Author: Richard Johnston

I was about to put a PFT report I’d been reviewing in my outbox when I noticed something odd about the flow-volume loop.

What I saw was that the final inspiration of the FVC maneuver had ended to the left of the initial inspiration. This means a couple of thing, first and foremost that the FIVC was larger than the FVC and that the FVC was likely underestimated because the patient hadn’t really taken a full inspiration prior to exhaling. I had already looked at the raw data for the patient’s spirometry results for other reasons but I pulled them up again to see if I had missed something.

What I saw was that the spirometry test with the best FVC, FEV1, PEF and expiratory time was the one that had been selected for reporting. I also saw that all of the patient’s spirometry results were fairly uniform and met the ATS/ERS requirements for repeatability. Despite the fact that the FVC in every effort was likely submaximal the patient had managed to perform the FVC maneuvers with remarkable similarity.

What I didn’t see however, was any visible indication that the FIVC was larger than the FVC (and it’s important to note that the software module I use to review spirometry results is the same that’s used to perform the test in the first place).

I had to page down a bit in the tabular results to see that yes, the FIVC was significantly larger than the FVC. In one sense this didn’t make a difference for this particular patient’s report because I had already noted that the SVC from the patient’s lung volume test was larger than the FVC and that FEV1/SVC ratio was reduced which indicated the presence of airway obstruction. The FIVC and SVC were in fact essentially identical so the FEV1/VC wasn’t going to be any different.

When I review a report that has lung volumes and/or a DLCO along with spirometry I always compared the SVC from the lung volumes and the inspired volume from the DLCO with the FVC. If either are larger than the FVC I recalculate the FEV1/VC ratio to see if it is low. Patients with airway obstruction often have a significantly larger SVC or Inspired Volume than their FVC and this is likely because of the airway compression that occurs during a forced expiratory effort that doesn’t occur during a more relaxed effort.

What I tend to forget however (and this is a good reminder), is that the FVC can also be underestimated because of a suboptimal inspiration. Detecting an inadequate inspiratory effort tends to be difficult because there usually isn’t any good indication that it is happening. To some extent you can tell through body language or from irreproducible results that a patient isn’t inhaling correctly but unlike a suboptimal expiration there are no objective criteria for a suboptimal inspiration. In this patient’s case because their flow-volume loops, volume-time curves and numerical results all met quality and repeatability criteria there was no particular indication at all that the inspiration was lower than it should have been.

What is important about all this is that when I review the patient’s raw spirometry test data (and more importantly when the test is being performed) it is very difficult to see that the FIVC is larger than the FVC. This is because all of the inspiratory flow-volume loop and volume-time data are cut off at the point of the initial peak inspiration for the FVC effort. Why is this happening? Strictly speaking this is a decision made by a programmer or other software designer and not from anything in the ATS/ERS standards for spirometry, so the blame, if there is any, can be placed on the manufacturer of our test equipment.

Why did the larger inspiratory effort show up on the report but not when I reviewed the raw spirometry data? Maybe there were different design specifications, or maybe because of an oversight, or because the graph software was written by a different programmer or maybe even because of sloppy programming. Regardless of the reason it was fortuitous because otherwise I wouldn’t have noticed it at all. But this also points out a blind spot we may all have. Look in any textbook or journal article and you will see that it is a standard convention that the position of the flow-volume loop in its graph is always determined by the initial inspiratory effort and not by any subsequent inhalation. This is probably a mistake on our part.

The ATS/ERS recommendation is to use the largest VC, regardless of the source, when calculating the FEV1/VC ratio. For this reason, the maximal flow-volume loop should be positioned on its graph relative to the largest inspiration, not the initial inspiration. If this was done, the flow-volume loop for this patient would have looked like this:

When displayed this way it would have been immediately evident that the initial inspiration was inadequate and for this reason it would be my recommendation that this should be the standard approach for graphing flow-volume loops. This may be a problem unique to the manufacturer of my lab’s test equipment but I’d be willing to bet it isn’t. I don’t have access to any other manufacturer’s test equipment so I can’t verify this in any way but since “everybody” knows how flow-volume loops are “supposed” to be graphed I’d be inclined to guess it’s pretty universal.

We have a limited amount of space on our reports and there are many spirometry values we don’t report both for the sake of clarity and the sake of brevity. FIVC is not a value we report and in fact we look at it only rarely. This is due to the fact that almost always the FIVC is less than or at best equal to the FVC so it doesn’t seem like it’s particularly important. This doesn’t mean that an FIVC can’t be an important clue when assessing spirometry test quality. It also doesn’t means that the FIVC should be overlooked when searching for the largest VC for the FEV1/VC ratio. Most importantly though, it means that the FIVC shouldn’t be hidden by artificially limiting how much of it is displayed on a flow-volume loop when it is being reviewed and most particularly when the test is being performed.

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

Recently I was discussing a flow-volume loop with one of our pulmonary physicians. His concern was whether the loop, which was from a patient with a cracked hyoid, was showing inspiratory obstruction or not. I had to point out that the inspiratory flows on the loop in question came from the pre-FVC inspiration that started at FRC, not RV, and that we don’t emphasize maximal inspiratory flow at that point in the test, just maximal inspiratory volume and for these reasons the flow-volume loop was not a reliable indicator of inspiratory obstruction.

When we assess flow-volume loops we usually don’t pay a lot of attention to the inspiratory loops from routine spirometry and this is because they aren’t terribly reliable. As with all routine spirometry there are going to be issues with patient performance. Many patients have difficulty performing a maximal inspiratory flow maneuver because they don’t “get it” or will come off the mouthpiece as soon as they have finished exhaling despite repeated coaching. In other instances we have enough problems getting a good expiratory maneuver without even trying to worry about any kind of an inspiratory effort.

More importantly however, is that even when we are able get a patient to perform an adequate inspiratory maneuver we have to report a given spirometry effort based on its maximal expiratory values, not the inspiratory values. Our lab software allows us to mix-and-match expiratory values like FVC, FEV1 and the flow-volume loop from different spirometry efforts but it does not allow us to take the best inspiratory values from one spirometry effort and match them with the best expiratory values from another test. This means that the only time a patient’s best inspiratory values can be reported is when they coincidentally also belong to a spirometry effort with the best expiratory values.

Note: I will mention in passing that the DOS version of our lab software that we used over 15 years ago allowed us to mix-and-match inspiratory and expiratory values from different spirometry efforts. This feature (along with several other useful features) didn’t make the transition to the Windows version of the software. Progress isn’t always progress!

What this means is that if we took the inspiratory flow-volume loops from routine spirometry at face value we would be reporting a lot of false-positives for inspiratory airway obstruction. Our work-around for this problem is to ask our pulmonary physicians to specifically request an inspiratory flow-volume loop when they suspect inspiratory airway obstruction. This allows us to focus on obtaining and selecting the best inspiratory effort without worrying about the expiratory values or at least to separate the tests where we emphasize one feature over another.

When we do attempt to obtain an inspiratory FVL it is easy to reject a clearly suboptimal maneuver but at what point is an inspiratory effort acceptable? Interestingly, although the ATS/ERS Standards for Spirometry states that the expiratory effort of an FVC maneuver should be

“followed by a rapid full inspiration with maximum effort back to TLC”

it does not indicate how to assess the quality or reproducibility of the inspiratory maneuver. In fact, other than noting that MIF mean Maximal Inspiratory Flow the ATS/ER Spirometry Standards do not discuss any of the instantaneous flow measurements (MIF25%, MIF50%, MIF75%, MEF25%, MEF50% and MEF75%). There is some discussion on the use of the inspiratory flow-volume loop in the ATS/ERS Statement on Interpretation but the only reference to quality assessment is

“It is critical that the patient’s inspiratory and expiratory efforts are near maximal and the technician should confirm this in the quality notes.”

I guess this is a “we’ll know it when we see it” type of thing since otherwise the criteria by which the maximal inspiratory flow and maximal inspiratory volume are determined remain unclear.

Once you have an inspiratory flow-volume loop with (presumably) good quality however, it is the contour that is usually most informative.

Contour is one of those things where everybody “knows” what inspiratory obstruction looks like but is difficult to describe otherwise. The measured values that have been used most often to describe inspiratory obstruction are the Maximal Inspiratory Flow rate at 50% of the vital capacity (MIF50%) and the ratio between the Maximal Expiratory and Inspiratory Flow rates at 50% of the vital capacity (MEF50%/MIF50% ratio).

Note: The average flow between 25% and 75% of the FIVC (the FIF25%-75%) and the Forced Inspired Volume in 1 second (FIV1) have also been suggested as also being sensitive to inspiratory obstruction but no thresholds or LLN’s have been proposed for them.

There is a general consensus that inspiratory obstruction is present when:

MIF50% < 100 LPM (1.67 L/sec)

MEF50%/MIF50% > 1.0

but other than the fact that these values come from a single study performed in 1975 and have been copied verbatim by most subsequent studies there are at least a couple problems with these values.

As already mentioned the best MIF50% and MEF50% may come from different spirometry efforts. One study showed that almost two-thirds of the time the highest PIF and MIF50% occurred in a different spirometry effort than the one selected for best expiratory values. Another study showed that in a population of patients with inspiratory obstruction the MEF50%/MIF50% ratio decreased from 3.07 to 1.77 when the spirometry effort with the best combined MIF50% and MEF50% was selected rather than the best FVC and FEV1. For this reason when inspiratory obstruction is being evaluated it is apparent that the spirometry selection criteria needs to be different than that used for normal spirometry. One study proposed that the inspiratory effort with the best FIVC + MIF50% + PIF should be selected for reporting and in the absence of an official ATS/ERS statement this appears to be a useful set of criteria.

The usefulness of the MEF50%/MIF50% ratio however, also presumes that the MEF50% is relatively normal but the MEF50% will be reduced when airway obstruction (i.e. Asthma, COPD) is present. MIF50% also tends to decreases when airway obstruction is present but even so the MEF50%/MIF50% ratio will be tend to be lower than it “should be” even when inspiratory obstruction is also present.

Next, MIF50% and MEF50% should be measured at 50% of the vital capacity, but which vital capacity? Exhaled or inhaled? Relating inspiratory flow to the exhaled vital capacity probably makes the most sense and a review of the literature indicates that this is the most common (but interestingly not completely universal) approach but when I checked our lab software I found that it was measuring the MIF50% using the inspired vital capacity and the MEF50% using the exhaled vital capacity. As well as making the MIF50% questionable this also calls into question the validity of the reported MEF50%/MIF50% ratio in our and possibly other test systems.

An additional point to this is that as already mentioned the ATS/ERS Standard for Spirometry states that the inspiratory effort should follow the expiratory effort. At least one study showed that FIVC, MIF50% and PIF were larger when the inspiratory effort preceded the expiratory effort or was performed separately. This is not an option for us since my lab’s software will only calculate the MIF, PIF and FIVC values when the inspiratory effort follows the FVC maneuver.

Despite their importance, inspiratory flow rate have been studied almost exclusively by comparing different groups of patients with each other. There are very few reference equations to aid in determining normal ranges.

Reference:	Value:	Gender:	Age:	Equation:
[A]	MIF50%	Male	21-75	(1.07 x BSA) – (0.20 x age) + 2.78
[A]	PIF	Male	21-75	(1.15 x BSA) – (0.14 x age) + 2.73
[B]	FIV1/FIVC	Male	18-34	77.4 + (7.7 x Ht(M)) – (0.04 x age)
[B]	FIV1/FIVC	Male	35-73	107.9 – (3.4 x Ht(M)) – (0.26 x age)
[B]	FIV1/FIVC	Female	18-34	60.8 + (20.6 x Ht(M)) – (0.28 x age)
[B]	FIV1/FIVC	Female	35-73	121.6 – (14.1 x Ht(M)) – (0.29 x age)

Probably the biggest problem with using numerical values to assess inspiratory obstruction is that only a small number of patients that meet these criteria actually have upper airway obstruction. One study that evaluated these criteria showed that of 40 patient with a MIF50% < 100 LPM only 3 (7.5%) actually had upper airway obstruction and that of 207 patient with a MEF50%/MIF50% ratio > 1.0 (and <0.3) only 17 (8.2%) had upper airway obstruction.

On the other hand the same study showed that 100% of the patients with a visually abnormal inspiratory flow-volume loop had upper airway obstruction. For this reason, it seems that we really do know upper airway obstruction when we see it and that the contour of the inspiratory flow-volume loop remains the best tool for determining its presence.

The inspiratory flow-volume loop is an important tool for determining the presence of both fixed and variable upper airway obstruction during inspiration. This kind of obstruction can be a result of subglottic stenosis, goiter, Parkinson’s disease, Sarcoidosis, Wegener’s granulamatosis, vocal cord dysfunction, tumors and obstructive sleep apnea. Although numerical analysis of inspiratory flow rates can raise the suspicion of upper airway obstruction visual inspection of the flow-volume loop remains the most accurate approach to assessing test results.

Although inspiratory obstruction is admittedly far less common than expiratory obstruction I’d like to see some acknowledgment from equipment manufacturers that the criteria for selecting an inspiratory flow-volume loop are quite different and possibly in conflict with the selection criteria and possibly even the test procedure for the FVC and FEV1. The ability to mix-and-match inspiratory and expiratory efforts would go a long way towards correcting this problem. I’d like to see the ATS/ERS publish standards for the performance of an FIVC maneuver and indications on how to assess quality and repeatability. I’d also like to see further work on characterizing normal inspiratory flow rates (the FIF25-75 in particular looks interesting and deserves further study) and their LLN because otherwise we are mostly flying by the seat of our pants when we use just the contour of the inspiratory flow-volume loop to diagnose inspiratory airway obstruction.

References:

[A] Bass H. The flow volume loop: Normal standards and abnormalities in Chronic Obstructive Pulmonary Disease. Chest 1973; 63: 171-176.

Brusasco V, Crapo R, Viegi G. ATS/ERS Task Force: Standardisation of Lung Function Testing. Standarisatio of spirometry. Eur Respir J 2005; 26: 319-338.

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

Ewald FW, Tenholder MF, Waller RF. Analysis of the inspiratory flow-volume curve. Should it always preced the forced expiratory maneuver. Chest 1994; 106: 814-818.

[B] Gulsvik A, Tosteson T, Bakke P, Humerfelt S, Weiss ST, Speizer FE. Expiratory and inspiratory forced vital capacity and one-second forced volume in asymptomatic never-smokers in Norway. Clin Physiology 2001; 21(6): 648-660.

Hnafiuk OW, Slade AR. Characterization of the inspiratory flow-volume curve in asymptomatic patients with no known pulmonary disease and normal expiratory spirometry. Chest 1995; 108(3): S187.

Jordanoglou J, Pride NB. A comparison of maximum inspiratory and expiratory flow in health and in lung disease. Thorax 1968; 23: 38-45.

Masumi S, Nishigawa K, Williams AJ, Yan-Go FL, Clark GT. Effect of jaw position and posture on forced inspiratory airflow in normal subjects and patients with obstructive sleep apnea. Chest 1996; 109: 1484-1489.

Modrykamien AM, Gudavalli R, McCarthy K, Liu X, Stoller JK. Detection of upper airway obstruction with spirometry results and the flow-volume loop: A comparison of quantitative and visual inspection criteria. Resp Care 2009; 54(4): 474-479.

Reddy R, Cook T, Tenholder MF. Bronchodilation and the inspiratory flow-volume curve. Chest 1996; 110: 1226-1228.

Rotman HH, Liss HP, Weg JG. Diagnosis of upper airway obstruction by pulmonary function testing. Chest 1975; 68: 796-799.

Sterner JB, Morris MJ, Sill JM, Hayes JA. Inspiratory flow-volume curve exaluation for detecting upper airway disease. Resp Care 2009; 54(4): 461-466.

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

Recently I was reviewing a cardio-pulmonary exercise test (CPET) that at first glance seemed to show the patient had a pulmonary mechanical limitation. Specifically, the patient’s minute ventilation (Ve) at peak exercise was 93% of predicted. This was something you’d expect if a patient had an obstructive or restrictive lung disease but I could see right away that the patient’s baseline pulmonary function tests were actually pretty normal.

The maximum oxygen consumption was 73% of predicted so it was apparent the patient had an exercise limitation of some kind but based on a number of other factors I didn’t think it had anything to do with the mechanical aspects of the patient’s lung.

The first question that should always be asked when looking at a CPET report is whether the test was adequate or not. Although in this case the elevated minute ventilation by itself says it was, the patient’s maximum heart rate was also 102% of predicted (our threshold is 85%) and the RER at peak exercise was 1.12 (our threshold is 1.10) so it was apparent that the patient had given a good exercise test effort.

Once you get past adequacy, there are a number of odd aspects to this CPET. When looking at the ventilation data, the elevated minute ventilation (93% of predicted) and respiratory rate (65 breaths/min) at peak exercise would be something you’d expect to see in a patient with a restrictive lung disease. The patient’s TLC was normal however and in addition the Tidal Volume/Inspiratory Capacity ratio (Vt/IC) at peak exercise was only 0.72. Patients with restrictive (and obstructive) lung diseases tend to have high Vt/IC ratios, with values above 0.90 not being particularly unusual. In this case, the Vt/IC ratio of 0.72 is normal and also says that the patient still had reserves in their tidal volume available to them at that point.

So what was driving the patient’s ventilation so high? Ventilation is usually driven by arterial carbon dioxide (PaCO2) and pH. My lab only does non-invasive exercise testing so we don’t insert arterial lines or perform arterial punctures in order to get blood gases. For this reason we rely heavily on the ventilatory equivalents, and in particular the relationship between Ve and VCO2. There are several different ways to look at these values (Ve/VCO2 at AT, lowest observed Ve/VCO2, Ve-VCO2 slope to AT and Ve-VCO2 slope to peak exercise) and we report all of them. This may appear to be overkill but even though many studies have shown both the value and the power of the Ve-VCO2 relationship there is a great deal of contradictory information about which specific relationship is most informative. I keep hoping to be able to simplify this at some point but until that time I feel it is better to report all of the Ve-VCO2 values rather try to guess which is most relevant. In this patient’s case, all values were mildly abnormal:

An elevated Ve-VCO2 is usually a strong indication of a problem with gas exchange. For this reason it is seen in obstructive lung diseases like COPD and restrictive lung diseases like pulmonary fibrosis. It is also seen however in cardiovascular diseases and this is because even mildly elevated pulmonary arterial pressures can cause micro-fracturing and micro-scarring of the pulmonary vasculature. When this happens, DLCO can remain more or less normal for prolonged periods of time but DLCO is performed at rest and does not predict gas exchange during exercise. When cardiac output increases during exercise the pulmonary capillary blood volume usually increases as well which acts to improve overall lung perfusion and ventilation-perfusion matching. A consequence of pulmonary vascular disease is therefore not only an elevated ventilation-perfusion mismatching at rest but an inability to increase pulmonary capillary blood volume during exercise.

The primary clue that this patient’s problem is probably cardiovascular in nature is their VO2 at AT, which is only 30% of the predicted maximum. The LLN for this patient’s age and sex is 44%, so they are well below normal. A low VO2 at AT is an indication of a low cardiac output or at least a diminished ability to get oxygen to the exercising muscles. Seconding this is the fact that despite indications of pulmonary vascular disease the patient did not desaturate (i.e. their SpO2 remained normal). SaO2 will remain normal even if gas exchange poor when the cardiac output is decreased by an equivalent (or greater) amount.

Finally, the Ve at AT was only 25% of the predicted maximum. At least one study has shown that when a true pulmonary mechanical limitation is present the Ve at AT will be elevated as well and for this reason we use a Ve at AT above 42% as an indicator for this.

Despite having a maximum minute ventilation of 93% of predicted, this patient’s problem was not really due to a pulmonary mechanical limitation. When patients have obstructive or restrictive lung diseases their predicted maximum minute ventilation is usually decreased as well. This patient’s predicted maximum Ve was reasonably normal but their ventilation is being driven to excessively high values probably due to a combination of ventilation-perfusion mismatching and a diminished cardiac output.

Exercise limitation is often multi-factorial. In the very strictest sense of the term this patient did have a pulmonary mechanical limitation but in this case the fact that it existed at all was likely due to a combination of pulmonary vascular and cardiovascular disease and not to a defect in the patient’s ventilation.

References:

Medoff BD, Oelberg DA, Kanarek DJ, Systrom DM. Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from a cardiovascular limit to exercise. Chest 1998; 113: 913-918.

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

This is one of my pet peeves. It started for me back in the 1970’s when the Intensive Care Units where I was working were evaluating thermal dilution cardiac output meters. This was at a time when digital displays were just starting to become common. One of the meters showed cardiac output with two digits after the decimal point (i.e. 0.12) and the other one had three digits after the decimal point (i.e. 0.123).

Thermal dilution cardiac output works by threading a catheter (a Swan-Ganz is what was used at the time) with a thermistor in its tip through the right side of a patient’s heart into their pulmonary artery. A small amount of iced saline is then injected through the catheter and the system times how long it takes for this cold pulse to go around the patient’s body and return. There are a number of uncertainties involved so it’s not a terribly accurate technique and the very best you could ever expect would be a precision of about 1/10th of a LPM and that’s being very generous.

We had no ability to actually determine if either meter was accurate and the best we could see was that both meters gave similar results on the same patient. Neither meter was particularly harder or easier to use than the other. Nevertheless the cardiac output meter with 3 digits after the decimal point won the evaluation hands down because everybody said it had to be more accurate. This may say something about human nature but it’s also just nonsense. Simply because somebody places extra digits after the decimal point doesn’t make the measurement more accurate.

I’ve seen many times where a test result is reported with more digits after the decimal point than you could reasonably expect to get from the equipment or the measurement. When new devices (software or smartphones for example) add new features that are of little value (other than probably as ad copy) it is called feature creep. When this happens with digits I think this should be called decimal creep.

When I review our PFT reports I see a number of results that are reported with too many digits. The one that bothers me the most is DLCO. I’ve written about a number of the problems we’ve encountered with DLCO measurements and in particular analyzer offset and gain. The manufacturer of our equipment claims the analyzer has an accuracy of 1%. Assuming that this means 1% of full scale (and not 1% at any reading) and plugging more or less normal values into the DLCO calculation, a single 1% error in either CO or the trace exhaled gas concentrations causes an error of approximately 0.8% in DLCO. A 1% error in both the CO and trace exhaled gas concentrations causes up to a 2.5% error in DLCO. A 1% error in both inhaled and exhaled gas concentrations can cause an error of up to 13% error in DLCO.

What this means is that even a single 1% error in any of the DLCO gas concentrations (let alone the inspired volume or the breath-holding time) will cause an error of approximately 0.3 ml/min/mmHg and therefore its accuracy can’t be any better than that. So why is DLCO reported out to two digits after the decimal point?

Similarly, our test systems report MIP and MEP with two digits after the decimal point. Our equipment manufacturer doesn’t provide any specifications for the pressure transducer but that doesn’t really matter. We calibrate our mouth pressures using a U-tube manometer that uses colored oil rather than water. The surface tension of the oil is less than water so in some ways its height is easier to read than water would be (due to a flatter meniscus) but even so, the scale lines are 0.2 cm H2O water pressure apart and you have to eyeball it carefully to get it to the pressure used to calibrate the transducer (10 cm H2O). I’ve calibrated transducers using U-tube manometers for years and don’t think that I can get it any closer than +/- 0.1 cm H2O. Unless you’re with the National Bureau of Standards I don’t see how it’s possible to calibrate a transducer with an accuracy of 0.01 cm H2O so again, why are results reported with two digits after the decimal point?

I will mention in passing that our lab’s database stores results as single-precision numbers which means that volumes and gas concentrations are stored out to at least five digits after the decimal point (i.e., 0.00001 L). This may be a reflection of the output from the test system’s A/D converters, but really, five digits?

There is at least one result however, that I think is reported with too few digits after the decimal point and that is the FEV1/FVC ratio. Our software reports both the observed and the predicted values as integers, i.e. with no digits after the decimal point. I realize that it is traditional to report the FEV1/FVC ratio as a percent, but to me it is a ratio and for this reason I’d like to see at least one digit after the decimal point. My concern is that I don’t know when the FEV1/FVC ratio is being rounded up or rounded down. Realistically this doesn’t matter for more than a small handful of patients but when you have somebody that is literally on the borderline between normal and abnormal it would help to make an informed decision.

One final peeve is that too often I see staff members both within and without the PFT Lab report decimal fractions without the leading zero (i.e., .78 rather than 0.78). Not only does this make it harder to read but it doesn’t meet the Joint Commission standards for clarity in reporting results. I can correct the lab’s technicians when I see them do this, but when it’s somebody outside the lab all I can do is let it pass.

This problem could be solved (at least to my satisfaction) if our reporting software allowed us to adjust the number of digits after the decimal point that appear on reports, but it doesn’t.  Decimal points are preset and cannot be altered.  We’re stuck with it at the moment and the best I can do is to add this to my list of gripes about our reporting software.

We need to get real about our decimal points and acknowledge that there are limits to the accuracy of our test measurements. Worrying about this may be a bit OCD-ish on my part but I think the number of digits after the decimal point clearly implies the level of accuracy of the result and too many digits after a decimal point gives a sense of accuracy and precision that just isn’t there. Let’s stop these creepy decimals!

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

I always like it when a patient does something during a test that makes me have to think about the basics of the test and what effect an error will have on the results. I was reviewing a report that had come across my desk and the technician performing the test had put “poor DLCO test reproducibility, fair quality in selected test” in the notes so of course I had to pull up the raw test data and take a look for myself.

The patient had performed three DLCO tests, two of which were completely unusable and one that was sort of okay but not really. Interestingly, the test system software thought it met the criteria for acceptability.

The ATS/ERS statement on DLCO testing says that the inspired volume needs to be at least 85% of the patient’s largest known vital capacity. Even though the patient’s inspired volume during most of the test was well below this threshold they made a further inspiratory effort just before exhaling and exceeded the threshold when they did. For this reason the software thought the effort was acceptable. This points out limitations in our testing system software, its hardware, and in the ATS/ERS statement as well.

When you read the ATS/ERS statement on DLCO testing it is clearly assumed that a patient will hold their breath at their maximum inspired volume throughout the test but I have been unable to find anything in the statement that actually says this. There is a great deal of discussion on the minimum parameters for the inspiratory maneuver, the breath-holding period and the expiration and we all “know” that the patient should do nothing but hold their breath until it comes time to exhale but this isn’t explicitly stated. This isn’t something that really needs to be spelled out for those of us who have spent any time performing DLCO tests but there are programmers and engineers who have no real familiarity with pulmonary function testing that rely on the ATS/ERS statements when they are designing software and hardware. If it isn’t in the statement, it doesn’t get put into the software (and sometimes even when it is in the statement it still doesn’t get put there).

Even so, everybody “knows” that a patient is supposed to reach their maximum lung volume at the beginning of the DLCO test and then hold it at that level during the remaining part of the test but it probably never occurred to anybody to test this assumption. I have to be honest and say I would have assumed that all patients did this or if they didn’t it was because they leaked air out instead. In this case it seems the programmers did not design the software to make sure that the maximum inspired volume was held throughout the breath-holding period but instead to only see if it occurred at any time during the breath-holding period, even if that was only for a fraction of a second.

Strictly speaking, the test system hardware should also help insure the patient holds their breath at the same volume through the test. Our test systems have a valve controlled by the technician that can be locked after a patient has inhaled at the beginning of the DLCO test. In our older volume-based test systems this locking valve prevents the patient from both inhaling and exhaling. Our newest systems however, use a demand valve to provide the DLCO gas mixture to the patient and the inlet for this is located on the patient side of the locking valve. A patient can’t exhale into the demand valve, so the locking valve still prevents the patient from exhaling, but it certainly doesn’t prevent them from inhaling from the demand valve.

This also presumes the technician actually closes the valve during the test and this isn’t always the case. Despite the fact that locking the valve only requires a single press of the [space bar] I’ve seen technicians who seem to think it is better (more fun?) to exhort the patient to hold their breath by themselves without any help. I think that patients need all the help they can get and that you are likely to get better test quality by closing the valve during test and this is the lab’s policy as well, but this doesn’t seem to stop some technicians from doing it the other way.

Normally I’d reject this DLCO test because it has a suboptimal inspired volume but this was the best the patient was able to perform so we needed to try to salvage it. So the question is what effect does this late, extra inspiratory effort have on the test results?

It was unlikely the patient’s lung was at its maximum surface area throughout most of the test. The most common error I see patients make with the DLCO test is to not exhale to RV before they inhale to TLC. This means their inspired volume is really equivalent to an inspiratory capacity not a vital capacity but it doesn’t necessarily mean they aren’t at TLC when they breath-hold. In this case however, when I used a ruler function on the graph I found that the average inspiratory volume was 21% less than the peak inspiratory volume. Even if you assume the peak inspiratory effort was at TLC, during most of the test the maximum lung volume was therefore below the 85% threshold and for this reason, the DLCO is probably underestimated.

On the other hand, the inspired volume is also used to calculate the alveolar volume (VA):

Where:

V_I = Inspired volume

Vd = Dead space volume

FI_trace = Inspired trace gas cocentration (helium or methane)

FA_trace = Exhaled trace gas concentration

In this case, the peak inspired volume occurred for only fraction of a second. This time period is probably too short to allow the DLCO gas mixture to re-distribute itself in any meaningful manner so the inspired volume is actually overestimated. This means that the VA is also overestimated. The DLCO calculation is largely a function of K, which is the rate of disappearance of carbon monoxide from the lung, and VA. Since K is a function of the inhaled and exhaled gas concentrations, this means that DLCO scales with VA, and that the patient’s DLCO was likely overestimated because the VA was overestimated.

The patient’s DLCO was probably underestimated because their lung’s surface was reduced through most of the test but at the same time it was probably overestimated because the alveolar volume was overestimated. Do these cancel each other out? In a real sense they can’t because trying to do this would be like adding apples and subtracting oranges but it does make it a touch more likely the results are not as inaccurate as would be expected. We ended up reporting the DLCO with the notation that it had suboptimal quality. It turns out the patient had a DLCO test with acceptable quality about a half a year ago and the present results were not significantly different but this too is not a reason by itself to report suboptimal results.

This was a suboptimal DLCO test and if there had been any alternative it would not have been reported. You often have to work with whatever a patient is capable of doing however and then it becomes important to have a good understanding of the tests so you can try to determine what effect their testing error has on the results. The most interesting thing about this test was that it pointed out a hole in the assumptions a lot of us have about breath-holding during the DLCO test.

References:

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

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

We’ve had some questions lately about some of our CPET guidelines. These questions were informational in nature not confrontational but they served to remind us that the reference values we use for CPET interpretation were developed and put in place at least ten years ago and it is past time they were reviewed. As a starting point I’ve been re-reading the ATS-ACCP and AHA statements on cardiopulmonary exercise testing. One sentence from the AHA statement concerning the Ve-VCO2 slope caught my eye. Specifically:

“… calculation of the Ve/VCO2 slope with all exercise data obtained from a progressive exercise test (initiation to peak effort) appears to provide additional clinical information compared with submaximal calculations (i.e. those that use linear data points before the steepening associated with ventilatory compensation for metabolic acidosis).”

Ve-VCO2 slope is calculated using a linear regression function and we have been calculating it using only the test data between the start of exercise and the anaerobic threshold. The AHA statement however says we should be calculating it using the data all the way up to peak exercise (the ATS/ACCP statement is mute on this point since it does not even discuss Ve-VCO2 slope other than as a graph). Because Ve-VCO2 slope is a key component in our assessment of CPET results it is important that we get this right.

Ve and VCO2 have a reasonably linear relationship up to the anaerobic threshold. After the anaerobic threshold ventilation is driven by acidosis as well as CO2. This means that the Ve-VCO2 slope tends to be steeper (greater change in Ve per unit of VCO2) after anaerobic threshold than it was before. A Ve-VCO2 slope calculated from the entire CPET will therefore have steeper slope than one calculated using just using rest to AT.

 

For decades the peak VO2 from an exercise test has been used to assess surgical risk and as a predictor of mortality and hospitalization. One particularly valid criticism in the use of peak VO2 is that it can be falsely reduced for reasons that have nothing to do with either cardiac or pulmonary status. Research has shown that the Ve-VCO2 slope is probably a better indicator than peak VO2 and since the Ve-VCO2 slope from rest to AT is linear this means that an accurate Ve-VCO2 slope can be obtained from even a submaximal exercise test. This is one of the reasons that I had thought the consensus was that Ve-VCO2 slope should be calculated only using data up until AT.

When I reviewed the literature referenced in the AHA statement I found several studies that indicate that although the start to AT (sub-maximal) Ve-VCO2 slope was a powerful predictor of an individual’s clinical outcome, the start to peak Ve-VCO2 slope was superior. The reasons for this are not completely clear but it was speculated that it is due to poorer cardiac function at higher levels of exercise which leads to greater acidosis and a steeper Ve-VCO2 slope after anaerobic threshold. At least one study indicated that the difference between the sub-maximal Ve-VCO2 slope and the Ve-VCO2 slope after AT was itself a significant predictor of outcome, and that the greater the difference, the poorer the outcome was.

It does seem to make sense therefore, to calculate Ve-VCO2 from start to peak exercise. One concern I have with this approach would be that the peak Ve-VCO2 slope, like peak VO2, is dependent on patient effort. For this reason it is somewhat unclear what its normal range is. The upper limit of normal for the sub-maximal Ve-VCO2 slope is considered to be 34. The peak Ve-VCO2 slope should always be greater than the sub-maximal Ve-VCO2 slope and for this reason it should probably not have the same upper limit of normal. The AHA statement is a bit vague on this point in that it says that a peak Ve-VCO2 slope less than 30 is normal and one greater than 40 is abnormal, leaving the actual upper limit of normal somewhat up in the air. This is something that needs further research since I have seen several studies using peak Ve-VCO2 slope that used an ULN of 34.

An additional concern is that the Ve-VCO2 slope is calculated using linear regression. This is certainly acceptable for a sub-maximal Ve-VCO2 slope but the Ve-VCO2 slope from an entire CPET is not linear. This leaves open to question exactly what the numerical value that is calculated for a peak Ve-VCO2 slope is really saying. It seems to me there are probably better ways to characterize the peak Ve-VCO2 slope other than linear regression but since I am not a statistician or mathematician I will have to wait for somebody else to address this issue.

For my lab it seems the best approach will be to continue to calculate the sub-maximal Ve-VCO2. Its upper limit of normal is reasonably well characterized and it is also well suited to assessing sub-maximal tests. In addition however, I will also start calculating the peak Ve-VCO2 slope and will use the AHA value of 40 as the upper limit of normal. This should also be a useful check on those times when the anaerobic threshold is indeterminate. I will be interested to see if there are any patients who have a normal sub-maximal Ve-VCO2 slope but an abnormal peak Ve-VCO2 slope, or if both slopes will always be abnormal. This is something I haven’t seen addressed in any studies.

Twenty-five years ago we only reported the Ve/VCO2 at AT but since then it has gotten more complicated. Now we report the Ve/VCO2 at AT, the lowest observed Ve/VCO2, the sub-maximal Ve-VCO2 slope and the peak Ve-VCO2 slope. I would like to pare these down but it’s difficult to determine which of these values, if any, should be dropped. There are proponents for each of these measurements but only a few studies that have compared each approach and these have been primarily limited to the ability to prognosticate survival or hospitalization rates and not particularly towards the causes of the differences. The relationship between Ve and VCO2 is multi-factorial and it is possible that each of these measurements is saying something slightly different about patient physiology. It’s also just as possible that they overlap each other and that a single measurement (peak Ve-VCO2 slope?) would be sufficient but at this moment the jury is still out.

References:

Arena R, Myers J, Aslam SS, Varughese EB, Peberdy MA. Technical considerations related to the minute ventilation/carbon dioxided output slope in patients with heart failure. Chest 2003; 124: 720-727.

ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Resp Crit Care 2003; 167: 211-277.

Balady GJ; et al. Clinician’s guide to cardiopulmonary exercise testing in adults: A scientific statement from the American Heart Association. Circulation 2010; 122: 191-225.

Chua TP, Ponikowski P, Harrington D, Anker SD, Webb-Peploe K, Clark AL, Poole-Wilson PA, Coats AJS. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronis heart failure. J Am Coll Cardiol 1997; 29: 1585-1590.

Corra U, Mezzani A, Bosimini E, Scapellato F, Imparato A, Giannuzzi P. Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity. Am Heart J 2002; 143: 418-426.

Ingle L, Goode K, Carroll S, Sloan R, Boyes C, Cleland JGF, Clark AL. Prognostic values of the Ve/VCO2 slope calculated from different time intervals in patients with suspected heart failure. Int J Cardiol 2007; 118: 350-355.

Koike A, Itoh H, Kato M, Sawada H, Aizawa T, Fu LT, Watanabe H. Prognostic powere of ventilatory responses during submaximal exercise in patients with chronic heart disease. Chest 2002; 121: 1581-1588.

Sun XG, Hansen JE, Garatachea N, Storer TW, Wasserman K. Ventilatory efficiency during exercise in healthy subjects. Am J Resp Crit Care Med 2002; 166: 1443-1448.

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

Recently I was trying to make some sense of an exercise test report that had come across my desk. Numerical results on our CPET reports are averaged over 30 second periods and there seemed to be a lot of variability from one time interval to the next. This isn’t uncommon in the first couple of minutes of an exercise test because patients often start off too hard and too fast, overshoot and then take a while to settle down into a steady pattern. This variability however, persisted throughout the entire test. I finally realized that what I was seeing was Exercise Oscillatory Ventilation (EOV).

It has been a while since I last saw a patient with EOV. Part of the reason for this is that EOV is a sign of relatively advanced heart failure and most of the patients who have cardiac disease have already had standard ECG stress testing and tend not to get referred for a cardiopulmonary exercise test (CPET). Having said that, it is a bit surprising that we don’t see this more often since there tends to be an association between pulmonary disease and cardiac disease and we do exercise tests relatively frequently on patients with combined lung and heart disease in order to determine their primary cause for shortness of breath. Nevertheless, even though one study estimated that up to 30% of patients with heart failure exhibit EOV (although most studies estimate it somewhere between 7% and 12%), it is not something we have ever seen with any frequency.

EOV is a condition where minute ventilation (Ve) rises and falls (oscillates), usually with a period between 30 to 60 seconds. EOV can persist throughout exercise or fall off at the higher exercise levels. Several researchers have indicated that it is often present at rest as well as during exercise but this not something I’ve seen in the few patients we’ve had with EOV. Interestingly, the oscillation in Ve comes primarily from a cyclic pattern in tidal volume.

EOV was first noticed only as a change in ventilation but it has since been realized that oxygen consumption (VO2) and CO2 production (VCO2), as well as PETO2 and PETCO2 rise and fall along with ventilation. At least one study has indicated there is reason to believe that pulmonary blood flow oscillates in these patients as well. Even though Ve, VO2 and VCO2 rise and fall together, the ventilatory equivalents, Ve/VCO2 and Ve/VO2, also tend to show an oscillatory pattern although this usually less pronounced than those of Ve, VO2 or VCO2. Because heart rate does not show this oscillatory pattern this means that O2 pulse oscillates as well.

One reason that EOV may not be recognized more frequently is that it tends to be obvious only when Ve (or VO2) is plotted against time. This graph is not considered part of the standard panel of exercise test graphs however, and this is because it usually isn’t particularly informative when assessing CPET results except perhaps as an overview. Our CPET system routinely plots Ve/VCO2 and Ve/VO2 versus time in order to help with the determination of the anaerobic threshold, but this is done on a breath by breath basis and is usually quite “noisy”. It’s difficult enough to determine the nadirs of Ve/VCO2 and Ve/VO2 let alone see any oscillation.

When properly graphed EOV is usually easy to recognize but like many other observations it lacks an official definition. One fairly concise definition used by researchers is a greater than 25% variation in the amplitude of minute ventilation persisting for more than 60% of the exercise period. Oscillation amplitude for this purpose is defined as:

EOV has only been observed in patients with heart failure and the cause of heart failure does not seem to be a factor. When matched with individuals with similar levels of heart failure, patients that exhibit EOV tend to have:

• higher left atrial volume
• higher right-sided heart pressures
• higher Ve-VCO2 slope
• lower peak Ve
• lower peak VO2
• lower PETCO2
• higher Vd/Vt
• an attenuated tidal volume response to exercise
• a higher mortality rate

Early research indicated that individuals with EOV tended to have a low left ventricular ejection fraction (i.e. less than 0.30). It’s not clear this is actually the case since more recent research has shown EOV occurring in some individuals with an ejection fraction greater than 0.40.

The causes of EOV remain unclear. Researchers have noted that in heart failure the components of the ventilatory control system are altered by information delay (prolonged circulation time), increased controller gain (overactive chemoreceptors) and a decrease in damping (impaired arterial baroreflex). A recent study hypothesized the elevated right-sided heart pressures promotes baseline hyperventilation with hypocapnia. When PaCO2 is driven below the apnea threshold the patient hypoventilates which in turn causes PaCO2 to rise and hyperventilation to resume. This may well be the case but this doesn’t explain why only some patients with elevated right-sided heart pressures develop EOV nor does it explain why the periodicity of oscillation remains relatively constant across a wide range of workload, cardiac output, ventilation and VO2.

From a practical viewpoint I’ve found that the presence of EOV makes it difficult to determine anaerobic threshold (AT) and the Ve-VCO2 slope. AT is usually calculated using the V-slope technique or by the nadir in Ve/VO2. I have always found the inflection point in the V-slope technique to be relatively subtle and for this reason have always felt that the Ve/VO2 nadir provided a clearer signal but since both Ve/VO2 and Ve/VCO2 oscillate along with Ve determining the nadir (i.e. which nadir?) becomes problematic. At least one researcher noted that using V-slope technique they were able to determine AT in only 34% of their patients with EOV compared to 72% of those without.

For a variety of reasons I calculate the Ve-VCO2 slope by entering results into a spreadsheet and using a linear regression function to calculate the actual slope and intercept. Below the anaerobic threshold Ve and VCO2 tend to have a very linear relationship. Plotting the Ve and VCO2 from the patient with EOV I found it to have much greater scatter than usual which makes it unclear whether the Ve-VCO2 slope calculated from linear regression was accurate or not. This is potentially important in this case because the patient was near the upper limit of normal and a slight increase in slope would have put them over the ULN.

Finally, because of oscillation, the VO2, VCO2 and Ve at peak exercise may or may not be the actual maximum. The ATS/ERS recommendations on exercise testing say that you should average the last 30 seconds of peak exercise data to obtain the maximum VO2 but this may be occurring at a nadir in the oscillation. When I review CPET test data I compare the maximum values to the 30 second averages and will replace the peak values in the report if it appears to be necessary but I always have concerns about doing this.

EOV is something that can be seen in an exercise test with a greater or lesser frequency depending on your patient population. It tends to be evident only when Ve, Vt, VO2 and VCO2 are plotted versus time. Although EOV may appear to be the result of a variable patient effort it is highly periodic and its rate tends to remain constant as long as it persists. It is associated with advanced heart failure and most researchers have indicated that the presence of EOV helps to pinpoint patients with an elevated level of risk and for this reason its presence should be included in the CPET report.

References:

Ben-Dov I, Sietsema KE, Casaburi R, Wasserman K. Evidence that circulatory oscillations accompany ventilatory oscillations during exercise in patients with heart failure. Am Rev Respir Dis 1992; 145: 776-771.

Corra U, Giordano A, Bosimini E, Mezzani A, Piepoli M, Coats AJS, Giannuzzi P. Oscillatory ventilation during exercise in patients with chronic heart failure. Clinical correlates and prognostic implications. Chest 2002; 121: 1572-1580.

Koike A, Shimizu N, Tajima A, Aizawa T, Fu LT, Watanabe H, Itoh H. Relation between oscillatory ventilation at rest before cardiopulmonary exercise testing and prognosis in patients with left ventricular dysfunction.

Leite JJ, Mansur AJ, de Freitas HFGm Chizola PR, Bocchi EA, Terra-Filho M, Neder JA, Lorenzi-Filho G. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol 2003; 41(12): 2175-2181.

Olson LJ, Arruda-Olson AM, Somers VK, Scott CG, Johnson BD. Exercise oscillatory ventilation: instability of breathing control associated with advanced heart failure. Chest 2008; 133: 474-481.

Yajima T, Koike A, Sugimoto K, Miyahara Y, Marumo F, Horoe M. Mechanisms of periodic breathing in patients with cardiovascular disease. Chest 1994; 106: 142-146.

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

The ATS/ERS recommendation for assessing the response to bronchodilator is based solely on changes in FEV1 or FVC. An FEV1 that does not improve significantly following bronchodilator inhalation is considered to be one of the hallmarks of COPD. Many individuals with COPD however, can have symptomatic relief and an improvement in their exercise capacity without a significant post-bronchodilator increase in FEV1. This means that FEV1 may not be the only criteria for assessing bronchodilator response.

One of the hallmarks of COPD is expiratory flow limitation. This can cause hyperinflation and is often reflected in an elevated FRC. It is also an important factor in exercise limitation. When ventilation increases during exercise in an individual with COPD, expiratory flow limitation causes the tidal volume and FRC to shift towards higher lung volumes. FRC is difficult to measure during exercise so this usually observed by measuring Inspiratory Capacity (IC).

COPD patients who don’t show a significant change in their FEV1 can respond to bronchodilators by becoming less expiratory flow-limited and when this happens their FRC decreases. Bronchodilator response in these individuals can therefore be assessed by measuring pre- and post-bronchodilator FRC or IC. At present there appears to be a consensus that an increase in IC or decrease in FRC of at least 0.30 liters or 12% should be considered to be a significant response.

At first glance it would seem that measuring FRC would be the most accurate way to assess post-BD improvement but there are a number of criticisms towards measuring FRC in patients with severe airway obstruction. Under some circumstances the FRC measured by plethysmography can be falsely elevated in individuals with COPD. It could also be argued that gas trapping can cause FRC to be underestimated when it is measured by helium dilution or nitrogen washout. For these reasons IC is probably a more reliable indication of a change in FRC which is also convenient because IC can be measured as part of an SVC maneuver more quickly than FRC and with simpler equipment.

This doesn’t mean that measuring IC doesn’t require a certain amount of care. IC is difference in volume between FRC and TLC. FRC is defined as the volume of the lung at the end of a normal exhalation and in any individual, not just those with COPD, FRC is a dynamic volume because it is balance point between a number of forces. For this reason determining where the “normal” end of exhalation resides is critical when measuring IC but is also somewhat poorly defined.

It should be relatively obvious that FRC cannot be determined when there is a leak.

It is also fairly obvious that FRC is difficult to determine when an individual is breathing erratically.

The ATS/ERS statement on spirometry states that for a SVC maneuver the subject be “… asked to breathe regularly for several breaths until the end-expiratory lung volume is stable (this usually requires at least three tidal manoeuvres)”. Other than this there is no specific definition for what determines a stable end-exhalation and like many other things that are “obvious” a stable exhalation is difficult to define.

Until we have a better definition of what constitutes a stable end-exhalation the best that we can do is to “eyeball” the results and try to choose results that appear to have good quality. This can be a problem because I’ve seen several spirometry systems, usually the simpler and less-expensive ones, where only numerical SVC results are displayed. When the SVC is shown graphically sometimes only the SVC component is displayed and sometimes the display is low resolution and small details cannot be seen. For all of these reasons an accurate end-exhalation level can only be determined when the tidal breathing component of the SVC test is displayed in its entirety and at a high enough resolution for small details to be evident.

Even when the tidal breathing component of the SVC is displayed correctly it is also necessary to be able to edit the end-exhalation level. I suspect that most spirometry systems do a reasonably good job of averaging the end-exhalation volume for the IC measurement, but that doesn’t mean they are always correct. Without the ability to edit SVC results there will be times where an adequate SVC maneuver will need to be discarded solely because of an error in the algorithm for determining end-exhalation.

Like other lung volumes, the highest IC is not necessarily the best or most accurate one and for this reason the IC maneuver should be performed several times and an average taken from the most repeatable results. The ATS/ERS statement on spirometry says that FVC and FEV1 are repeatable when results are within 0.15 L (0.10 L if the FVC is less than 1.0 liter) and it seems to be reasonable to expect the same level of repeatability from acceptable IC maneuvers.

Not all individuals with COPD will show post-bronchodilator improvements in IC or FRC. Research indicates that improvements tend only to be seen in individuals with expiratory flow limitation and hyperinflation. There is a general association between COPD severity and expiratory flow limitation but there are no simple methods for determining expiratory flow limitation and it is unclear how many patients with COPD who don’t show an improvement FEV1 will show one in IC or FRC. For these reasons I think that the best approach at present is for all patients with COPD to have their IC measured as part of their pre- and post-bronchodilator spirometry.

Measuring IC as well as regular spirometry will increase the amount of time spent testing a patient with COPD and it cannot be billed separately. Nevertheless, knowing whether or not a patient benefits from the use of a bronchodilator even if their FEV1 does not improve is valuable clinical information and should be considered to be a standard part of the care of an individual with COPD.

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.

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

Duranti R, Filippelli M, Bianchi R, Romagnoli I, Pellegrino R, Brusasco V, Scano G. Inspiratory capacity and decrease in lung hyperinflation with albuterol in COPD. Chest 2002; 122: 2009-2014.

O’Donnell DE. Assessment of bronchodilator efficacy. Is spirometry useful? Chest 2000; 117: 42S-47S.

O’Donnell DE, Forkert L, Webb KA. Evalution of bronchodilator response in “irreversible” emphysema. Eur Respir J 2001; 18: 914-920.

Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest 1998; 114: 1607-1612.

Taube C, Lehnigk B, Paasch K, Kirsten DK, Jorres RA, Magnussen H. Factor analysis of changes in dyspnea and lung function parameters after bronchodilation in chronic obstructive pulmonary disease. Amer J Respi Crit Care Med 2000; 162: 216-220.

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

The Maximum Voluntary Ventilation (MVV) test was initially described in 1933. It was the first pulmonary function test that involved inspiratory and expiratory air flow in a significant way and for this reason it helped to set the stage both conceptually and technically for the FEV1, the FEV1/FVC ratio and our present understanding of obstructive lung diseases. MVV is reduced in a variety of conditions, including obstructive, restrictive and neuromuscular diseases, but a reduced MVV is non-specific and this limits its clinical utility. Nevertheless, it continues to be performed both in clinical labs and for research, and for this reason it would seem to be a good idea to know how to assess MVV results.

As usual, there are two aspects to assessing pulmonary function results; test performance and normal values.

Currently the ATS/ERS statement on spirometry contains the only available standard for performing the MVV test. Unfortunately this standard also contains some significant flaws. Its primary recommendation is that the MVV test be performed with a tidal volume that is approximately 50% of the forced vital capacity and a breathing frequency of around 90 breaths per minute. These recommended values are problematic and some simple mathematics will show why.

A respiratory rate of 90 BPM means that there is 2/3 of a second for both inhalation and exhalation. With a 1:1 ratio for inspiration and expiration, there is only 1/3 of a second for exhalation. Since it normally takes a full second to exhale approximately 75% of the vital capacity (i.e. the FEV1), 1/3 of a second would only allow time to exhale 25% of the vital capacity (not exactly true of course, but it helps prove the point). How then is it possible to exhale 50% of the vital capacity, twice that amount, in the same amount of time? The answer is that it isn’t and if it was somehow possible for somebody to actually meet the ATS/ERS recommended values they would have an MVV that would be 45% to 100% higher than any of the predicted MVV’s. I suspect the ATS/ERS agrees this is a problem since following the initial recommendation it also says that “… since there are little data on MVV acceptability criteria, no specific breathing frequency or volume is required”.

The fact is that no single tidal volume recommendation is going to work for all patients and this is because the MVV tidal volume has to reside mostly within the maximal flow-volume loop envelope.

This means that increasing the MVV tidal volume comes at the expense of decreasing the average expiratory flow rate, which in turn will decrease the MVV.

In individuals with normal lungs, there is still a fairly broad range of lung volumes where the average expiratory flow rate is relatively high. When obstructive disease is present however, there is only a narrow range of lung volumes where high expiratory flow rates are possible and any attempt to increase tidal volume will dramatically decrease the average expiratory flow rate.

This means that a tidal volume anywhere near 50% of the vital capacity is probably going to be counterproductive in individuals with airway obstruction.

It’s not clear that a respiratory rate of 90 is correct either, since at least one study has indicated that MVV tends to decrease at respiratory rates above 80. In addition, since one of the primary clinical reasons to perform an MVV test is to assess an individual’s maximum ventilatory capacity for an exercise test and an exercise respiratory rate above 55 is considered abnormal. Having said that, MVV ventilation is not the same as exercise ventilation and they should not be considered equivalent.

I think that the final answer is that each individual is going to have their own optimum tidal volume and respiratory rate. The overall quality of an MVV should be judged first by multiplying an individual’s FEV1 x 40. The ATS/ERS standard says that an MVV less than 80% of this value is likely suboptimal. If a test result does not meet this criteria then subjects should be corrected if their respiratory rate is too high (greater than 90?) or too low (less than 60?), or if their tidal volume is too large (greater than 50% of VC?) or too small (less than 25% of VC?).

Compared to most other spirometric parameters there are relatively few reference equations for MVV. This number is even more limited by the need to exclude MVV population studies prior to the 1960’s. Relatively early in the study of MVV there was some appreciation of equipment resistance and inertia but it was not until the 1960’s that testing systems able to routinely produce accurate MVV results came into common use.

As usual there are always problems associated with selecting a specific reference equation. Several of the reference equations, particularly those for females, are quite limited because only a single factor, either age or height, is used to calculate the predicted MVV and for this reason these reference equations should be avoided. Most of the studies have a limited population size with a limited range of ethnicities. This makes it unclear what effect, if any, ethnicity has on predicted MVV.

More than one study however, has shown there is a strong relationship between FEV1 and MVV. Depending on the study FEV1 can be multiplied by 35, 37.5 or 40 to obtain the predicted MVV. Since FEV1 is an expiratory measurement, any limitations to inspiratory flow will affect MVV as well, but inspiratory airway obstruction is relatively rare. Because the reference equations for FEV1 are well characterized by age, sex and ethnicity I think it is probably best to use FEV1 to derive the predicted MVV, particularly given the limitations of the existing MVV population studies. Since the ATS/ERS uses FEV1 x 40 to judge the adequacy of the MVV test then it would also seem best to use predicted FEV1 x 40 to derive predicted MVV as well.

I still have significant reservations about the utility of the MVV test. Because it is reduced in many different lung diseases it has little specificity and for this reason its clinical utility is limited. In addition I think that it is a stressful test for patients with poor lung function but even individuals with normal lung function can have difficulty performing the test correctly. The most common uses of the MVV test are as a pre-exercise assessment and as a general indication of lung health. For these reasons the MVV test continues to be performed so those performing it need to have a reasonable idea how it should be assessed.

Male MVV Reference Equations

Study:	No:	Age Range:	Equation:
[A]	247 M+F	21-75	(3.65 x ht(in)) – (0.814 x age) – 76.78
[B]	62	20-65	180.5 – (0.1288 x age)
[C]	879	15-79	(3.02915 x ht(in)) – (0.81621 x age) – 37.94893
[D]	270	20-70	(3.943 x ht (in)) – (0.7629 x age) – 102.5
[E]	468	20-65	(3.404 x ht(in)) – (1.26 x age) – 21.4
[F]	50	20-80	199.1 – (1.12 x age)
[G]	130	17-78	(4.2776 x ht(in)) – 159.01
[X]			NHANESIII FEV1 x 40

Female MVV Reference Equations:

Study:	No:	Age Range:
[A]	247 M+F	21-75	127.43 – (0.629 x age)
[B]	58	20-65	113.1 – (0.618 x age)
[C]	452	15-79	(2.13844 x ht(in)) – (0.68503 x age) – 4.86957
[E]	50	20-80	147.4 – (0.76 x age)
[G]	153	16-68	(2.106 x ht(in)) – 51.7555
[X]			NHANESIII FEV1 x 40

References:

Bartlett RG, Phillips NE, Wolski G. Maximum voluntary ventilation prediction from the velocity-volume loop. Chest 1963; 43: 382-392.

[A] Bass H. The flow volume loop: Normal standards and abnormalities in chronic obstructive pulmonary disease. Chest 1973; 63: 171

[B] Birath G, Kjellmer I, Sandqvist L. Spirometric studies in normal subjects. Part II. Ventilatory capacity in adults. Acta Med Scand 1963; 173: 193.

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.

Campbell SC. A comparison of the maximum voluntary ventilation with the forced expiratory volume in one second: an assessment of subject cooperation. J Occup Med 1982; 24: 531-533.

[C] Cherniak RM, Raber MB. Normal standards for ventilatgoryfunction using an automated wedge spirometer. Am Rev Resp Dis 1972; 106: 38

Dillard TA, Hnatiuk OW, McCumber TR. Maximum voluntary ventilation. Spirometric determinants in chronic obstructive pulmonary disease patients and normal subjects. Amer Rev Resp Dis 1993; 147: 870-874.

[X] 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

Harber P, SooHoo K, Tashkin DP. Is the MVV:FEV1 ratio useful for assessing spiromtry validity? Chest 1985; 88: 52-57.

[D] Hedenstrom H, Malmberg P, Fridrikkson HV. Reference values for lung function tests in men: regression equations with smoking variable. Upsala J Med Sci 1986; 91: 299-310

[E] Kory RC, Callahan R, Boren HG, Syner JC. The Veterans Administration-Army cooperative study of pulmonary function. Part I. Clinical spirometry in normal men. Am J Med 1961; 30: 243

[F] Neder JA, Andreoni S, Lerario MC, Nery LE. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Research 1999; 32: 719-727

[G] Roa CC, et al. Normal standards for ventilatory function tests in adult Filipinos. Phillipine J Int Med 2013; 51(1): 1-6.

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

One of the key reasons to perform spirometry is to measure expiratory flow rates. The flow rate of air through any system is primarily a function of driving pressure and resistance. Since there are limits to anybody’s ability to increase driving pressure (and physiological reasons why airflow does not continue to increase when driving pressure exceeds a certain threshold value) FEV1 is largely related to the amount of resistance in the airways.

The gold standard for measuring airway resistance (Raw) has been plethysmography. Like many other pulmonary function tests measuring Raw depends on a series of assumptions and a standardized approach to assessing the results. One of the standardizations is that a Raw maneuver must always be paired with a TGV maneuver. Although the knowledge of lung volume allows values like specific resistance (sRaw) and specific conductance (sGaw) to be calculated, this is not the reason for the TGV maneuver at all.

Resistance is calculated from:

 

Inspiratory and expiratory flow rates are relatively easy to measure but the driving pressure, which in this case is alveolar pressure, is not. For this reason an indirect approach is needed to estimate alveolar pressure.

The measurement of lung volumes in a plethysmograph is made when a subject attempts to breathe against a closed mouthpiece. Pressure inside the mouthpiece (which is assumed to be alveolar pressure) is plotted against the pressure inside the box.

The slope of the line, which is

combined with knowledge of the volume of air inside the box and the scaling factors of the pressure signals allows thoracic gas volume (TGV, the volume in the lungs at the time the mouthpiece was closed) to be calculated. More importantly it also shows the relationship between alveolar pressure and box pressure.

The Raw test maneuver consists of having the subject pant through a flow sensor in a closed plethysmograph. Flow rate is plotted against box pressure.

Breathing requires a pressure gradient between the mouth and the alveoli. During inhalation pressure in the aveoli has to be less than the ambient atmospheric pressure and during exhalation is has to be greater. This means that when a subject breathes inside a closed plethysmograph because the volume of air inside the box does not change, box pressure will increase during inhalation and decrease during exhalation. Since the relationship between box pressure and alveolar pressure can be found from the TGV maneuver this means that alveolar pressure can be derived from box pressure.

The assumption that Palv is directly proportional to Pbox is not perfectly correct however. The airways are open to atmosphere during the Raw panting maneuver and closed off during the TGV maneuver. To correct for this it is usually assumed that the entire deadspace between the alveoli and mouthpiece (which includes the airways, mouth and apparatus deadspace) is on average at half the pressure of the alveoli. There is a somewhat complex formula that takes this into consideration but it is really the ratio between TGV and one-half the deadspace that matters and for most people this would indicate that Palv is probably underestimated by around 5%.

I have equivocal feelings about the clinical utility of Raw. About 20 years ago I was involved in performing Raw for a research study. The research subjects were highly motivated but we had to settle for a baseline repeatability of +/- 40% in Raw and SGaw even after multiple practice sessions and this made it hard to find any statistical significance in the study’s results (although strictly speaking there may not have been any significance but the researchers were convinced there was). This variability indicates that changes in Raw have to be large to be notable which is also reflected in the fact that the normal range for Raw is relatively large.

The contour of Raw loops can be diagnostic since different airway diseases can alter the loop in distinct ways. Recognition of flow-volume loop contours is aided by the fact that there is a standard convention for displaying flow and volume. This is not the case for Raw loops since I’ve found that which axis flow and box pressure are placed on as well as which direction is positive and which is negative can vary from one research article to another.

A final point is that the airway resistance during inspiration can be different from that during expiration particularly in lung diseases like emphysema. My lab’s test software does not allow us to make this differentiation and in fact averages the Raw slope from both inspiration and expiration.

The advantage of Raw measurements is that they can be performed near FRC. There are many researchers that believe that the deep inspiration that accompanies an FVC maneuver alters bronchial tone and affects the ability to recognize bronchoconstriction. In addition, it is possible for Raw maneuvers to be performed by individuals that are unable for any number of reasons to perform spirometry adequately.

Raw varies with lung volume in a curvilinear fashion and is lower at high lung volumes and higher at low lung volumes. Conductance (Gaw) which is the inverse of Raw (1/Raw) also varies with lung volume, but linearly. Specific conductance (SGaw) which is Gaw/TGV is reasonably linear across all lung volumes and it is for this reason that SGaw is probably the most useful and commonly reported value from Raw measurements. This is in itself a reason to perform a TGV maneuver along with a Raw maneuver, but without the TGV maneuver it wouldn’t be possible to measure Raw in the first place.

References:

Blonshine S, Goldman MD. Optimizing performance of respiratory airflow resistance measurements. Chest 2008; 134: 1304-1309.

Dubois AB, Botelho SY, Comroe JH. A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. J Clin Invest 1956; 35: 327-335.

Goldman MD, Smith HJ, Ulmer WT. Whole-body plethysmography. Eur Respir Mon 2005; 31: 15-43.

Hemingway A. Measurement of airway resistance with the body plethysmograph. Charles C. Thomas publisher, copyright 1973.

Kaminsky DA. What does airway resistance tell us about lung function? Respir Care 2012; 57(1): 85-96.

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