured as frequently as every 2 minutes post-exposure, but measurements should also continue up to 15 minutes post-exposure. There is no real consensus as to what constitutes a positive response and different researchers have indicated that a positive response for FEV1 is a decrease that ranges from a 9% to 20% and for SGaw it is a decrease that ranges from 30% to 50%. Even though studies performed with presumably normal individuals have shown decreases in FEV1 of up to 10% and SGaw up to 30% the most common guidelines indicate that a 10% decrease in FEV1 and 30% decrease in SGaw should be considered significant. Interestingly, one study indicated that the sensitivity to cold air declined with age but unfortunately this finding has not been confirmed.

Changes in oscillometry values are more difficult to characterize, partly because of differences in equipment (IOS vs FOT) but also in nomenclature. One study using FOT noted increases in resistance at 8 hz and 28 hz, decreases in reactance at 8 hz and an increase in resonant frequency from 12 to 25 hz. Another study using IOS found significant change in R5, X5, X35 and a doubling of the resonant frequency from 12 to 24 hz.

One of the primary technical problems with cold air challenges is providing cold air. Many of the research studies involving cold air used custom-built systems with a variety of refrigeration units and heat exchangers.

At the present time the only cold-air system for medical use appears to be the TurboAire Challenger from Vacumed.

Note: This device is a Ranque-Hilsch vortex tube and is a fascinating application of atmospheric physics.

[vortex tube found on youtube, posted by ITW Vortec]

Compressed gas is injected tangentially into a tube. This cause the rapid rotation of air within the tube (up to 1,000,000 RPM!). This in turn causes warm air and cold air to separate and in fact, air loses temperature through a decrease in angular momentum as it acts to increase the radial velocity of the outer layer. Warm air is in the outer layer and exits one end of the tube. Cold air is in the interior of the tube and exits the other end. In one sense this device is inefficient since the majority of the compressed gas is warmed and therefore unusable for testing. On the other hand, there are no moving parts and no bulky refrigeration units or heat exchangers. The TurboAire requires compressed air at 80-110 PSI and flow rates (not published) above what can be provided by hospital wall outlet. For these reasons the source gas will need to be provided by a regulator and gas cylinder.

An additional technical problem is monitoring a patient’s minute ventilation during the cold air challenge. Depending on the actual layout of the cold air system this has been done by controlling the flow of gas to a reservoir (Douglas bag), collecting exhaled air in a reservoir and evacuating it at a controlled rate, with an in-line gas meter, or with a flow sensor. Finally, inspiratory temperature should be measured in order to assure the proper gas temperature is being provided.

Eucapnic Voluntary Hyperventilation

In a real sense, the Eucapnic Voluntary Hyperventilation (EVH) test is a cold air challenge without the cold air, and in fact the EVH was developed after the CACh. Like the CACh subjects breath a mixture of 5% CO2, 21% O2, 74% N2 to prevent hypocapnia. In general there are two different protocols; stepped and single-stage. An example of a stepped EVH would be 3 to 6 minutes of ventilation at:

1) 30% of the MVV

2) 60% of the MVV

3) 90% of the MVV

where MVV is calculated from FEV1 x 35, with spirometry at regular intervals out to 10 minutes following each stage. An example of a single-stage protocol would be 85% of the MVV (FEV1 x 35) for 6 minutes, with spirometry at regular intervals out to 15 minutes.

Although a multiple-step protocol can give some notion as to what constitutes a triggering level of ventilation, at least one study showed that the level of bronchoconstriction, when it occurred, was less than that for a single-step protocol.

One study showed that at decrease in FEV1 greater than 11.3% was outside the 95% confidence limits but other researchers have indicated that a decrease of 10% within 5 to 10 minutes post-hyperventilation should be considered as positive.

The advantage that EVH has over CACh is a simplified testing apparatus without the need to provide cold air. The disadvantage is that it tends to require a higher minute ventilation and for a longer period of time and this may place a limit on which patients can perform it. There is also some evidence that EVH does not evoke as great a bronchoconstrictive response as cold air. One study that compared the two techniques showed a mean decrease in FEV1 of 11.7% with EVH compared to a mean decrease in FEV1 of 20.4% with CACh in the same subjects.

Exercise Challenge

The ATS published standards for exercise challenge testing as part of the standards for methacholine challenge testing. The primary recommendations are the use of a treadmill or bicycle ergometer but field testing, i.e. where the subject exercises outdoors performing the activities that usually lead to their symptoms can also be performed. Since hypocapnia does not occur with exercise the testing is performed with room air. The ATS standards recommended a humidity content less than 10 mg/L but a number of researchers indicate that it should be supplied from a cylinder in order to assure a humidity level of less than 3 mg/L. A number of researchers have combined a CACh with an exercise challenge by providing cold, dry air during exercise.

For safety heart rhythm should be monitored with a 12-lead or 3-lead ECG. The level of exercise is determined by the workload need to either attain a heart rate of 80%-90% of the predicted maximum or to attain a ventilation of 40%-60% of the MVV (FEV1 x 35). In general the exercise workload should progress until the target heart rate or ventilation is achieved and then is maintained at that level for a minimum of 4 minutes. Spirometry is performed at 5, 10, 15, 20 and 30 minutes post-exercise and a positive response is a 10% decrease in FEV1.

Interestingly, although the point is to determine the presence of exercise-induced bronchoconstriction, numerous researchers have shown that an exercise challenge test, which includes field testing, is significantly less sensitive (and less specific) than cold air or eucapnic voluntary hyperventilation challenge tests.

---

For all of the ventilatory challenge tests most of the same contraindications as for a methacholine or histamine challenge should be applied. Baseline FEV1 should not be less than 65%-75% of predicted and unless their effectiveness is specifically being tested inhaled bronchodilators and steroids should be withheld prior to a challenge. Although severe bronchoconstriction is relatively uncommon it is always a possibility and for this reason the appropriate medications and the ability to summon more advanced aid should always be present.

Given that most of the early cold air systems were custom-built there is likely the perception that performing cold air challenges is difficult and beyond the ability of the average pulmonary function lab. This is not really true since the cost of a TurboAire Challenger is in the same ballpark as many spirometry systems. It also has no moving parts, making it simple to use and maintain.

Note: I have not used the TurboAire Challenger and have no connections with Vacumed, financial or otherwise. I have worked with a cold air challenge system in the past (and repaired it numerous times) but it was custom built using a refrigeration unit that circulated -40°C isopropyl alcohol through a copper heat exchanger.

EVH systems are even simpler however, and can often be built with equipment that a PFT lab may already have on hand so why these are also not more commonly found in pulmonary function labs is unclear.

The Methacholine challenge is probably the most commonly performed test to assess bronchial hyperreactivity. Cold air challenges and Eucapnic Voluntary Hyperventilation are much less commonly performed, and are most often seen in conjunction with sports medicine. Part of the reason for this is that estimates of the prevalence of EIB among athletes range from 11% to as high as 50% depending on the sport, and not surprisingly the higher numbers come from those athletes that are primarily exposed to cold air such as figure skaters and cross-country skiers.

CACh and EVH have been shown to be more specific to EIB than methacholine challenge tests. More than one study has noted that some subjects within their study group responded to methacholine but not cold air and vice versa. Similarly, even for individuals that do respond to both methacholine and cold air there is often a lack of correspondence between the methacholine PC20 and the decrease in FEV1 following cold air. For all these reasons it has been speculated that EIB is actually different from asthma and it would also seem that EIB is best assessed by CACh or EVH.

Addendum:

CPT code 95070: Inhalation bronchial challenge testing (not including necessary pulmonary function tests); with histamine, methacholine, or similar compounds.

CPT code 94070 Bronchospasm provocation evaluation, multiple spirometric determinations as in 94010, with administered agents (eg, antigen[s], cold air, methacholine)

CPT code 94620 Exercise test, simple

References:

American Thoracic Society. Guidelines for Methacholine and Exercise testing – 1999. Amer J Respir Crit Care Med 2000; 161(1): 309-329.

Anderson SD, Argyros GJ, Magnussen H, Holzer K. Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J Sports Med 2001; 35: 344-347.

Anderson SD, Brannan JD. Methods for “indirect” challenge tests including exercise, eucapnic voluntary hyperventilation, and hypertonic aerosols. Clin Rev Allergy Immunol 2003; 24: 27-54.

Argyros GJ, Roach JM, Hurwitz KM, Eliasson AH, Phillips YY. The refractory period after eucapnic voluntary hyperventilation challenge and its effect on challenge technique. Chest 1995; 108(2): 419-424.

Aquilana AT. Comparison of airway reactivity induced by histamine, methacholine, and isocapnic hyperventilation in normal and asthmatic subjects. Thorax 1983; 38: 766-770.

Bauer I, Weisner MD. Cold air bronchial provocation. Technical issues and protocol. Copyright 1998, Equilibrated Bio Systems Inc.

Ben-Dov I, Gur I, Bar-Yishay E, Godfrey S. Refractory period following induced asthma: contributions of exercise and isocapnic hyperventilation. Thorax 1983; 38(10): 849-853.

Carlson K-H, Engh G, Mork M, Schroder E. Cold air inhalation and exercise-induced bronchoconstriction in relationship to methacholine bronchial responsiveness: different patterns I asthmatic children and children with other chronic lung diseases. Respiratory Medicine 1998; 92: 308-315.

Eliasson AH, Phillips YY, Rajagopal KR. Sensitivity and specificity of bronchial provocation testing. An evaluation of four techniques in exercise-induced bronchospasm. Chest 1992; 102(2): 347-355.

Evans TM, Rundell KW, Beck KC, Leving AM, Baumanns JM. Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise. Chest 2005; 128: 2412-2419.

Filuk RB, Serrette C, Anthonisen NR. Comparison of responses to methacholine and cold air in patients suspected of having asthma. Chest 1989; 95: 948-952.

Heaton RW, Henderson AF, Gray BJ, Costello JF. The bronchial response to cold air challenge: evidence for different mechanisms in normal and asthmatic subjects. Thorax 1983; 38: 506-511.

Heaton RW, Henderson AF, Costello JF. Cold air as a bronchial provocation technique. Reproducibility and comparison with histamine and methacholine inhalation. Chest 1984; 86(6): 811-814.

Koskela HO, Rasanen SH, Tukiainen HO. The diagnostic value of cold air hyperventilation in adults with suspected asthma. Respiratory Medicine 1997; 91: 470-478.

Modi M, Eber E, Steinbrugger B, Weinhandl E, Zach MS. Comparing methods for assessing bronchial responsiveness in children: single step cold air challenge, multiple-step cold air challenge, and histamine provocation. Eur Respir J 1995; 8: 1742-1747.

Molphy J, Dickinson J, Hu J, Chester N, Whyte G. Prevalence of bronchoconstriction induced by eucapnic hyperpnoea in recreationally active individuals. J Asthma Early Online, 2013; 1-7.

Nielsen KG, Bisgaard H. Lung function response to cold air challenge in asthmatic and healthy children of 2-5 years of age. Amer J Respir Crit Care Med 2000; 161: 1805-1809.

Porsjberg C, Brannon JD. Alternatives to exercise challenge for the objective assessment of exercise-induced bronchospasm: Eucapnic voluntary hyperpnoea and the osmotic challenge tests. Breathe 2010; 7(1): 53-63.

Randolph C. Diagnostic exercise challenge. Curr Allergy Asthma Res 2011; 11: 482-490.

Roach JM, Hurwitz KM, Argyros GJ, Eliasson AH, Phillips YY. Eucapnic volunetary ventilation as a bronchoprovocation technique. Comparison with methacholine inhalation in asthmatics. Chest 1994; 105(3): 667-672.

Rundell KW, Anderson SD, Spiering BA, Judelson DA. Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes. Chest 2004; 125: 909-915.

Scharf SM, Hemier D, Walters M. Bronchial challenge with room temperature isocapnic hyperventilation. Chest 1985; 88: 586-593.

Schmekel N, Smith H-J. The diagnostic capacity of forced oscillation and forced expiratory techniques in identifying asthma by isocapnic hyperpnoea of cold air. Eur Respir J 1997; 10: 2243-2249.

Steinbrugger B, Eber E, Modl M, Weinhandl E, Zach MS. A comparison of a single-step cold-dry air challenge and a routine histamine provocation for the assessment of bronchial responsiveness in children and adolescents. Chest 1995; 108: 741-745.

Wesseling GJ, Vanderhoven-Augustin IML, Wouters EFM. Forced oscillation technique and spirometry in cold air provocation tests. Thorax 1993; 48: 254-259.

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

Spirometry is the most commonly performed (and mis-performed) pulmonary function test around the world. The apparent simplicity of spirometry is misleading since there are numerous subtleties that have a significant effect on the results.

I suspect that when the FVC is thought about it is most often considered to be an index towards the total capacity of the lung. That’s certainly true in it’s own way, but the FVC is actually a critically important factor when determining airway obstruction. I’ve had a number of reports across my desk lately where the patient had a reasonably large change in FVC when compared to their last visit but little change in FEV1, and this has made a difference in how the results are interpreted. For example:

Visit 1:	Observed:	%Predicted:	Predicted:
FVC:	4.27	87%	4.91
FEV1:	3.36	84%	3.99
FEV1/FVC:	79	96%	82

Visit 2:	Observed:	%Predicted:	Predicted:
FVC:	4.67	95%	4.91
FEV1:	3.38	85%	3.99
FEV1/FVC:	72	88%	82

Although the change in FVC is not significant by my lab’s standards (+0.40 L, +9%) and the FEV1 has hardly changed at all, the FEV1/FVC ratio has gone from being within normal limits to being under the LLN and therefore showing mild airway obstruction.

If just the flow-volume loops from each set of results was considered, there is no reason to suspect that either effort was inadequate.

The real difference is in how long the patient exhaled.

The ATS/ERS standard on spirometry testing has a number of things to say about how long the forced vital capacity effort should last.

“It is important for subjects to be verbally encouraged to continue to exhale the air at the end of the manoeuvre to obtain optimal effort…”

Having said that, one of the end-of-test criteria is:

“The volume–time curve shows no change in volume (0.025 L) for ≥1 s(econds), and the subject has tried to exhale for ≥3 s(econds) in children aged <10 yrs and for ≥6 s(econds) in subjects aged >10 yrs.”

It also says that:

“For patients with airways obstruction or older subjects, exhalation times of >6 s(econds) are frequently needed.”

But this is tempered with:

“Although subjects should be encouraged to achieve their maximal effort, they should be allowed to terminate the manoeuvre on their own at any time, especially if they are experiencing discomfort.”

I’ve visited a number of pulmonary function labs and clinics where spirometry was being performed and have seen a wide range in attitudes towards obtaining an “optimal” FVC. What I’ve most often seen is that an “optimal” FVC effort is one of those things where an experienced technician can make all the difference in the world. It takes practice to know how to “read” a patient in order to encourage their maximal effort and to know when to stop pushing them. In addition it takes a certain lack of self-consciousness (I forget which book I read this in but the instructions for technicians performing spirometry included something like “you should be embarrassed by level of clamor you make”). Most importantly though, it also takes a certain level of ruthlessness.

Even more importantly however, what I’ve seen among all levels of individuals that perform and review spirometry is a frequent lack of appreciation for the effect that FVC has on the FEV1/FVC ratio. Everyone understands FEV1 (and yes, many of the physicians and researchers I’ve known and respected have rightly said it’s all about the FEV1) but the first step towards determining the presence of airway obstruction is the FEV1/FVC ratio and there the FVC is just as important as the FEV1.

Taken individually both spirometry efforts met all of the ATS/ERS criteria for adequacy and this is one of the problems with the FVC. The order in which these kind of changes in FVC occur are always different and I’m often left wondering what the reason was. Does a decrease (or increase) in FVC actually reflect a change in the patient’s condition? Or was it more of a change in their mood? Or a change in which technician performed the test?

Currently my lab’s criteria for assessing changes in spirometry trends involve only the FEV1 and FVC individually, and not the FEV1/FVC ratio. I’m not sure this is correct but my thoughts on this keep changing depending on circumstances. Changes in the FEV1/FVC ratio are probably significant when the FVC efforts are comparable, such as when the expiratory time is essentially the same, but maybe not so much when the expiratory times are different. But for many COPD the differences in a patient’s expiratory time (and FVC) are often a better reflection of how well they are doing than the changes in their FEV1. And for many patients with pulmonary fibrosis, the expiratory time (even when it’s suboptimal) doesn’t affect FVC all that much. For a test as apparently simple as spirometry there is probably no simple answer to this problem.

FVC frequently matters as much as the FEV1 when it comes to assessing the presence of airway obstruction. Obtaining an “optimal” FVC remains as much an art as a science, however, and for this reason I suspect that mild airway obstruction is under-diagnosed. There is a lot of leeway in the ATS/ERS criteria for assessing the adequacy of the FVC but other than mandating an exhalation time longer than 6 seconds (10 seconds? 12 seconds? 15 seconds) which is not needed in the majority of patients, it’s unclear to me how they can be improved, particularly since this is an area where the experience of the participants (both patient and technician) often make the most difference.

References:

Brusasco V, Crapo R, Viegi G. ATS/ERS Task Force: Standardisation of lung function testing. Standardisation of spirometry. Eur Respir J 2005; 26: 319-338.

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

Recently a rather eminent reader commented on an older blog entry. He finished his comment with a paragraph on another topic, however. Specifically:

By the way, it is also high time that we scuttle the habit of expressing a measurement as percent of predicted. As Sobol wrote [5]: “It implies that all functions in pulmonary physiology have a variance around the predicted, which is a fixed per cent of predicted. Nowhere else in medicine is such a naive view taken of the limit of normal.”

I understand the point and have been thinking about this off and on since the comment was posted but I keep coming back to the same response, and that is “yes, but…”.

First the “yes” part.

Other than the fact that any percent of predicted cutoff is an arbitrary line in the sand (80% of predicted is most commonly used as the cutoff for normalacy but why not 75%? why not 85%?) the biggest argument against the use of percent predicted is the way in which normal values tend to be distributed. When FVC or TLC is studied within a reasonably large group of “normal” individuals the results are usually distributed fairly evenly above and below the mean. This is referred to as a homoscedastic distribution.

For this reason when, for example, +/- 20% is used as the normal range this tends to exclude some normal individuals with lower volumes and heights and includes some individuals with larger volumes and heights that are probably not normal.

In fact a homoscedastic distribution is much better characterized by the standard deviation of the group and more specifically, +/- 2 standard deviations.

It would therefore appear that the normal range would be more closely related to standard deviation (or other statistical value) than the percent predicted. This however, is where we get to the “but” part.

I am not a statistician and probably know just enough about statistics to get myself into trouble, but the first problem I have with this is that it assumes that the normal population is truly homoscedastic. The NHANESIII study is well known both due to both the size of the population it studied and to its sophisticated statistical analysis. It includes reference equations for both mean and LLN values. When FVC is plotted as a function of height, it becomes clear that the difference between the mean and LLN values are not constant, which would be the case if they were a function of the standard deviation, but instead vary steadily over the normal height range. This doesn’t mean that the NHANESIII LLN isn’t accurate but it does imply that the data set isn’t completely homoscedastic.

The second problem I have is that the concept of the LLN as it is usually applied also has some arbitrary elements. When a study population has a Gaussian distribution (bell-shaped curve), by definition 95% of the normal values fit within +/- 2 standard deviations.

Because the remaining 5% is much more widely spread out it has been generally decided that a function that consists of 95% of the population is likely the best description of normalacy. That’s a fairly reasonable line in the sand (although in its way just as arbitrary as an 80% cutoff) but for values like FVC and FEV1, results that are above +2 standard deviations are considered to be normal, not abnormal. As one study somewhat succinctly stated:

“Since the upper limits are not relevant in clinical spirometry, the 5% error can be transferred…”

For this reason, it is the bottom 5% of the population that is considered “abnormal” and although the LLN is calculated from the standard deviation (or the standard estimate of error, SEE, which is mathematically related to SD), it is a factor less than 2 (usually 1.645).

Part of the arbitrariness of this is that at first glance the decision to consider the bottom 5% abnormal makes sense when applied to FVC and FEV1 because reductions in these values are usually indications of one lung disorder or another and therefore elevated values are “normal”. This may well be true (and probably is) but it’s really just an assumption because I’ve never seen a single study of individuals with elevated FVC’s and FEV1’s and for this reason it’s not possible to say that there isn’t some pathology associated with elevated values.

Note: I see FVC and FEV1 results that are 130% to 140% of predicted at least a couple times a month. If this was simply a scaling issue I’d assume that the functional gas exchange surface area would scale with it but when DLCO is also measured I often find it to be normal (often with a reduced or low normal DL/VA) instead of being elevated as well. This may not be considered to be pathological but what combination of anatomy and physiology is causing lung volume and airway diameter to increase without increasing functional surface area?

For values like TLC and RV however, there are lung disorders associated with both elevated and reduced results and for this reason, reference equations usually include an upper limit of normal as well as a lower limit of normal. So, who’s (arbitrarily) deciding which values should have only a LLN and which should have an ULN and LLN? And which of these models applies to DLCO?

Finally, both the mean and standard deviation and therefore what is considered normal are dependent on the makeup of the population being studied. As an example, what if a group of Olympic athletes were studied? Using the above statistical assumptions 5% of them (and probably most of the rest of us) would have to be considered abnormal. This isn’t really true however, and points out at least one limitation to a purely statistical approach to defining normalacy.

More importantly however, this is where ethnicity comes into play. The differences between ethnicities often place one well outside the normal limits of another and this is the elephant in the room when pulmonary function statistics are discussed. There has yet to be a workable definition of what constitutes ethnicity and the selection of which one applies to a given individual has significant implications for the interpretation of their test results but is often arbitrary.

Statistical analysis is also dependent on which values are selected for analysis and I think that the apparent differences between ethnicities is exacerbated by the continued insistence on using standing height as a primary factor when analyzing pulmonary function results. Yes there is a relationship between height, lung volume and airway diameter but it is well known to be only approximate. Sitting height, for example, has been shown to be at least slightly more accurate than standing height but when was the last time you saw it used in a population study? There are probably other anthropometric measurements (or combinations of measurements) that are likely better than standing height but there has been remarkably little research in this direction.

So what does this all mean? Yes, using a fixed percentage of some kind as the cutoff for normalacy is likely inaccurate; partly because it does not accurately reflect the probable distribution of normal values and partly because any fixed percentage is arbitrary. Yes, a statistically defined LLN is more likely correct; partly because it more accurately reflects the distribution of normal values and partly there is better evidence that the normal range it describes is clinically relevant.

But the LLN also has its share of arbitrary elements and is also limited by the population being studied and the values used in analysis. In addition an 80% cutoff isn’t quite as horribly inaccurate as it is often portrayed and in instances where there are limitations in population studies and their reference equations (notably lung volumes and DLCO) it’s not as evident as it might be that the LLN is superior.

The ATS/ERS currently recommends using the LLN as the cutoff for normalacy. When reference equations come from studies with large populations and good statistical analysis this makes sense. When reference equations are from more limited studies however, the advantage of an LLN over an 80% cutoff isn’t quite as clear as many statisticians would like you to believe. Ethnicity remains the elephant in the room however, and until such time as reference equations are developed that are not dependent on ethnicity the differences between study populations often overshadows the differences between fixed cutoffs and the LLN.

So, yes, but….

References:

Aggarwal AN, Gupta D, Behera D, Jindal SK. Comparison of fixed percentage method and lower confidence limits for defining limits of normality for interpretation of spirometry. Respir Care 2006; 51(7): 737-743.

Culver BH. How should the lower limit of the normal range be defined? Respir Care 2012; 57(1): 136-143.

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.

Sobol BJ, Weinheimer B. Assessment of ventilatory abnormality in the asymptomatic subject: an exercise in futility. Thorax 1966; 21: 445-449.

Sobol BJ, Sobol PG. Editorial. Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach. Thorax 1979; 34: 1-3.

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

There has been a fair amount of confusion about PFT lab staff licensure requirements. This information is not available on the AARC website, nor on any of the AARC state society websites. A month or so ago I reached out to all of the AARC state societies but received responses from only a handful of them. I was recently able to complete this research however, by visiting the websites of the remaining state licensing boards and state legislatures.

It turns out that the majority of states require licensure of PFT Lab staff, most often by requiring CRT or RRT credentials, occasionally by allowing CPFT and RPFT credentials and in a couple of cases, a state licensure exam. There were also a couple of cases where the regulations were so vaguely written that it wasn’t clear whether pulmonary function testing fell under the Respiratory Care practitioner scope of practice or not.

Anyway, based on state society feedback and my best interpretation of the relevant laws and regulations, the following list should be a reasonably accurate look at the licensure requirements for each state.

State:	Requires Licensure:	Credentials:	Source:
Alabama	Yes	CRT, RRT	Link
Alaska	No
Arizona	Yes	CPFT, RPFT, CRT, RRT	Link
Arkansas	No		Link
California	Yes	State licensure exam	Link
Colorado	Yes	CPFT, RPFT, CRT, RRT	Link
Connecticut	Yes	CRT, RRT	Link
Delaware	Yes	CRT, RRT	Link
Florida	Yes	CRT, RRT	Link
Georgia	Yes	CPFT, RPFT	Link
Hawaii	Yes	CRT, RRT	Link
Idaho	No		Email
Illinois	Yes	CPFT, RPFT, CRT, RRT	Link
Indiana	Yes	CRT, RRT	Email
Iowa	Yes	CPFT, RPFT, CRT, RRT	Link
Kansas	No		Link
Kentucky	No		Link
Louisiana	Yes	CRT, RRT	Link
Maine	No		Email
Massachusetts	No		Link
Maryland/DC	Maybe		Link, Link
Michigan	Yes	CPFT, RPFT	Link
Minnesota	No		Email
Mississippi	Yes	CRT, RTT	Email
Missouri	Yes	CRT, RRT	Link
Montana	Yes	CPFT, RPFT, CRT, RRT	Link
Nebraska	Yes	CRT, RRT	Link
New Hampshire	Yes	CRT, RRT	Link
New Jersey	Yes	CRT, RRT	Link
New Mexico	Yes	CRT, RRT	Link
New York	Yes	CRT, RRT	Email
Nevada	Yes	CRT, RRT	Link
North Carolina	Yes	CRT, RRT	Email
North Dakota	Yes	CRT, RRT	Email
Ohio	Yes	CRT, RRT	Link
Oklahoma	Yes	CRT, RRT	Link
Oregon	No		Link
Pennsylvania	Yes	CRT, RRT	Link
Rhode Island	Probably Not		Link
South Carolina	Yes	CRT, RRT	Link
South Dakota	Yes	CRT, RRT	Link
Tennessee	Yes	CRT, RRT	Link
Texas	Yes	CRT, RRT	Link
Utah	Yes	CRT, RRT	Link
Vermont	Yes	CRT, RRT	Link
Virginia	Maybe		Link
Washington	Yes	State licensure exam	Link
West Virginia	Yes	CRT, RRT	Link
Wisconsin	Yes	Up to hospital	Email
Wyoming	Yes	CRT, RRT	Link

I have mixed feelings on the subject of licensure. On the one hand my concerns about the level of professionalism in pulmonary function testing (discussed previously) has caused my views to evolve substantially over the last couple of years. I now believe that licensure can and should be a step towards improving the quality of PFT lab staff and testing. Having said that I am extremely disappointed by how few states recognize CPFT and RPFT certification as the most appropriate requirement.

I noticed that the respiratory therapist scope of practice from many different states had mostly the same statements. The AARC has been the state (and national) level advocate for the profession and is likely responsible for this. I’m not necessarily going to blame the AARC, instead I am going to say that it appears that pulmonary function lab staff are remarkably poor advocates for our field.

There’s a lot that needs to fixed in the field of pulmonary function testing if it is going to in any way remain relevant. Going forward I’d like to suggest that even though it isn’t a requirement, all PFT labs should require their staff to obtain, at a minimum, CPFT certification. I’d also like to suggest that we all need to contact our AARC state-level political advocates and lobby for language in the respiratory therapy scope of practice statements that acknowledges the need for CPFT and RPFT certification for performing pulmonary function testing. The reality is that we can’t expect others to fix this for us. We need to advocate for ourselves.

Finally, kudos to the AARC state societies that responded to my questions and knew whether or not licensure was required (or at least acknowledged that they didn’t know). Dingbats to those that didn’t.

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

Outside the pulmonary lab there is this notion that spirometry is supposed to be so easy that anyone can do it. You just tell the patient to take a deep breath in and blow out fast and to keep blowing until they’re empty. What’s so hard about that?

Sheesh. GIGO. I keep finding ways in which the patient, their physiology and our equipment can conspire in ways to produce errors that even experienced technicians can miss. I’ve been paying a lot of attention to flow-volume loops lately and maybe it’s for this reason that I’ve seen a steady stream of spirometry tests that have something wrong with the FVC volume.

What I’ve been seeing are flow-volume loops where the end of exhalation is to the left of either the start of the FVC inhalation or of the tidal loop. Taken at face value this means that the patient did not exhale as much as they inhaled (and that the FVC is therefore underestimated) but there are several reasons why this happens and it takes a bit of detective work to figure out the cause and what to do about it.

The simplest reason is a short expiratory time. Flow-volume loops however, do not show time, only flow and volume. Sometimes when a patient stops exhaling abruptly it’s easy to see that the effort is short.

Other times it isn’t as clear:

and you need to look at the volume-time curve as well.

In some ways this is both the easiest and hardest error to correct. The simple fix is to get the patient to exhale longer, but many patients can not or will not do this no matter how many times you try. Frequently it’s because the patient is SOB or just not feeling well. Sometimes it’s due to language or cultural barriers. Sometimes it’s just because the patient doesn’t “get it”. Surprisingly enough (for my lab at least) I’d say that a lack of cooperation is in a distant last place as a cause and this is probably because we mostly see outpatients and if they don’t want to do the tests, they don’t show up.

Another reason that the FVC can be underestimated is gas trapping. Gas trapping is usually seen with severe airway obstruction but this patient had an FEV1 that was within normal limits and their FEV1/FVC ratio was only slightly below the LLN.

And the expiratory time was adequate.

One clue that this is gas trapping and not something else is that the tidal loop overlaps itself reasonably well and is not obviously drifting to either the left or the right. When our lab software displays a volume-time curve it does not show more than one second of data before the start of the FVC effort. Fortunately, I can download the raw test data and re-graph it using a spreadsheet and when this is done, it can be seen that the patient was unable to return to the tidal baseline with the FVC effort.

There is no “fix” for gas trapping. Some investigators have proposed that after the initial blast (presumably including the peak flow and FEV1) patients should be told to relax their effort while continuing to exhale and that this will allow a larger FVC volume to be measured. To my knowledge this has not been formally studied so any improvement in FVC volume would be conjectural. In addition the difference between an FVC effort that is forced throughout the maneuver versus one that is only forced at the beginning is a distinction that many patients may not be able to make.

Finally, my lab has a mix of different test systems. Some are simple pneumotach spirometry systems, some are plethysmograph systems with pneumotachs and pressure-actuated valves, and some are volume displacement spirometry systems with pressure-actuated valves. For all of these systems either the patient or the system itself can leak.

The easiest way to see a leak is to notice whether or not the tidal loop is drifting but in this case the patient only had one tidal breath before starting the FVC maneuver. The patient’s FEV1 and PEF were above normal so gas trapping is unlikely. They also exhaled for a reasonable period of time.

This means that a leak is really the only possibility. Once it’s detected a leak should be fixed before any further testing is performed. Yes, this means that testing needs to be put on hold until this is done but continuing to perform tests while knowing there is a leak is just not acceptable in any way.

So, simple stuff, yes? But the reason I selected these specific examples was that in every case the technician performing the test wrote “good test quality” in the notes. This can probably be excused for the patient with gas trapping since in every other way the test effort met the criteria for acceptability. But the others? Not so much.

All of the technicians in my lab have a minimum of two years of experience, and in several cases quite a few more. So why did they miss these things? In each case the primary clue that the FVC was being underestimated was because the end of exhalation of the FVC maneuver was at a lower volume (further to the left) than the tidal loops. So I think it is largely because everybody (and I’ve seen this in other labs than my own) tends to ignore tidal loops. I suspect that the most common thought is that tidal loops are just something that happens before the FVC maneuver so of course they aren’t really important.

There is also nothing in the ATS/ERS spirometry standards that specifically addresses tidal loops. To a large extent I can understand this since the standards are primarily designed to address the actual FVC, SVC and MVV test maneuvers. Even so, the standards include several graphs that show the tidal breathing prior to the maneuver and it is evident that it is assumed to be stable and not drifting in any way. For this reason I think that the next time the ATS/ERS spirometry standards are updated it wouldn’t hurt to define the acceptable limits on any drift during tidal breathing.

Finally, I’ve seen some test system software that did not allow tidal loops to be displayed. In some cases this was just in the manufacturer’s sales literature so it may actually be possible to override this. Even so tidal breathing is part of the FVC maneuver and because it can provide important clues on expiratory time, gas trapping and leaks it should always be included when flow-volume loops are displayed.

The “simple” FVC maneuver has numerous subtleties and it’s a harder test to perform correctly than may appear at first glance. We’re not going to stop spirometry from being performed outside the pulmonary lab (nor should we even try) but if we’re going to show why pulmonary labs continue to be needed then we’re going to have to make sure that we perform spirometry better than anybody else. In particular that means we need to understand and pay attention to all of the details and for spirometry that includes the tidal loops.

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

When Tiffeneau described the FEV1 in 1947 and Gaensler the timed FVC and FEV1/FVC ratio in 1950 this opened up an entirely new territory for pulmonary investigators to explore. Numerous new measurements were rapidly mapped out with often conflicting titles. The situation became confusing enough that the British Thoracic Society met in 1956 specifically to standardize terminology. At this time only the volume-time curve was available for measurement purposes (usually a pen trace on kymograph paper) and this fact helped determine what measurements it was possible for researchers to make.

These measurements were in somewhat common use for the first decades of modern spirometry. They have since mostly passed into disuse and have largely been forgotten either because they were superceded by the flow-volume loop or because they never established any particular clinical value. Even so most of these measurements are included as reporting options in current spirometry testing systems. Despite being of questionable value they are still interesting if for no other reason than that they highlight the incredible number of ways that a volume-time curve can be analyzed.

FEV_0.5

In retrospect the use of the FEV1 and FEV1/FVC ratio to assess airway function seems inevitable but in the early decades it wasn’t clear what timed measurements were optimal. Like the FEV1 the forced expired volume in 0.5 seconds can be measured from the volume-time curve. The FEV_0.5 is considered more reproducible than the Peak Expiratory Flow and has been used to assess cough. Although normal values for the FEV_0.5 were included in the reference equations from the 1961 VA-Army and Kunudson’s 1976 spirometry study this measurement has rarely been used in adults but has instead found extensive use when measuring and reporting spirometry in infants and children.

FEV_0.75

The FEV_0.75 appears to have been used primarily in Britain and Europe. Interestingly it (multiplied x 40) was assessed in terms of normal values for the MVV (MBC) and reference equations for the FEV_0.75 were never developed or published. It was actually used relatively rarely even through the 1970’s and was only used as recently as 2000 in a longitudinal study of Finnish smokers because the original study used the FEV_0.75.

FEV2, FEV3:

FEV2 and FEV3 have been reported occasionally in articles since the 1950’s. Although normal values for FEV2 and FEV3 were included in Knudson’s 1976 spirometry study these measurements have never been commonly used. One 2005 study proposed estimating the FVC from the FEV2 and FEV3 in cases where the expiratory effort was otherwise short. More recently the FEV3/FVC ratio has been proposed by several authors as a more accurate assessment of small airway function than the FEF25%-75% but although this idea has merit it has not yet achieved common use.

FEF200-1200:

The FEF200-1200 is the average expiratory flow rate between 0.2 and 1.2 liters of the FVC. It was considered as a substitute for Peak Flow and for many individuals there is a relatively close match between the two. Since it is measured across a specific volume however, it becomes progressively less accurate as the vital capacity becomes smaller (either normally as in short or elderly individuals or with restrictive lung disease) or in circumstances where the peak flow occurred over a particularly short interval (commonly seen in COPD).

FEF0-25%

The FEF0-25% is the average flow rate over the first 25% of the FVC. Like the FEF200-1200 is was intended to assess the maximal expiratory flow rate at high lung volumes. Although the Peak Flow usually occurs within the first 25% of the FVC, the FEF0-25% is the average flow rate over that volume, which includes the periods of accelerating and decelerating flow rates and for this reason tends to correlate relatively poorly with peak flow.

FEF75%-85%

The average flow rate from 75% to 85% of the FVC occurs at low (close to RV) lung volumes and for this reason is expected to reflect airflow from the smaller airways. Normal values were first developed by Morris et al in 1975 and were found to correlate with height, age and smoking history. Even more than the FEF25%-75% (discussed previously) however, the FEF75%-85% is highly sensitive to the FVC volume and expiratory time.

FEV10%

The average flow rate during the last 10% of the FVC. Like the FEF25%-75% this value was expected to reflect airflow from the smaller airways. It is also highly sensitive to FVC volume and expiratory time. There are no reference equations and this measurement never appeared in more than a few research articles and textbooks.

FET25%-75%

The expiratory time between 25% and 75% of the FVC. Also known as the Mid-Expiratory Time (MET), Maximal Mid-Expiratory Flow Time (MMFT) and the Maximal Mid-Expiratory Time (MMET). Although said to correlate well with respiratory resistance there are no reference equations and this measurement never appeared in more than a handful of research articles and textbooks.

FET98%

The expiratory time to 98% of the FVC. Although proposed as a standardized way to measure expiratory time it never saw common use.

There are numerous measurements that can be made from a spirometry maneuver. Simply because a measurement can be made does not mean that it is clinically significant however. In the first decades of modern spirometry many different values were proposed but only a small number of them have survived to the present time. Interestingly, many of the current spirometry systems allow many if not most of these now disused measurements to be reported. About 10 or 15 years ago my lab’s software came bundled with a report format that included almost 20 different values for a single FVC. I’ve seen this report used by at least a couple PFT labs who may have thought that more is better. I’ve also seen some of these measurements used in a variety of research studies, some old, some relatively recent. Their clinical relevance is likely small at best but although these measurements are now mostly gone they have not been completely forgotten.

References:

Hanson JE, Sun X-G, Wasserman K. Discriminating measures and normal values for expiratory obstruction. Chest 2009; 136(6): 369-377.

Ioachimescu OC., Venkateshiah SB, Kavuru MS, McCarthy K, Stoller JK. Estimating FVC from FEV2 and FEV3: Assessment of a surrogate spirometric parameter. Chest 2005; 128(3): 1274-1281.

Knudson RJ, Slatin RC, Lebowitz MD, Burrows B. The maximal expiratory flow-volume curve. Normal standards, variability and effects of age. Amer Rev Respir Dis 1976; 113: 587-600.

Kory, RC, Callahan R, Boren HG, Syner JC. The veterans administration-army cooperative study of pulmonary function I. Clinical spirometry in normal men. Amer J Med 1961; 30(2): 243-258.

Miller WF, Scacci R, Gast LR. Laboratory evaluation of Pulmonary Function, copyright 1987, published by JB Lipincott.

Morris JF, Koski A, Breese JD. Normal values and evaluation of Forced End-Expiratory Flow. Amer Rev Respir Dis 1975; 111(6): 755-762.

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

I’ve discussed the issue of inserting a predicted FVC into the predicted lung volumes several times now. At the risk of beating this issue to death I’d like to put to rest the notion that an FVC and an SVC are the same thing.

A Forced Vital Capacity (FVC) maneuver is designed to measure the maximum expiratory flow rates, in particular the expired volume in 1 second (FEV1). It has long been recognized that the effort involved in the FVC maneuver can cause early airway closure, even in individuals with normal lungs, and that for this reason the vital capacity can be underestimated due to gas trapping. This effect is usually magnified with increasing age and in individuals with obstructive lung disease.

A Slow Vital Capacity (SVC) maneuver is designed to measure the lung volume subdivisions Inspiratory Capacity (IC) and Expiratory Reserve Volume (ERV), and to maximize the measured volume of the vital capacity. Due to the more relaxed nature of the SVC maneuver there is significantly less airway closure and for this reason the SVC volume is usually larger than the FVC, again even in individuals with normal lungs.

Comparing individual reference equations can be difficult but in general the reference equations for SVC and FVC agree with this. Taking the available SVC and FVC reference equations (unfortunately limited to Caucasian because there are almost no SVC equations for other ethnicities) it is apparent that the average predicted SVC is larger than the average predicted FVC, and that the magnitude of this difference increases with age:

and that this applies to both genders:

This is also true when the predicted SVC and FVC come from the same population which is the case for references [C] and [H]:

That’s it. An SVC and an FVC are not the same thing. A predicted FVC can of course be larger than a predicted SVC but that is due to the selection of specific reference equations and does not reflect the general relationship between SVC and FVC.

I promise that as long as everybody stops thinking that a predicted FVC is somehow “better” than a predicted SVC I won’t bring this subject up again. Is it a deal?

Predicted SVC was either calculated directly or by subtracting the predicted RV from the predicted TLC. (Note: ht = height in cm).

Male	Reference	Formula
SVC	[A]	(0.073*ht)-(0.021*age)-6.866
	[C]	-5.897+(0.069*ht)-(0.023*age)
	[H]	-4.69-(0.025*age)+(6.44*(ht/100))

Male	Reference	TLC Equation	RV Equation
	[B]	(0.0795*ht)+(0.0032*age)-7.333	(0.0216*ht)+(0.0207*age)-2.84
	[K]	(0.118*ht)-13.23	(0.0197*ht)+(0.0141*age)-2.08
	[M]	(7.956*(ht/100))-6.948	(3.38*(ht/100))+(0.02*age)-(0.014*wt)-3.927
	[N]	(7.99*ht*0.01)-7.08	(0.0131*ht)+(0.022*age)-1.23

Female	Reference	Equation
SVC	[A]	(0.049*ht)-(0.023*age)-3.409
	[C]	-3.597+(0.05*ht)-(0.021*age)
	[H]	-5.49-(0.025*age)+(6.44*(ht/100))

Female	Reference	TLC Equation	RV Equation
	[B]	(0.059*ht)-4.537	(0.0197*ht)+(0.0201*age)-2.421
	[K]	(-0.0094*age)+(0.0629*ht)-4.48	(0.0259*ht)+(0.0091*age)-3.15
	[M]	(7.107*(ht/100))-6.435	(2.548*(ht/100))+(0.017*age)-3.387
	[N]	(6.6*ht*0.01)-5.79	(0.0181*ht)+(0.016*age)-2

Male	Reference	Equation
FVC	[D]	-0.1933+(0.00064*age)-(0.000269*age^2)+(0.00018642*ht^2)
	[C]	-5.473+(0.067*ht)-(0.025*age)
	[E]	-6.142-(0.0281*age)+(7*(ht/100))
	[F]	-8.7818+(0.0844*ht)-(0.0298*age)
	[G]	EXP(-10.258+2.28*LN(ht)+(0.006767*age)-(0.000124*age^2))
	[H]	-5.22-(age*0.03)+(6.73*(ht/100))
	[I]	(0.148*(ht/2.54))-(0.025*age)-4.241
	[J]	(0.138*(ht/2.54))-(0.027*age)-3.445
	[L]	(0.0517*ht)-(0.0207*age)-3.18
	[M]	(6.628*(ht/100))-(0.028*age)-5.377

Female	Reference	Equation
FVC	[D]	-0.356+(0.0187*age)-(0.000382*age^2)+(0.00014815*ht^2)
	[C]	-3.335+(0.049*ht)-(0.024*age)
	[E]	-4.04-(0.0259*age)+(5.364*(ht/100))
	[F]	-2.9001+(0.0427*ht)-(0.0174*age)
	[G]	EXP(-9.069+(2.013*LN(ht))+(0.00847*age)-(0.000155*age^2))
	[H]	-5.87-(0.03*age)+(6.73*(ht/100))
	[I]	(0.115*(ht/2.54))-(0.024*age)-2.852
	[J]	(0.114*(ht/2.54))-(0.024*age)-2.795
	[L]	(0.0441*ht)-(0.0189*age)-2.848
	[M]	(4.321*(ht/100))-(0.023*age)-2.379

References:

[A] Cordero PJ, Morales P, Benlloch E, Miravet L, Cebrian J. Static Lung Volume: Reference values from a Latin population of Spanish descent. Respiration 1999; 66: 242-250.

[B] Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volume in healthy nonsmoking adults. Bull Eur Physiopathol Respir 1983; 18: 419-425

[C] Gutierrez C, et al. Reference values of pulmonary function tests for Canadian caucasians. Can Respir J 2004; 6: 414-424.

[D] Hankinson JL, Odencrantz JR, Fedan, KB. Spirometric reference values from a sample of the general U.S. Population. Amer J Resp Crit Care 1999; 159: 179-187

[E] Johannessen A, Lehmann S, Omenaas ER, Side GE, Bakke PS, Gulsvik A. Post-bronchodilator spirometry reference values in Adults and implications for disease mangement. Amer J Resp Crit Care Med 2006; 173(12): 1316-1325

[F] Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow volume curve with growth and aging. Am Rev Resp Dis 1983; 127: 725-734

[G] Kuster SP, Kuster D, Schindler C, Rochat MK, Braun J, Held L, Brandli O. Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years. Eur Respir J 2008; 31: 860-868.

[H] Marsh S, Aldington S, Williams M, Weatherall M, Shirtcliffe P, McNaughton A, Pritchard A, Beaseley R. Complete reference ranges for pulmonary function tests from a single New Zealand population. New Zealand Med J 2006; 119: N1244.

[I] Morris JF, Koski A, Johnson LC. Spirometric standards for healthy nonsmoking adults. Am Rev Resp Dis 1971; 103: 57-67.

[J] Morris JF, Koski A, Temple WP, Claremont A, Thomas DR. Fifteen-year interval spirometric evaluation of the Oregon Predictive equations. Chest 1988; 93: 123-27

[K] Neder JA, Andreoni S, Castelo-Filho A, Nery LE. Reference values for lung function tests. I. Static Volume. Braz J Med Biol Res 1999; 32: 703-717

[L] Pereira CADC, Sato T, Rodrigues SC. New Reference Values for forced spirometry in white adults in Brazil. J Bras Pneumol 2007; 33: 397-406.

[M] Roberts CM, MacRae KD, Winning AJ, Adams L, Seed WA. Reference values and prediction equations for normal lung function in a non-smoking white urban population. Thorax 1991; 46: 643-650.

[N] Stocks J, Quanjer PH. Reference values for residual volume, function residual capacity and total lung capacity. Eur Respir J 1995; 8: 492-506.

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