Author: Richard Johnston

In patients with lung disease the use of supplemental oxygen during exercise increases oxygen consumption, endurance time and maximum workload, and decreases the sensation of dyspnea without increasing minute ventilation and maximum heart rate. My lab is occasionally asked to perform a CPET with an elevated FIO2 (hyperoxic CPET). We are capable of doing this but I’ve always had reservations, partly about the logistics involved in performing the CPET but more importantly with the interpretation of the results.

First, although it is certainly possible to perform some kinds of exercise test while the patient gets oxygen via a nasal cannula or mask, adding oxygen during a CPET requires that the patient breathes a hyperoxic gas mixture through their mouthpiece. Most commonly this is done by adding a two-way valve to the test system that is in turn attached to a reservoir bag which is filled from an oxygen blender.

Although functional, this adds extra dead-space and the valves add extra resistance, both of which increases the patient’s work of breathing. From a practical standpoint it also adds a fair amount of extra weight to the breathing manifold, often more than is comfortable for the patient. This means that some method for supporting the manifold must also put in place. About 25 years ago I performed CPETs using a treadmill that had a support arm and at that time the approach recommended by the equipment manufacturer was to suspend the breathing manifold using rubber tubing. This worked in that it supported the weight of the breathing manifold, but it didn’t do anything about its mass or inertia and when a patient transitioned from a walk to a jog, the mouthpiece manifold would bang against the patient’s teeth and mouth.

About 15 years ago my lab was moved from one location to another within the hospital and we weren’t able to bring the treadmill with the support arm with us. For this reason we started having one of our technicians stand next to the treadmill and help support the additional weight and found that this actually worked rather well. When we transitioned to a bicycle ergometer we continued to do this. This meant that we needed an additional technician to perform the CPET but they are only needed during the actual CPET.

Since the patient is breathing from a reservoir bag, it is important that this remains filled with a sufficient amount of gas. Although most patients that have a CPET with supplemental oxygen have lung disease, that doesn’t mean that they aren’t able to reach a relatively high minute volume. This in turn means that both the oxygen blender and the flowmeter must be able to provide sufficiently high gas flow rates during the test. It also means that care must be taken during the test to adjust the flow rate in order to keep the reservoir bag filled. If it isn’t you will limit the patient’s tidal volume and the test will end earlier than it should (which I know all too well from experience). We usually have the technician that is supporting the patient’s mouthpiece keep an eye on the reservoir bag volume and adjust the flow rate.

The logistics of providing a hyperoxic gas mixture will raise the complexity of a CPET, but not unmanageably so. A far bigger problem is interpreting the results although to some extent this depends on the reason the CPET was being performed in the first place.

Numerous studies have shown that patients with COPD and ILD will improve their maximum VO2 when given supplemental oxygen and that this occurs without increasing their minute ventilation or heart rate. This also acts to skew other gas exchange values. About 15 years ago I was reviewing an exercise test performed with an FIO2 of 35% on a patient with moderate-severe COPD. I noticed that the patient’s Ve/VCO2 at anaerobic threshold was normal (<35), the SpO2 was above 95% throughout the test and that the maximum PETCO2 was above 40. These factors would usually indicate that the patient had no pulmonary vascular disease, but the patient had performed a DLCO test about a week previously and it was around 40% of predicted.

My best guess as to what was happening was that by lowering the minute ventilation needed for a certain level of VO2, that also means that it was lowered for VCO2 as well, which in turn means that the Ve/VCO2 was lowered. Normally PETCO2 on patients with COPD is reduced because of an increased Vd/Vt, but in this case I suspect that the patient was hypoventilating relative to his VCO2 which in turn would cause PETCO2 to rise. The elevated PETCO2 could also be because the patient was able to reach a relatively high level of exercise and when this occurs PETCO2 can be affected by the increased PvCO2 returning to the lung. Some studies have showed that PaCO2 increases with an elevated FIO2 so the first reason may be more correct.

Since that time I’ve paid careful attention to the results from hyperoxic CPETs but haven’t seen as distinct a shift in gas exchange values. Although I suspect this occurs to one degree or another when an elevated FIO2 is used the magnitude of the effect is difficult to assess on a case by case basis. Changes in Ve/VCO2 have not been studied to any extent so it is unclear to what degree it changes, if it changes at all. Interestingly research has showed that VCO2 tends to decrease when an elevated FIO2 is used and this appears to be related to a reduced lactate.

The last several times we’ve performed CPETs with supplemental oxygen they were for the pre-op assessment of oxygen-dependent patients, and I think this is particularly problematic. One of the most critical results obtained from a CPET is the maximum oxygen consumption and this is used as part of an algorithm for determining the safety of a surgical procedure. A max VO2 above 15 ml/kg/min is generally taken as an indication that thoracic surgery is reasonably safe. This threshold comes from studies performed on room air however, and it is unlikely that a max VO2 greater than 15 ml/kg/min that was obtained with an elevated FIO2 has the same meaning.

In general, the maximum VO2, exercise time and workload increases when an elevated FIO2 is used during exercise. At the same time the maximum minute ventilation and maximum heart rate do not change. The VO2 at anaerobic threshold also tends to increase. There is some correlation between the FIO2 used during exercise and the degree to which VO2 improves but the degree of improvement is not predictable within a single individual. The problem that comes with interpreting a hyperoxic CPET is that the reference and threshold values are based on room air testing. Values that would be abnormal when a CPET was performed with room air are often within normal limits when a hyperoxic gas mixture is used. Unless there are very specific goals in performing a CPET with an elevated FIO2 interpretation of results is very difficult.

Given this fact it is unclear to me what clinical value a CPET with supplemental O2 really has. Having said that, since patients are able to exercise longer and reach a higher workload this gives an opportunity for cardiovascular limitations to arise that would otherwise wouldn’t be detected. An additional exception is when a CPET is performed prior to starting pulmonary rehabilitation when the rehabilitation is going to be performed with supplemental O2 since any limitations detected during the CPET are relevant to rehabilitation.

CPETs can be performed with an elevated FIO2. The methods for doing this are relatively straightforward but the interpretation of the results is made difficult by the fact that values that are routinely monitored during a CPET are significantly skewed by the use of an elevated FIO2 and the amount of skewing is not predictable. For this reason there are no clear guidelines for interpreting a hyperoxic CPET and that the reasons for performing such a test need to be clear before it is attempted.

References:

Astorino TA, Robergs RA. Effect of hyeroxia on maximal oxygen uptake, blood acid-base balance, and limitations to exercise tolerance. JEPOnline 2003; 6: 8-20.

Harris-Eze AO, Sridhar G, Clemens RE, Gallagher CG, Marciniuk DD. Oxygen improves maximal exercise performance in interstitial lung disease. Am J Respir Crit Care Med, 1994; 150: 1612-1622.

Marcus CL, Bader D, Stabile MW, Wang CI, Osher AB, Keens TTG. Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease. Chest 1992; 101: 52-57.

Somfay A, Porszasz J, Lee SM, Casaburi R. Dose-response effect of oxygen on hyperinflation and exercuse

Stein DA, Bradley BL, Miller WC. Mechanisms of oxygen effects on exercise in patients with chronic obstructive pulmonary disease. Chest 1982; 81(1): 6-10.

Stellingwerff T, LeBlanc PJ, Hollidge MG, Heigenhauser GJF, Spriet LL. Hyperoxia decreases muscle glycogenolysis, lactate production and lactate efflux during steady-state exercise. Am J Physiol Endocrinol Metab 2006; 290: E1180-E1190.

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

Although we routinely use mouthpieces, noseclips and occasionally masks for our testing, all of these alter respiration in one way or another. Opto-electronic plethysmography (OEP) is a completely non-invasive technique for measuring chest wall volume that also allows for regional differences in expansion and contraction of the thorax to be detected.

The basic idea is simple and is the same as is used in cinematic motion-capture systems. Small (6-10 mm) reflective hemispheres are attached to a subject’s torso with double sided tape. A set of 4, 6 or 8 high-speed (60-120 frames/sec) CCD cameras are then used to monitor both the overall and the relative motion of the hemispheres while the subject breathes. The accuracy of these measurements is claimed to be on the order of 0.2 mm.

The volume enclosed by the markers is analyzed geometrically by using a triangular or polyhedronal mesh. Since the triangles or polyhedrons are flat and human thoraxes are round-ish, volume tends to be underestimated to some degree. The amount of underestimation is closely related to the number of markers that are used and where they are placed. Research has shown that around 50 markers are needed for supine patients when only the anterior thorax is measured and more than 80 are needed for full coverage of upright patients. Reflectors need to cover the entire thorax, usually from the jugular notch on the upper chest to the iliac crest near the hips.

OEP has an accuracy that is similar to the ATS/ERS standards for spirometry. One study estimated that the coefficient of variance for static thoracic volume measurements was 2% and 3.5% for changes in thoracic volume. Another study showed a similarly small discrepancy of -2.4 +/- 3.9% when OEP was compared to volumes measured by a flow sensor during both light and heavy exercise.

OEP isn’t going to replace spirometry anytime soon however, since placing the reflectors takes up to 45 minutes. Calibration of the cameras and reflectors can take additional time as well. At least one study indicated that placement of the reflectors has to be exceptionally precise and that errors of more than 1 mm in placement made the reflector unrecognizable to the computer and required manual adjustment in the software. Subjects being measured must also be bare chested throughout the process which is something that some patients may not be comfortable with.

In addition, OEP can only measure the volume and change in volume of the external thorax, not the volume of the lung and not the actual expiratory (or inspiratory) flow at the mouth. Air inside the thorax must be compressed (or rarified) for gas flow to occur. The actual flow rate of expired (or inspired) gas will therefore be dependent on the pressure gradient between the atmosphere and the lungs, and the resistance of the airways. Although several studies have shown good correlation between tidal volumes measured by OEP and spirometers, a comparison of expiratory and inspiratory flow rates does not appear to have been made.

The greatest advantage that OEP has over conventional spirometry is that it permits separate measurement of up to six components of the thorax. These are the right and left sides of the pulmonary rib cages, abdominal rib cages and abdomen. Differences in these compartments during different breathing maneuvers are particularly useful in assessing assymetrical breathing patterns.

For example, a definitive diagnosis of unilateral diaphragmatic paralysis usually requires fluoroscopy, ultrasonography or phrenic nerve stimulation with diaphragmatic electromyography all of which tend to require experienced specialists and/or specialized equipment. One study has shown that when unilateral diaphragmatic paralysis is present the change in thoracic volume on the affected side during tidal breathing and inspiratory capacity maneuvers is significantly less than it is on the unaffected side. This raises the possibility that OEP could diagnose this kind of paralysis more quickly and easily than it is at present.

OEP has been used to research chest wall motion during speech; expiratory flow limitation during exercise; ventilation during hypercapnia; asymmetrical breathing from hemiplagia; hyperinflation in asthmatics during histamine-induced bronchoconstriction; thoracic motion during cough, laughter and unsupported upper arm exercise; the decrease abdominal (diaphragmatic) motion from muscular dystrophy; respiratory effort while walking; the contribution of abominal volume to dynamic hyperinflation in COPD; the contribution of abdominal volume to supine tidal volume in muscular dystrophy and diaphragmatic motion during supine breathing.

Clinically, OEP has been used to assess the respiration of newborns and ventilator patients, and has also been used to assess hyperinflation in patients with COPD during exercise. At the present time however, there is no CPT4 code for OEP and Medicare will not pay for it. In addition, OEP is a time-consuming and cumbersome process in the hospital setting and its primary value continues to be in research.

A newer technique that is similar to OEP is Structured Light Plethysmography (SLP). A grid is projected onto a patient’s chest, and like OEP the three-dimensional motion of the grid during breathing is detected by a set of cameras.

Despite the fact that a SLP system is commercially available it is unclear what level of accuracy SLP has versus OEP and versus conventional spirometry. On-line demonstrations of SLP have shown a projected grid that only covers the central part of the anterior chest. This may be acceptable for a supine breathing assessment but OEP researchers have emphasized the need measure motion at the margins of the thorax even for supine measurements. A number of meeting abstracts concerning SLP have been published but I have been unable to find any journal articles on the subject.

OEP is an interesting technique that at present is more suited for research than it is for a clinical PFT Lab. Having said that, a primary limitation of OEP is the ability to detect motion via reflectors that must be affixed to a subject’s thorax. Improvements in processing power and machine vision may make it possible to assess thoracic volume without the need to place reflectors. Since OEP (and SLP) can only measure changes in volume these techniques cannot replace traditional lung volume and diffusing capacity measurements. There are also reasons why OEP may have a limited ability to measure inspiratory and expiratory flow rates and this may well mean that it will be unable to replace spirometry as well.

The ability to detect asymmetrical breathing patterns however, is a relatively unique ability of OEP. It may well turn out that when measuring thoracic compartmental motion is easy to measure asymmetrical breathing may be found to be a more common problem than currently believed.

Product links:

OEP: BTS Bioengineering

SLP: Pneumacare

References:

Aliverti A, Stevenson N, Dellaca RL, Lo Mauro A, Pedotti A, Calverley PM A. Regional chest wall volumes during exercise in chronic obstructive pulmonary disease. Thorax 2004; 59: 210-216.

Aliverti A, Dellaca R, Pelosi P, Chiumello D, Pedotti A, Gattinoni L. Optoelectronic plethysmography in intensive care patients. Amer J Respir Crit Care Med 2000; 161: 1546-1552.

Boudarham J, Pradon D, Prigent H, Falaize L, Durand MC, Meric H, Petitjean M, Lofaso F. Optoelectronic plethysmography as an alternative method for the diagnosis of unilateral diaphragmatic weakness. Chest 2013; 144(3): 887-895.

Cala SJ, Kenyon CM, Ferrigno G, Carnevali P, Aliverti A, Pedotti A, MacKlem PT, Rochester DF. Chest wall motion and lung volume estimation by optical reflectance motion analysis. J Appl Physiol 1996; 81: 2680-2689.

de Boer WH, Lasenby J, Cameron J, Wareham R, Ahmad S, Roach C, Hills W, Iles R. SLP: A zero-contact non-invasive method for pulmonary function testing. Paper presented at the 2010 British Machine Vision Conference.

de Faria NS, et al. Opto-electronic plethysmography: noninvasive and accurate measurement of the volume of the chest wall and its different thoraco-abdominal compartments. Med Sci Tech 2013; 54: 147-150.

Dellaca R, Ventura ML, Zannin E, Natile M, Pedotti A, Tagliabue P. Measurement of total and compartmental lung volume changes in newborns with optoelectronic plethysmography. Pediatric Research 2010; 67(1): 11-16.

Ferrigno G, Carnevali P, Aliverti A, Molteni F, Beulcke G, Pedotti A. Three-dimensional optical analysis of chest wall motion. J Appl Physiol 1994; 77(3): 1224-1231.

Lanini B, Blanchi R, Romagnoli I, Coli C, Binazzi B, Gigliotti F, Pizzi A, Grippo A, Scano G. Chest wall kinetics in patients with hemiplagia. Amer J Respir Crit Care Med 2003; 168: 109-113.

Layton AM, Garber CE, Basner RC, Bartels, MN. An assessment of pulmonary function and ventilation kinematics by optoelectronic plethysmography. Clin Physiol Func Imaging 2011; 31: 333-336.

Layton AM, Moran SL, Garber CE, Armstrong HF, Basner RC, Thomashow BT, Bartels MN. Optoelectronic plethysmography compared to spirometry during maximal exercise. Respir Physiol & Neurobiology 2013; 185: 362-368.

Lo Mauro A, D’Angelo MG, Romei M, Motta F, Colombi D, Comi GP, Pedotti A, Marchi E, Turconi AC, Bresolin N, Aliverti A. Abdominal contribution to tidal volume as an early indicator of respiratory impairment in Duchenne muscular dystrophy. Eur Respir J 2010; 35: 1118-1125.

Parreira VF, Vieira DSR, Myrrha MAC, Oessoa IMBS, Kage SM, Britto RR. Optoelectronic plethysmography: a review of the literature. Braz J Phys Ther 2012; 16: 439-453.

Romagnoli I, Lanini B, Binazzi B, Bianchi R, Coli C, Stenardi L, Gigliotti F, Scano G. Optoelectronic plethysmography has improved our knowledge of respiratory physiology and pathophysiology. Sensors 2008; 8: 7951-7972.

Viera DSR, Hoffman M, Pereira DAG, Britto RR, Parreira VF. Optoelectronic plethysmography: intra-rate and inter-rater reliability in healthy subjects. Respir Physiol & Neurobiology 2013; 189: 473-476.

Vogiatzis I, Georgiadou O, Golemeti S, Aliverti A, Kosmas E, Kastanakis E, Geladas N, Koutsoukou A, Nanas S, Zakynthinos S, Roussous Ch. Patterns of dynamic hyperinflation during exercise and recovery in patient with severe chronic obstructive pulmonary disease. Thorax 2005; 60: 723-729.

Wang HK, Lu TW, Liing RJ, Shih TF, Chen SC, Lin KH. Relationship between chest wall motion and diaphragmatic excursion in health adults in supine position. J Formos Med Assoc 2009; 108)(7): 577-586.

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

Since I started performing exercise tests I’ve used both treadmills and bicycle ergometers. There are a several reasons that make ergometers somewhat better for exercise testing than treadmills. Most importantly the reduced noise and physical motion makes it easier to get blood pressure measurements and better quality ECG’s. In addition the workload can be set fairly precisely and they are safer for patients. Treadmills do have some advantages however, since patients are usually able to achieve a higher maximum oxygen consumption (~10%) and for many individuals walking is more natural than riding a bicycle.

When I’ve used a treadmill for exercise testing I’ve always used one version or another of the Bruce protocol. This choice was made by my medical directors but it has always seemed to get patients to their maximum exercise capacity within a reasonable period of time and it seemed to provide reasonable workloads for patients over a broad range of physical abilities. About a dozen years ago (the last time my PFT lab was moved) we no longer had room for a treadmill and replaced it with an ergometer. Since then, I haven’t thought much about treadmills and treadmill protocols.

Recently I was talking with a physician who is going to be performing exercise research with a treadmill. When he showed me the treadmill protocol he was planning on using I thought that the initial speed (3.3 MPH) was too high. Since his study population is going to consist of obese, deconditioned asthmatics, I suggested that for patient safety that it would be better to start at a lower speed and elevation. He asked if I could suggest a different treadmill protocol but I had to reply that all I had ever used was the Bruce protocol.

This brought up an interesting question however, and that is whether there is any such thing as an optimal treadmill protocol. To answer this question I undertook a broad survey of treadmill protocols and have to say that the answer is probably no. Strictly speaking, each treadmill protocol is intended for a specific range of physical effort and the selection of any one protocol has to be based on the expectations and limitations of a patient’s physical abilities.

There are several ways to categorize the different treadmill protocols, but I think that the most relevant may be in their workload. Treadmill workloads are usually expressed in METS. A MET (Metabolic Equivalent of Task) is an oxygen consumption of 3.5 ml/kg/min. The METS that are expected from a given speed and elevation of a treadmill are based on averages and for this reason cannot be used to predict an individual’s actual oxygen consumption.

[Note: Several years ago I got an exercise test report from the hospital’s cardiology lab which included the patient’s maximum oxygen consumption. Since as far as I knew the lab didn’t have a metabolic cart I wondered where the numbers came from. In particular I wondered if they had acquired a metabolic cart and if so why VCO2 and Ve weren’t reported. It turned out the lab had acquired some new stress ECG equipment and the default report included a conversion from the predicted METs of the patient’s treadmill speed and elevation into VO2. They removed this from the report shortly after I asked about it although whether this was due to my question is debatable.]

In particular METS scale poorly with body weight. Nevertheless, METS are a way of gauging the relative workload of different protocols. When looked at in terms of their maximum METS, is is apparent that specific protocols are intended for either debilitated, normal or athletic individuals.

One way to select a treadmill protocol for an individual is therefore by comparing a protocol’s range of METs versus the patient’s expected maximum oxygen consumption. Because METs scale poorly with weight however, the patient’s maximum VO2 in ml/kg/min should probably be obtained from their maximum predicted VO2 in ml/min divided by their predicted body weight rather than their actual body weight. An individual’s maximum expected VO2 needs to be adjusted downwards, of course, if the patient is debilitated and upwards if they are fit and athletic.

Another factor though, is the expected length of the test. There are a variety of reasons to perform exercise tests but my primary reason is to obtain an individual’s maximum oxygen consumption. If an exercise test’s workload increases too fast, the patient’s VO2 may underestimated due to the time constants between oxygen consumption at the cellular level and how it is measured at the mouth. Too steep a workload may also cause an individual to stop the test earlier than necessary simply because the test is “too hard”. On the other hand, if the test’s workload increases too slowly, an individual may stop the test before reaching their maximum VO2 simply because they are exhausted from the length of the test. For maximum VO2 five minutes is likely too short a time period and 15 minutes is probably too long. The optimum length of a test is therefore around 10 minutes and so it is the expected METs at 10 minutes that should be evaluated for a treadmill protocol and not the protocol’s maximum METs.

A final factor when selecting a treadmill protocol has to be patient safety. When an individual has limitations asking them to walk (or run) too fast or to climb too steep of a grade is contraindicated.

The most commonly used treadmill protocols have fixed changes in speed and elevation. The individual stages are usually specified with a certain time length, but this factor is often modified and the same protocol can have different time lengths. Other than the length of time it takes to get to an individual’s maximum oxygen consumption, I am not sure the length of the stages matters all that much (although if it is too long the test becomes more like a steady state rather than an incremental test). There is a convenience factor in associating changes in speed and/or elevation with blood pressure measurements, but there is no particular reason this has to be the case.

There are a number of treadmill protocols whose speed and/or elevation are not fixed in advance. Several of these allow the patient to set the walking (or running) speed and then just increase the treadmill elevation. There are also a couple that use branching logic and the speed and elevation vary according to values measured during the test. I think that these type of protocols are better suited to a sports medicine setting but there is no reason they can’t be used in a clinical lab.

Once a patient’s expected maximum oxygen consumption, physical status, safety and test length are factored in it is not clear to me that any one treadmill protocol is better than any other. I am used to the Bruce protocol and think that it worked reasonably well at obtaining an individual’s maximum VO2 but at the same time it probably has too steep a workload profile for debilitated patients. For this reason alone any lab that uses a treadmill for exercise testing should be ready to select from at least a couple different protocols based on the patient’s abilities.

Bicycle ergometers are easier because we use a ramp protocol and all we have to do is select rate at which the workload increases. Even though there are reference equations for an individual’s maximum expected workload however, there is still a bit of guesswork involved. Patients often (usually) underestimate or (less frequently) overestimate their abilities but as long as we get a test that is in the neighborhood of ten minutes or so we are usually satisfied. Even so we all have to work with the equipment we have and there is no reason that good quality cardio-pulmonary exercise tests can’t be performed with either an ergometer or a treadmill.

 

ACIP Protocol, 2-3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	0	2.5
2	2.5	2.0	3.5
3	3.0	3.0	4.5
4	3.0	7.0	6
5	3.0	10.5	7.5
6	3.0	14.0	9
7	3.0	17.5	10.5
8	3.0	21.0	12
9	3.1	24	13.5
10	3.4	24	15

Astrand Protocol, modified, subject selects speed, stage 1: 3 minutes, stage 2-7: 2 minutes

Stage:	Speed (MPH):	Elevation (%):
1	5.0 – 8.5	0
2	5.0 – 8.5	2.5
3	5.0 – 8.5	5.0
4	5.0 – 8.5	7.5
5	5.0 – 8.5	10.0
6	5.0 – 8.5	12.5
7	5.0 – 8.5	15.0
8	5.0 – 8.5	17.5

Balke 3.0 Protocol, 2-3 minute stages

Stage:	Speed (MPH):	Elevation (%):	METS:
1	3.0	0	3
2	3.0	2.5	4
3	3.0	5.0	5
4	3.0	7.5	6
5	3.0	10	7
6	3.0	12.5	8
7	3.0	15	9
8	3.0	17.5	10
9	3.0	20	11
10	3.0	22.5	12

Balke 3.4 Protocol, 2-3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	3.4	2	4
2	3.4	4	5
3	3.4	6	6
4	3.4	8	7
5	3.4	10	8
6	3.4	12	9
7	3.4	14	10
8	3.4	16	11
9	3.4	18	12
10	3.4	20	13
11	3.4	22	14
12	3.4	24	15
13	3.4	26	16

Balke-Ware Protocol, 1 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	3.3	1	4.0
2	3.3	2	4.4
3	3.3	3	4.9
4	3.3	4	5.3
5	3.3	5	5.8
6	3.3	6	6.3
7	3.3	7.0	6.7
8	3.3	8	7.2
9	3.3	9	7.6
10	3.3	10	8.1
11	3.3	11	8.5
12	3.3	12	9.0
13	3.3	13	9.4
14	3.3	14	9.9
15	3.3	15	10.4
16	3.3	16	10.8
17	3.3	17	11.3
18	3.3	18	11.7
19	3.3	19	12.2
20	3.3	20	12.6

Bruce Protocol, 3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
0	1.7	0	2
0.5	1.7	5	3
1	1.7	10	5
2	2.5	12	7
3	3.4	14	10
4	4.2	16	13
5	5.0	18	15
6	5.5	20	18
7	5.5	22	20

Bruce, Low-Level Protocol, 3 minute stages:

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.2	0	2
2	1.2	3	2.5
3	1.2	6	3
4	1.7	6	3.5

CHF (modfied Naughton), 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.0	0	1.5
2	1.5	0	2.5
3	2.0	3.5	3.5
4	2.0	7.0	4.5
5	2.0	10.5	5.5
6	3.0	7.5	6.5
7	3.0	10.0	7.5
8	3.0	12.5	8.5
9	3.0	15.0	9.5
10	3.4	14.0	10.5

Cornell Protocol, 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
0	1.7	0	2
0.5	1.7	5	3
1	1.7	10	5
1.5	2.1	11	6
2.0	2.5	12	7
2.5	3.0	13	8
3.0	3.4	14	10
3.5	3.8	15	11
4.0	4.2	16	13
4.5	4.6	17	14
5.0	5.0	18	15

Costill Protocol, 2 minute stages, can continue past stage 11 as tolerated with 2% increments in elevation.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	8.9	0	7.8
2	8.9	2.0	10.3
3	8.9	4	12.7
4	8.9	6	15.2
5	8.9	8	17.6
6	8.9	10	20.1
7	8.9	12	22.5
8	8.9	14	25.0
9	8.9	16	27.5
10	8.9	18	29.9
11	8.9	20	32.4

Ellestad Protocol, stage 1: 3 minutes, stage 2-7: 2 minutes.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.7	10	5
2	3.0	10	6
3	4.0	10	9
4	5.0	10	10
5	6.0	15	12
6	7.0	15	15
7	8.0	15	17

Gardner-Skinner Protocol, 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	0.0	2.5
2	2.0	2.0	3.1
3	2.0	3.0	3.4
4	2.0	6.0	4.2
5	2.0	8.0	4.7
6	2.0	10.0	5.3
7	2.0	12.0	5.8
8	2.0	14.0	6.4

Gardner-Skinner modified Protocol, 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	0.5	0	1.4
2	1.0	0	1.8
3	1.5	0	2.1
4	2.0	0	2.5
5	2.0	2	3.1
6	2.0	4	3.6
7	2.0	6	4.2
8	2.0	8	4.7
9	2.0	10	5.3

Gerkin Protocol, stage 0: 3 minutes, stages 1-14: 1 minute.

Stage:	Speed (MPH):	Elevation (%):	METS:
0	3.5	0	3.7
1	4.5	0	4.4
2	4.5	2	5.7
3	5	2	6.2
4	5	4	7.6
5	5.5	4	8.2
6	5.5	6	9.8
7	6	6	10.6
8	6	8	12.2
9	6.5	8	13.1
10	6.5	10	14.9
11	7	10	16.0
12	7	12	17.9
13	7.5	12	19.2
14	7.5	14	21.2

HALO Protocol, 4 minute stages.

Stage:	Speed (MPH):	Elevation (%):
0	Self-paced	0
1	“	3.0
2	“	6
3	“	9
4	“	12
5	“	15
6	“	18

Kattus Protocol, 3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	10	5
2	3.0	10	7
3	4.0	10	8
4	4.0	14	10
5	4.0	18	12
6	4.0	22	14

McHenry Protocol, 2-3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	3	3.5
2	3.3	6	6.5
3	3.3	9	7.5
4	3.3	12	9
5	3.3	15	10
6	3.3	18	11.5
7	3.3	21	13.5

Naughton Protocol, 3 minute stages:

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.0	0	2
2	1.5	0	2.5
3	2.0	3.5	3
4	2.0	7.0	4
5	2.0	10.5	5
6	2.0	14.0	6
7	2.0	17.5	7
8	3.0	12.5	8
9	3.0	15	9
10	3.0	17.5	10
11	3.0	20.0	11

Naughton Protocol, modified, stage 1: 4 minutes, stage 2-7 2 minutes.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	0	2.5
2	2.0	3.5	3.5
3	2.0	7.0	4.5
4	2.0	10.5	5.5
5	2.0	14.0	6.5
6	2.0	17.5	7.5
7	2.0	21.0	8.5

Stanford Protocol, 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	3.0	0	3.5
2	3.0	2.5	4.5
3	3.0	5.0	5.5
4	3.0	7.5	6.5
5	3.0	10.0	7.5
6	3.0	12.5	8.5
7	3.0	15.0	9.5
8	3.0	17.5	10.5
9	3.0	20.0	11.5
10	3.0	22.5	12.5

STEEP Protocol, 1 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.5	0	2.1
2	2	0	2.5
3	2	1.5	2.9
4	2	3	3.4
5	2.5	3	3.9
6	2.5	5	4.6
7	2.5	7	5.3
8	3	7	6.2
9	3	9	7.0
10	3	11	7.8
11	3.5	11	9.0
12	3.5	13	10.0
13	3.5	16	11.4
14	4.2	16	13.5
15	5	16	15.9

Taylor Protocol, 3 minute stages, 5-10 minute rest periods between stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	3.5	10.0	8.5
2	7.0	0	6.4
3	7.0	2.5	8.8
4	7.0	5.0	11.2
5	7.0	7.5	13.6

USAFSAM (Modifed Balke-Ware), 3 minute stages:

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	0	2.5
2	3.3	0	3.5
3	3.3	5	6.5
4	3.3	10	8.5
5	3.3	15	10.5
6	3.3	20	12.5
7	3.3	25	15

USAFSAM – slow, 3 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	2.0	0	2.5
2	2.0	5	4
3	2.0	10	5.5
4	2.0	15	6.5
5	2.0	20	8
6	2.0	25	9.5

Weber Protocol, 2 minute stages.

Stage:	Speed (MPH):	Elevation (%):	METS:
1	1.0	0	1.8
2	1.5	0	2.1
3	2.0	3.5	3.5
4	2.0	7.0	4.5
5	2.0	10.5	5.4
6	3.0	7.5	6.4
7	3.0	10.0	7.4
8	3.0	12.5	8.5
9	3.0	15.0	9.5
10	3.4	14.0	10.2

 

References:

Breithaupt P, Adamo KB, Colley RC. The HALO submaximal treadmill protocol to measure cardiorespiratory fitness in obese children and youth: a proof of principle study. Appl Physiol Nutr Metab 2012; 37: 308-314.

Evans CH, White RD editors. Exercise testing for primary care and sports medicine physicians. Published by Springer, 2009

Froelicher VF, Brammell H, Davis G, Noguera I, Stewart A, Lancaster MC. A comparison of the reproducibility and physiologic response to three maximal treadmill exercise protocols. Chest 1974; 65(5): 512-517.

Froelicher VF, Thompson AJ, Davis G, Triebwasser JH. Prediction of maximal oxygen consumption. Comparison of the Bruse and Balke treadmill protocols. Chest 1975; 68(3): 331-336.

Northridge DB, Grant S, Ford I, Christie J, McLenachan J, Connelly D, McMurray J, Ray S, Hnderson E, Dargie HJ. Novel exercise protocol suitable for use on a treadmilll or bicycle ergometer. Br Heart J 1990; 64: 313-316.

Smokler PE, MacAlpin RN, Alvaro A, Kattus AA. Reproducibility of a multi-stage near maximal treadmill test for exercise tolerance in angina pectoris. Circ 1973; 48: 346-351.

Swank AM, Serapiglia L, Funk D, Adams KJ, Durham M, Berning. Development of a branching submaximal treadmill test for predictive VO2 max. J Strength and Conditioning Res 2001; 15(3): 302-308.

Tierney MT, Lenar D, Stanforth PR, Craig JN, Farrar RP. Prediction of aerobic capacity in firefighters using submaximal treadmill and stairmill protocols. J Strength Conditioning Research 2010; 24(3): 757-764.

White RD, Evans CH. Performing the exercise test. Primary Care 2001; 28(1): 29-53.

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

Reports are how patient test results are distributed. Paper versions have become less common because reports are now stored electronically in hospital information systems. Even if the way in which a report’s image is now stored, retrieved and distributed has changed, reports are still generated by our lab’s software systems and the ways in which this is done have not changed in any significant way for quite a while.

Reports are the public face of any pulmonary function lab and they should be designed to be readable and pertinent. It is critically important for any lab to create and manage reports correctly. So why does our lab software make it so hard to do this?

Over the last several months I’ve had the opportunity to compare the reporting systems of the three largest manufacturers of pulmonary function equipment in the US. There are differences of course between each reporting system since each has its own approach towards formatting, editing and printing reports. What they all share however, is a similar underlying model for reports that I call static report pages.

What I mean by static is that the report elements and their position on a report page are determined and fixed in place when the report is formatted. When the report is printed, regardless of whether the results are present or not, the report page does not change. This means that if you format a report to contain spirometry, lung volumes and DLCO, and the only test you perform is spirometry, when you print the report the sections for lung volumes and DLCO will contain no results but they will still appear.

The number of tests that need to be placed on a report will vary from lab to lab depending on what equipment they are equipped with. For example, these tests are available on one manufacturer or another’s test systems:

Spirometry

Lung Volumes – Plethysmography

Lung Volumes – N2 Washout

Lung Volumes – Helium Dilution

Diffusing Capacity

RAW/SGaw

MIP/MEP

MVV

SBN2

6MWT

FOT/IOS

There are probably other tests as well but even if there aren’t, there are other report elements such as demographics, text notes, flow-volume loops, trends etc. that also need to be managed.

A lab could create just one report format that would fit all of the tests it performs but in most instances this report would be at least several pages long (my lab has a report for research studies that has ALL the results from ALL tests and is 14 pages long). A report like this would neither be pertinent nor readable since many of the results would usually be blank. This means that multiple report formats need to be created and maintained. The number of possible combinations of tests can be calculated from 2^N where N equals the number of tests (and this doesn’t include the other report elements such as demographics, text notes, flow-volume loop graphs, trends, etc). There are 11 tests listed, so a lab that performed all of them could have 2^11 or 2048 different possible combinations of tests. Since most labs tend to perform only certain combinations of tests, this is a significant overestimate. Even so, in order to keep our reports pertinent and readable my lab has 12 different report formats and I know of a lab that has over 40 of them.

The first problem with this is that once a set of tests has been performed the lab staff has to choose the right report format. Really? Since the lab software “knows” what tests have just been performed, it also “knows” what tests are included in which report formats. So why isn’t the software able to select the right report format or at least suggest the formats that include the tests that have been performed? The technicians in my lab select report formats reasonably well, but mistakes happen and when they do it can take some time to discover them.

A second problem has to do with modifying or updating report formats. When a change needs to be made, say by something like adding the FEV3/FVC ratio or removing the FEF25-75 from the spirometry results, every single report format that has a section of spirometry results needs to be updated individually. Since the position of all report elements has to be explicitly specified, when one of them is re-sized all of the remaining ones also have to be re-positioned. This means that even simple changes to report formats can be tedious and time-consuming.

[Admittedly, reports usually don’t need to be modified frequently. Even so, the editing software for report formats is at best unsophisticated. I was modifying a report recently and the good thing was that the editing software gave me the option to select from a large number of report elements, the bad thing was that the selection had to be made from a tiny pop-up menu that only showed 4 options out of over 40 at any one moment and I had to spend an inordinate amount of time scrolling back and forth to find what I was looking for.

In addition, although most of the report editors allow you to place elements wherever you want them they also haven’t seemed to have heard of the “snap to grid” function. I work with a variety of graphics programs and several of them allow you to place a grid over your work and then place new elements according to the grid. This makes it easy to line things up. Without a grid, you have to place elements very carefully by eye and hope that they line up.]

The need to create, maintain and select from a large number of report formats is mandated by the decision of our lab equipment manufacturers to use static report pages. I agree that there are situations where the ability to specify the exact location of every report element is advantageous. But for my lab this would apply to only a very small minority of our reports and a better approach would be to use dynamic report pages. We used to have dynamic reports with the DOS version of software we used 15 years ago (newer isn’t always better). Specifically, within the report editor you formatted the specific sections (demographics, spirometry, etc.) and then added them (or not) to the final report format. We actually had only one primary report format at that time, and it had all of the possible tests we performed. When the report was printed only the sections that had results were printed.

There are multiple advantages with a dynamic report format. First, although this doesn’t mean that multiple report formats won’t be needed the number of report formats is substantially reduced. Second, when a report is printed there will never be any blank sections. Third, changes to report sections only have to be made in one place.

So why doesn’t our lab software use dynamic report pages? I really don’t know and I can’t think of a good reason why not. It may be that the feedback our equipment manufacturers have gotten in the past told them that labs wanted static pages. It may be that it is easier to write the software for static report pages (although since DOS-era software was able to print dynamic pages I’m not sure why this would be the case). It may also be that once a decision to go with static report pages has been made, there aren’t sufficient resources to develop more than one type of report.

I’d really prefer to have dynamic report pages and I think that if most PFT labs considered the extra labor that goes into creating, maintaining and selecting static report pages they might well feel the same. Barring that, I’d like to see our lab software at least have the ability to select the most appropriate reports when its time to print one. I would also prefer the ability to format a report section (demographics, spirometry etc) just once, and then place it into a report format.

Finally (although I suspect that the lab equipment manufacturers would disagree) the report formatting and editing functions in our lab software have always seemed to be an afterthought. I agree that reports aren’t something that need constant attention, but even so I’d really prefer to see more sophistication and less tedium in the report editing software we have to work with.

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

I was reviewing PFT reports today and noticed that a patient appeared to have had the wrong gender entered in their demographic information. Specifically, the patient had an unambiguously masculine name but had been entered as female. Just to be sure I checked the patient’s on-line medical record and there he was listed as male. I had noticed from the trend report that the patient had been in the PFT lab numerous times. Since the basic patient demographics (name, date of birth, height, gender, etc.) are automatically forwarded into a new demographics record when a new PFT lab visit is created it struck me as odd that after all this time we had somehow managed to make a mistake with something as basic as gender. For this reason I thought it would be a good idea to see how far back this problem existed and started going back through the patient’s PFT records. About four visits ago the patient’s name suddenly changed to one that was unambiguously feminine.

I was immediately concerned that two different patient’s records had somehow gotten merged. The last time this happened was over 20 years ago and was due to an entry error in the patient ID that was further compounded by how the lab’s software handled new demographic records at the time. Merged records is therefore a symptom of a serious database problem but when I compared the date of birth of the two patients, I was immediately able to see that they were the same. Since this is incredibly unlikely my thought then was that the patient may have had a gender reassignment. When I went back to the patient’s online medical record and searched more carefully, I was able to find that this had occurred over a year ago. This is not the first time we’ve had a transgender patient and so it is an issue we’ve learned how to handle.

So what effect does gender reassignment have on an individual’s pulmonary function test results?

None whatsoever. Gender reassignment by itself does not affect FVC, FEV1, TLC or DLCO. What it does affect is how we interpret the test results and it can also cause some interesting data management problems that are worth noting.

All pulmonary function reference equations differentiate between genders. Although the differences between races and ethnicities is somewhat open to question, there is little doubt about the differences between genders. When individuals with the same height are compared, females universally have lower flow rates, volumes, respiratory muscle strength, gas exchange and oxygen consumption than males. Because lung function is determined during an individual’s childhood and adolescent developmental periods, gender reassignment does not affect lung function and when it is assessed this has to be done using reference equations that are appropriate to an individual’s original gender.

Depending on which way a gender reassignment occurs, results that would be considered normal for a female would likely look reduced for a male, and results that would be considered reduced for a male would likely look normal for a female. The selected gender will therefore make a difference about what an individual’s PFT results look like to a reviewer.

The patient whose gender raised this issue has relatively severe lung disease and is probably not the best example for this, but its what’s in front of me right now.

Female:	Observed:	%Predicted:	Predicted:
FVC:	1.37	42%	3.25
FEV1:	0.92	36%	2.54
FEV1/FVC:	67	84%	80
TLC:	2.69	54%	4.93
RV:	1.34	79%	1.69
DLCO:	14.90	78%	19.12

Male:	Observed:	%Predicted:	Predicted:
FVC:	1.37	37%	3.72
FEV1:	0.92	32%	2.87
FEV1/FVC:	67	87%	77
TLC:	2.69	47%	5.70
RV:	1.34	67%	2.01
DLCO:	14.90	57%	26.05

The male results would be classified as a moderate restrictive ventilatory defect with a coexisting obstructive ventilatory defect and a moderate gas exchange defect. The female results would be classified as a moderate restrictive ventilatory defect with a coexisting obstructive ventilatory defect and a mild gas exchange defect. Not a real big difference, but the percent predicted all of the male results are noticeably lower than the female and I’m certain that for some individual’s whose results are on one threshold or another, this could make a significant difference in how results are interpreted.

Gender really only becomes a problem when it is recorded incorrectly by mistake or omission, or when our data management systems forces us to enter it incorrectly.

Gender can be entered incorrectly every so often (for my lab probably around a half dozen times a year) and for this reason I make a point of checking the patient’s name and gender when I review tests. Many transgender individuals however, are (quite understandably given society’s conflicted and often negative viewpoints on the subject) reluctant to disclose this fact, even to medical staff. Transgenders can also be insistent about identifying themselves as their reassigned gender, again understandably. For these reasons, demographic information can be entered incorrectly because the patient has omitted to provide the correct information.

A more insidious problem however, lies at the intersection between PFT lab databases and a hospital’s information system (HIS). This is a problem my lab had up until the time our HIS interface was last updated, about three years ago. Specifically, when we uploaded test results, the patient’s id number, last name, first name, date of birth and gender were cross-referenced in order to be sure the results were assigned to the correct patient in the hospital information system.

Our problem, therefore, was that if we entered the patient’s original gender in order to get the right predicted values, we weren’t able to upload the test results because the patient’s gender in the PFT lab didn’t match the gender in the hospital information system. If we entered the gender that was in the hospital information system, we didn’t get the right predicted values. The work-around we finally came up with was based on the fact that at that time our interface was based on transferring text files and that the text files were created by one process and uploaded by another. So when it was necessary I would intervene and grab the text file before it was uploaded and manually edit the patient’s gender to match what was in the hospital information system (although to be honest this usually after the interface kicked out an error, not before, but it still got done).

For (some) good and (many) bad reasons gender is not currently an identifying factor with our HIS interface. We are however, in the final planning stages of another revision to our interface with the hospital information system that will (finally!!!) let the physicians electronically sign PFT reports. (Although it is actually more correct to say that we are bystanders in the revision process since almost all of the decisions on how it is going to be implemented are being made by the hospital’s IS department and our equipment/software manufacturer.) At this time it is not clear what identification factors will be used to cross-reference patient records so this may well become a problem again.

There are however, a number of hospital information systems that are very tightly coupled to a PFT lab’s database. In some cases, usually as a function of scheduling, the hospital’s demographic information is used to populate the demographic information in a patient’s PFT database. In these circumstances it’s not clear to me whether gender is an item that can be changed once it has been inserted into the PFT database and if it can be changed, what effect it has on uploading results. I’ve visited labs that have had this kind of a system but this is one item I’ve never thought to check.

It has been estimated that between 2% and 5% of the population have some degree of sexual dysphoria (an unease or dissatisfaction with their gender) but gender reassignment is still a somewhat uncommon process. A related, and very interesting issue however, has to do with individuals born with ambiguous sexual characteristics. Depending on how you want to define it (and there over a dozen different definitions) up to 1 in 100 children are born with ambiguous or intersexual characteristics. Maybe as many as 1 in 1000 children have surgery to “normalize” their genitalia. Many of these individuals do not know they were born this way and many times they never find out. Despite the fact that gender has a significant effect on pulmonary function results I have not found any research that looked at the effect that ambiguous or intersex characteristics may have on the development of lung function. I have to wonder if at least a small part of the variability found when studying pulmonary function in large populations is due to sexual characteristics that are not readily apparent.

The primary problem that we have with managing pulmonary function results for transgender individuals is the dissonance between their “real” and their “assigned” genders. There are physiological reasons for using one, and sociological and psychological reasons for using the other. The real limitation is in our databases and the way we collect demographic information. Gender is always assumed to be only a binary choice (male | female) but as we learn more (and become more open) about human variation (genetically, developmentally and socio-psychologically) a more nuanced approach would probably be more appropriate. One solution would be to have at least two gender choices for an individual, ‘physiological/developmental’ and ‘preferred/apparent’ and this should be applied to both PFT lab and hospital databases.

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

Recently a patient was referred to my lab for a CPET by his oncologist. The patient had been complaining of excessive shortness of breath particularly when climbing only a few stairs. The patient recently had a full PFT panel (spirometry, lung volumes, DLCO) and the results had showed mild restriction with a mild gas exchange defect. The patient’s shortness of breath symptoms were far more severe than could be explained by his PFTs however, so he had been referred to Cardiology and had an ECG stress test. The stress test results were normal so Cardiology told the oncologist that the patient’s problems were probably not cardiac.

Because the patient’s PFT results were reduced the patient’s oncologist consulted with a couple of our pulmonary physicians and they suggested a CPET. When I reviewed the patient’s CPET results despite a mildly reduced TLC and DLCO it was quite clear the patient’s primary limitation was in fact cardiac. Why was there such a discrepancy between Cardiology’s ECG stress test and our CPET? The simple answer is that a CPET measures oxygen consumption and a routine ECG stress test does not.

Strictly speaking, during a progressive exercise test any individual with normal heart and lungs usually reaches a cardiac limit before they reach any kind of a pulmonary limit and this is normal. A fit, athletic individual usually has a higher than normal stroke volume (and cardiac output) while a somebody that is out-of-shape has a reduced stroke volume (and cardiac output). This is one of the key differences between being conditioned and being de-conditioned.

So what are the hallmarks of an abnormal cardiac limitation?

There are, of course, many different types of cardiac disease but the common factor (at least in terms of a CPET) is an abnormal decrease in cardiac output. Cardiac output cannot be measured during exercise without specialized equipment or indwelling catheters but there is an intimate connection between cardiac output and VO2 as shown by the Fick equation:

Note: CaO2 and CvO2 refer to the oxygen content (in vol%) of arterial and venous blood respectively. I’ve frequently seen CaO2 and CvO2 described as the concentration of oxygen in the blood but although this may be semantically correct I feel it is imprecise because it is easily confused with the partial pressure of oxygen or oxygen saturation when it is actually a function of both of these properties:

The Fick equation can be restated to make the relationship more obvious:

A reduced cardiac output will therefore reduce the maximum VO2 but how do you know when a patient has reached their maximum VO2? This occurs when they reach a plateau in their oxygen consumption. This is also the definition of VO2 Max as opposed to the maximum VO2 that is achieved during a CPET. A VO2 plateau usually requires a motivated patient that is willing to endure discomfort and push themselves however, so it is not seen as often as it should be. There isn’t a precise definition for a VO2 plateau and an apparent VO2 plateau during the final moments of a CPET can also occur when a patient has reduced their exercise effort. Because the indicators of patient effort are somewhat subjective my current working definition is a plateau in VO2 that occurs for at least a minute while VCO2 and Ve continue to increase. A VO2 plateau that occurs at a reduced maximum VO2 is a strong indication of a cardiac output limitation.

The maximum VO2 from a CPET can be reduced for non-cardiac reasons, such as pulmonary mechanical or pulmonary vascular limitations (COPD or IPF for example) but in these instances oxygen saturation is also usually reduced. When cardiac output is reduced SaO2 remains normal which is because:

Because pulmonary limitations usually decrease the ability of the lung to transfer oxygen SaO2 will decrease as well but as long as the cardiac output is less than the DLO2 then SaO2 remains normal.

As workload increases during a CPET there comes a point at which the amount of oxygen delivered to the exercising muscle is no longer entirely able to meet its needs. This is the point at which lactic acid begins to accumulate, CO2 production increases and is the definition of the Anaerobic Threshold (AT). A reduced cardiac output reduces the delivery of oxygen to the exercising muscles and for this reason not only is the maximum VO2 decreased when there is a cardiac limitation, the VO2 at anaerobic threshold is also usually reduced.

VO2 at AT:	Male:		Female:
Age:	Mean:	LLN:	Mean:	LLN:
20	53%	42	52%	41
30	54%	43	55%	44
40	55%	44	58%	47
50	56%	45	60%	49
60	57%	46	63%	52
70	58%	47	65%	54

A VO2 at AT that is less than the LLN is a strong indication of an abnormal cardiovacular limitation.

Finally for individuals with normal cardiovascular function, there is a linear relationship between VO2 and workload. For individuals with a low cardiac output, a significant proportion of their energy, particularly above anaerobic threshold comes from anaerobic processes. This means that VO2 decreases more slowly for a given increase in workload.

Depending on the degree of cardiovascular limitation and the motivation of the individual that is exercising this can either be readily apparent or very subtle.

To summarize, an abnormal cardiac limitation usually has these features:

• Reduced maximum oxygen consumption
• Normal SaO2
• Reduced VO2 at anaerobic threshold
• A non-linear VO2-workrate relationship

So what did the patient’s results look like and how do they compare to these benchmarks?

	AT:	%Predicted:	Peak Exercise:	%Predicted:
VO2 (LPM):	0.65	28%	1.17	49%
RER:	0.95		1.40
SaO2:	96%		96%
Minute Ventilation (LPM):	18.4	23%	53.2	64%
Heart Rate (BPM):			115	69%
O2 Pulse (ml/beat):			10.4	72%

In addition:

• There was a VO2 plateau during the final minute of exercise (with an increasing VCO2 and Ve).
• The chronotropic index was 0.72 (0.80 is the LLN).
• Ve/VCO2 at AT was 30.
• Ve-VCO2 slope from rest to AT was 23.6.
• The highest PETCO2 (which occurred slightly after AT) was 39.9.
• There was a slight downwards inflection of the VO2-workload starting around AT

The RER of 1.40 and VO2 plateau indicates that this was truly a maximal CPET. The low VO2 at anaerobic threshold and low VO2 max without a decrease in SaO2 indicates that the primary limitation was cardiovascular.

The CPET shows at least two reasons for a cardiovascular limitation; One part is chronotropic incompetence (as shown by the reduced chronotropic index, the patient was taking Metoprolol and it’s possible the dosage is too high). The other part is a reduced stroke volume (as shown by the reduced maximum O2 pulse). There are likely other cardiac issues but these are the ones the CPET makes definitive.

It was also clear there were no pulmonary limitations. The minute ventilation of 23% of predicted at AT and maximum minute ventilation of 64% of predicted indicates there wasn’t any pulmonary mechanical limitation. The normal Ve/VCO2 at AT, Ve-VCO2 slope and PETCO2 indicate that there wasn’t pulmonary vascular limitation.

An abnormal cardiac limitation isn’t necessarily accompanied by ECG changes that can be detected with a stress ECG test. Rightly or not, the oncologist felt that they and the patient had been blown off by cardiology. In this instance my PFT lab was able to give a fairly definitive answer for the patient’s shortness of breath but I’d like to stress that what we performed was a cardio-pulmonary exercise test.

CPETs are highly effective at determining the causes for shortness of breath. In many instances, given that it is non-invasive, it is the only reasonable approach as well. Unfortunately cardiopulmonary exercise tests are not as commonly available as they should be. Even when they are available, CPETs are not ordered as frequently as they should be. For these reasons there are many patients with shortness of breath who are forced to go for a prolonged time without a diagnosis and may be end up being “blown off” by any number of specialists.

To a large extent this is a cart and horse problem. Patients don’t have CPETs ordered because they aren’t readily available and CPET programs are not supported because there aren’t enough patients. I could (and frequently do) argue that CPET (and PFT) testing is a solution for institutional cost-effectiveness because it improves patient care with earlier and better diagnoses but producing the numbers to back this up is difficult. Realistically this means that any good CPET program requires a commitment from a hospital’s physicians and administrators who are willing to believe in the effectiveness of CPET testing without being able to prove it.

Cardiopulmonary exercise tests are quite good at differentiating between the pulmonary and cardiac causes of an exercise limitation. In this case, despite a reduced TLC and DLCO and a normal ECG stress test, the patient’s limitations were ultimately due to a cardiac rather than a pulmonary limitation. In one sense this proves the value of cardiopulmonary exercise testing but I also want to take this as a reminder that patients are complex and that the tests we use most routinely always have a limited scope.

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

The static respiratory pressures, Maximal Inspiratory Pressure (MIP or PIMAX) and Maximal Expiratory Pressure (MEP or PEMAX) are a way to non-invasively assess respiratory muscle strength. Respiratory muscle weakness is present in a number of conditions, most notably neuromuscular diseases and disorders, but also malnutrition, cardiovascular disease, polymyositis, sarcoid and COPD. Strictly speaking, the maximal inspiratory and expiratory pressures are not generated solely by the respiratory muscles but also by the elastic recoil. The elastic recoil of the lung at TLC contributes up to 40 cm H2O towards MEP and the elastic recoil of the chest wall at RV contributes up to 30 cm H2O towards MIP. Even so, an individual cannot reach TLC or RV without the use of their respiratory muscles so the measurements are still valid regardless of how the pressures are generated.

I have mixed feeling about MIPs and MEPs but this is mostly because many patients perform these tests poorly, making it hard to interpret results. Normal results can rule out respiratory muscle weakness but reduced results are not necessarily diagnostic. Nevertheless, they are still valuable tests and it is important for them to be performed correctly.

MIP is measured at RV and MEP is measured at TLC. The ATS/ERS statement on respiratory muscle testing indicates that each effort should last at least 1.5 seconds and that at least three measurements within 20% of the highest value should be obtained. A maximum number of attempts has not been specified but most research studies limited this to 5 or 6.

The actual maneuver depends somewhat on the equipment configuration. Respiratory pressures were originally measured using a pressure gauge and most early systems consisted of just a mouthpiece and a gauge (or gauges).

To use this type of system the patient either exhales to RV or inhales to TLC, places their lips around the mouthpiece and then forcefully inhales or exhales. Because of the limited amount of time available for lip placement a round plastic or cardboard mouthpiece is usually used.

Currently, most MIP-MEP mouthpiece manifolds have a side hole that the patient can breathe through prior to performing a MIP or MEP maneuver.

This allows the use of a flanged mouthpiece which usually takes longer to insert and seat properly inside a patient’s mouth. With these types of manifolds the patient is placed on the mouthpiece first and allowed to breath normally until they are instructed to exhale to RV or inhale to TLC. The technician then blocks the hole and the patient then forcefully inhales or exhales. After the measurement the technician unblocks the hole and allows the patient to return to normal breathing.

Regardless of what type of a mouthpiece system is used a small leak must be built into it. This is intended to prevent glottal closure and the use of cheek muscles. The ATS/ERS statement specifies a hole with a 2 mm internal diameter that is 20-30 mm long (the length gives the leak a controlled resistance).

Although a side-hole manifold can be used with a pressure gauge the ATS/ERS standard makes the use of an electronic pressure transducer more or less mandatory. There are a couple reasons for this. First, reading pressure off a gauge during the relatively short time a patient inhaling or exhaling can be difficult. Although there are recording gauges (a secondary needle that is moved by the primary needle and remains at the highest pressure until reset) what is most likely to be reported is the peak pressure and that is not necessarily what is supposed to be recorded. Instead of the peak pressure (which could be a spike lasting only a short time), the ATS/ERS standards state that the maximum pressure should be averaged over a 1 second period and this is not possible with a gauge. Averaging requires an electronic pressure transducer and a computer with software designed to analyze the pressure signal and perform the averaging.

I have been unable to find any study that looked at the difference between peak and averaged MIP and MEP measurements. Since the point of the MIP and MEP tests are to measure respiratory muscle strength averaging is probably the best way to reject transient pressure spikes. The 1 second averaging period is relatively arbitrary and some studies have used different averaging periods, but since the averaging of MIP and MEP waveforms has not been studied in detail its not clear if there is an optimum averaging period.

More importantly though, the ATS/ERS statement only specifies that a 1-second average should be computed, not how it should be computed. This leaves it to individual researchers and manufacturers to decide how to implement an averaging algorithm. Presumably the peak MIP or MEP is used to select the proper segment of data for an averaging algorithm, but its not clear how much data before or after the peak pressure should be averaged. When I review the MIP and MEP results from our test systems it is unclear what part of the pressure waveform is being averaged (or should be averaged for that matter).

It also depends on how an algorithm is written whether a short effort (<1 second; which is admittedly a suboptimal effort but may also be the best the patient can do) will be underestimated or not. This may or may not make a significant difference in the reported MIP or MEP but it should be addressed the next time the ATS/ERS updates their standards.

Interestingly, several studies have shown that patients tend to get higher MIP and MEP pressures with a simple round mouthpiece than with a flanged mouthpiece. The reasons for this are unclear but the ATS/ERS statement nevertheless recommends a flanged mouthpiece which is because “These mouthpieces are also easier for patients to use, especially those with neuromuscular disease.”

So once you’ve gotten good quality MIP and MEP measurements, what’s normal?

The predicted values for both MIP and MEP decrease with age and are larger for males than for females. Interestingly, height and ethnicity are not significant factors in most or all MIP and MEP reference equations. Unlike most other pulmonary function tests weight in one form or another (i.e. BSA or BMI) is a significant factor in most MIP and MEP reference equations. Not surprisingly, increased weight increases the predicted MEP in most instances. Somewhat surprisingly however, increasing weight also usually increases the predicted MIP. The reason for this relationship was not generally discussed except for one researcher who attributed it to an increased diaphragmatic strength.

As with many pulmonary function tests the normal values for MIP and MEP are spread over a relatively large range, and as usual selecting a single set of reference equations is problematic. The studies with the largest populations are limited to older individuals (45-85) and the studies with the widest age ranges were performed on relatively small populations. Because it’s particularly difficult to make a nuanced interpretation of MIP and MEP (basically all you can say is normal or abnormal) in this particular instance I’d recommend looking at the lower limit of normal instead.

The ATS/ERS standard states that a “PIMAX of -80 cm H2O usually excludes clinically important inspiratory muscle weakness”. This statement isn’t referenced to any study however, and is not necessarily supported by research data. Evans et al performed an extensive analysis of the LLN for MIP and MEP and developed several reference equations which seem pretty reasonable.

	Male:	Female:
MIP LLN:	62 – (0.15 x age)	62 – (0.50 x age)
MEP LLN:	117 – (0.83 x age)	95 – (0.57 x age)

MIP and MEP are useful tests for assessing respiratory muscle strength that can be performed with relatively simple equipment. They are particularly useful for monitoring patients with known neuromuscular diseases and disorders. They should also be performed when patients with otherwise normal pulmonary function tests continue to complain of dyspnea and exercise intolerance.

MIP and MEP are very effort-dependent test and more than one study has indicated that a properly trained technician can make a significant difference in a patient’s test results. Patients need to be encouraged properly and particularly since these tests are frequently ordered for patients with neuromuscular diseases their lips and mouth needs to be checked during the test for a proper seal. For those patients that are unable to maintain a tight seal it may be possible to substitute a mask. Mask and mouthpiece MIPs and MEPs have been studied in normal subjects and although mask pressures were less than those obtained by mouthpiece the difference was not statistically significant.

MIP and MEP testing requires only relatively simple and inexpensive equipment. Many lab testing systems come equipped to perform MIP and MEP testing without the need to order it as an additional option. There is no CPT4 code for MIP and MEP testing however, (we use 94799, unlisted service) and some insurance companies will not pay for testing. I’ve read that some PFT labs don’t perform MIPs and MEPs for this reason but there are several tests we routinely perform (supine spirometry, for example) that we aren’t fully reimbursed for. I think this is just part of taking care of our patients, but the decision to offer or not to offer specific tests is sometimes made by hospital administration, not the lab.

Male:	MIP Reference Equations:
Source:	Equation:
[A]	143 – (0.55 x age)
[B]	2.71828183^(4.02 – (0.004 x age) + (0.47 x BSA))
[C]	161 – (0.99 x age)
[D]	149 – age + (0.1 x wt_lb)
[G]	126-(1.028 x age) + (0.343 x wt_kg)
[H]	10.2 x (0.158 x BMI) – (0.051 x age) + 8.22)
[I]	155.3 – (0.80 x age)
[J]	9.8-(0.31 x age)+(1.47 x wt_lb) – (0.0026 x (wt_lb^2)) – (0.0059 x age x wt_lb)
[K]	142 – (1.03 x age)

Female:	MIP Reference Equations:
Source:	Equation:
[A]	104 – (0.51 x age)
[B]	2.71828183^(3.76 – (0.004 x age) + (0.47 x BSA))
[D]	118 – (0.9 x age) + (0.1 x wt_lb)
[G]	171 – (0694 x age) + (0.861 x wt_kg) – (0.743 x ht_cm)
[H]	10.2 x (8.55 – (0.24 x age))
[I]	110.4 – (0.49 x age)
[J]	-388+(1.77 x age)-(0.014 x (age^2))+(wt_lb x 0.41)-(0.0041 x age x wt_lb)+(4.69 x ht_cm)-(0.014 x (ht_cm^2))
[K]	(0.71 x ht_cm) – 43

Male:	MEP Reference Equations:
Source:	Equation:
[A]	268 – (1.03 x age)
[B]	2.71828183^(4.48 – (0.0004 x age) + (0.25 x BSA))
[C]	215 – (0.43 x age)
[D]	278 – (2.27 x age) + (0.28 x wt_lb)
[I]	165.3 – (0.81 x age)
[K]	180 – (0.91 x age)

Female:	MEP Reference Equations:
Source:	Equation:
[A]	170 – (0.53 x age)
[B]	2.71828183^(4.3 – (0.0004 x age) -(0.003 x age) + (0.25 x BSA))
[D]	179 – (1.68 x age) + (0.36 x wt_lb)
[I]	115.6 – (0.61 x age)
[K]	3.5 + (0.55 x ht_cm)

MIP/MEP Study Populations:

Source:	#male	age range	#female	Age Range:	Ethnicity:
[A]	60	20-74	60	20-74	Not specified
[B]	266	18-70	359	18-70	Not specified
[C]	101	20-59			Caucasian
[D]	112	65-85	176	65-85	Not specified
[E] MEP	329	65-85	427	65-85	96% Caucasian, 4% Black
[E] MIP	2259	65-85	2942	65-85	96% Caucasian, 4% Black
[F]	n/a			n/a	Synthesized from other studies
[G]	139	20-90	128	20-90	Not specified
[H]	248	18-82	256	18-82	Not specified
[I]	50	20-80	50	20-80	Brazilian
[J]	1886	45-84	1963	45-84	White, Black, Asian, Hispanic
[K]	48	18-50	87	18-50	Caucasian

MIP/MEP Study Methods:

Source:	Year:	Measured By:	Mouthpiece	Sample:
[A]	1969	Gauge	Rubber, round	Peak
[B]	1992	Transducer	Plastic, oval	Peak
[C]	1987	Transducer	Plastic, round	Peak
[D]	1995	Transducer	Cardboard, round	Peak
[E] MEP	1994	Gauge	Rubber, flanged	0.5 sec averaged
[E] MIP	1994	Gauge	Plastic, round	0.5 sec averaged
[F]	2009	n/a	n/a	n/a
[G]	1998	Transducer	Cardboard, round	2 sec Plateau
[H]	2000	Transducer	Rubber, round	2 sec Plateau
[I]	1999	Guage	Plastic, flanged	1 sec
[J]	2009	Gauge	Cardboard, round	Visually averaged, rounded to nearest 5 cmH2O
[K]	1984	Gauge	Plastic, flanged	1 sec, Peak

References:

ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med 2002; 166: 518-624.

[A] Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationship to age and sex. Am Rev Respir Dis 1969; 99: 696-702.

[B] Bruschi C, Serveri I, Zoia MC, Fanfulla F, Fiorentini M, Casali L, Grassi M, Grassi C. Reference values of maximal respiratory mouth pressures: A population-based study. Am Rev Respir Dis 1992; 146: 760-793.

[C] Cordain L, Glisan BJ, Latin RW, Tucker A, Stager JM. Maximal respiratory pressures and pulmonary function in male runners. Brit J Sports Med 1987; 21(2): 18-22.

[D] Enright PL, Adams AB, Boyle PJ, Sherill DL. Spirometry and maximal respiratory pressure references from health Minnesota 65 to 85-year-old women and men. Chest 1995; 108: 663-669.

[E] Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt RE. Respiratory muscle strength in the elderly. Correlates and reference values. Am J Respir Crit Care Med 1994; 149: 430-438.

[F] Evans JA, Whitelaw WA. The assessment of maximual respiratory mouth pressure in adults. Respir Care 2009; 54(10): 1348-1359.

[G] Harik-Khan RI, Wise RA, Fozard JL. Determinants of maximal inspiratory pressure. Am J Respir Crit Care Med 1998; 158: 1459-1464.

[H] Hautmann H, Hefele S, Schotten K, Huber RM. Maximal inspiratory mouth pressures (PIMAX) in healthy subjects – what is the lower limit of normal? Respir Med 2000; 94: 689-693.

McElvaney G, Blackie S, Morrison NJ, Wilcox PG, Fairbarn MS, Pardy RL. Maximal static respiratory pressures in the normal elderly. Am Rev Respir Dis 1989; 139: 277-281.

[I] 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.

[J] Sachs MC, Enright PL, Hinckley Stukovsky KD, Jiang R, Barr RG. Performance of maximum inspiratory pressure tests and maximum inspiratory pressure reference equations for 4 race/ethnic groups. Respir Care 2009; 54(10): 1321-1328.

[K] Wilson SH, Cooke NT, Edwards RHT, Spiro SG. Predicted normal values for maximal respiratory pressures in caucasian adults and children. Thorax 1984; 39: 535-538.

Wohlgemuth M, van der Kooi EL, Hendriks JC, Padberg GW, Folgering HT. Face mask spirometry and respiratory pressures in normal subjects. Eur Respir J 2003; 22: 1001-1006.

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

I was reading James Hansen’s textbook on pulmonary function testing (one of my more interesting reads lately) and in passing he mentioned using the VA/TLC ratio as a way to measure ventilation inhomogeneity. The VA/TLC ratio has also been called the Va,eff/VA ratio and the VA’/VA ratio by different researchers but regardless of what it is called it is the ratio between a single-breath TLC measurement (VA) taken from a DLCO test and a multi-breath (helium dilution or N2 washout) or plethysmographic TLC.

A single-breath TLC regardless of whether helium, nitrogen, methane or argon is used tends to underestimate TLC even in individuals with normal lungs (and if the ratio > 1.0 then there is likely a technical problem with either the lung volume or DLCO measurements). This is mostly because of the limited time a single breath of tracer gas has to mix and diffuse evenly throughout the lungs. The idea is that a low VA/TLC ratio indicates poor gas mixing and therefore an elevated ventilation inhomogeneity.

The VA/TLC ratio is a relatively simple approach towards measuring ventilation inhomogeneity largely because the results can be derived from regular TLC and DLCO measurements. It was first proposed as a measurement over 40 years ago but despite having several notable proponents it has not achieved any particular level of acceptance.

Part of the reason for this may be that there is limited agreement about what a constitutes a normal VA/TLC ratio. Cotes et al suggest that the ratio decreases slightly with age and stated that the normal range is 0.9 to 1.0 at age 20 and 0.85 to 0.95 at age 60. Roberts et al, however, in a study with a reasonably large population (n=379) selected for the presence or absence of certain conditions (normal, asthma, COPD) found no particular correlation with age (or height, weight and gender) and stated that in individuals with normal FEV1/FVC ratios the LLN was 0.828. Punjabi et al in a retrospective study of 5369 individuals unselected except for the presence of acceptable test quality stated that for FEV1/FVC ratios above 0.70 the VA/TLC ratio was 0.98.

There is general agreement however, that the strongest correlation between TLC and VA is an individual’s FEV1/FVC ratio.

Ventilation inhomogeneity is a consequence of airway obstruction. As COPD progresses from mild to severe obstruction, FEV1 decreases and RV tends to increase. About 45 years ago Cotes proposed an Obstruction Index that combined the FEV1, RV and the VA/TLC ratio:

The normal range for the Obstruction Index is 20-40. With severe airway obstruction it increases to 80 and with pulmonary fibrosis it decreases to 10. Although this index never gained any acceptance it is still an interesting notion and it does combine many of the features that are still used to assess airway obstruction.

Roberts et al studied the repeatability of the VA/TLC measurement and showed the coefficient of variance to be 7.3%. The repeatability of lung volume measurements have been studied several times and the coefficient of variance for TLC measurements ranges from 2.2% to 4.25%. The repeatability of DLCO measurements has been studied several times but the repeatability of VA has unfortunately not been studied at the same time so its coefficient of variance is unknown. Although the coefficient of variance for the VA/TLC is larger than that for TLC, it probably what would be expected if VA had a coefficient of variance similar to TLC.

At the present time there are no standards for VA performance and quality. The DLCO (and VA) measurement requires an individual to exhale to RV and then inhale to TLC. The ATS/ERS statement for DLCO testing states that the inspired volume should be at least 85% of the FVC. This however, is based on research that has shown that DLCO measurements are relatively constant near TLC and it is unclear that this criterion is adequate for VA. Even if the inspired volume is 85% of the FVC, VA can be underestimated if the inspiration is not to TLC since the lung will not be fully expanded. VA may also be underestimated when the inspiration is to TLC if an individual does not full exhale to RV first because the inhaled gas mixture may not be evenly distributed during the inhalation.

The researchers that have studied VA/TLC have usually set reasonably high quality standards for their TLC and VA measurements and have been able to reject measurements that don’t meet quality criteria. Although PFT Lab are also interested in test quality when routine clinical lung volume and DLCO measurements are made, results are still have to be reported from patients that have difficulty meeting these same standards. For these reasons the clinical use of the VA/TLC ratio should probably be limited to those times when duplicate lung volume and DLCO measurements that meet the ATS/ERS standards for quality and repeatability have been performed.

Regardless of the quality and repeatability issues the biggest and perhaps most insurmountable problem with the VA/TLC ratio measurement is that VA is calculated from an alveolar sample that is optimized for DLCO measurement. For individuals with relatively normal lungs the inhaled gas mixture is homogeneously mixed and the measured VA is similar regardless which part of the alveolar sample is used to calculate it.

But in individuals with severe airway obstruction, the inhaled gas mixture is inhomogeneously mixed and during exhalation the tracer gas concentration decreases throughout exhalation.

This means that the calculated VA depends greatly on the size of the exhaled sample and where exactly in the exhalation it is taken.

Even if the washout and sample volume are rigorously controlled this aspect alone calls into question exactly what the VA/TLC ratio is measuring.

I’m interested in ventilation inhomogeneity since it is has the potential to be an important component in the assessment of airway obstruction. Clinicians have long noted that individuals with identical levels of airway obstruction often have very different levels of dyspnea and physical impairment. Similarly, individuals with COPD and asthma report changes in how well they feel that often occur without any apparent change FEV1 or Peak Flow. In both of these instances the changes and differences may be explained by other factors, one of which is the degree of ventilation inhomogeneity.

Even though it is an important aspect of lung disease, there is a lack of consensus in how ventilation inhomogeneity should be measured. Several tests have been used to measure ventilation inhomogeneity, notably the Lung Clearance Index (LCI), phase III of the single-breath N2 washout and the VA/TLC ratio. These tests have only rarely been compared to each other and for this reason their comparative sensitivity, accuracy and relevance is unclear.

Finally, the concept of ventilation inhomogeneity itself suffers from a lack of precision. FVC, FEV1, Peak Flow and other pulmonary function measurements have a basis in physical measurements such as volume and flow that permits them to be compared relatively precisely to normal values, to trended values and to other individuals. Although test for ventilation inhomogeneity have numerical results they can only be assessed qualitatively (good, fair, poor) and this is a significant limitation to its utility in both research and clinical care.

The VA/TLC ratio has the potential to provide information about gas mixing and ventilation inhomegeneities within an individual’s lung and I have occasionally used it as a teaching point when explaining pulmonary function tests to physicians and technicians. Its usefulness is severely limited however, partly because the level of accuracy of the VA/TLC ratio from routine lung volume and DLCO measurements is unclear, partly because the VA measurement is made using a washout and sample volume optimized for a different test and partly because results cannot be reported quantitatively. As interesting as it may be, I have trouble seeing how the VA/TLC ratio provides any clinically useful information to the assessment of an individual’s pulmonary function tests.

References:

Burns CB, Scheinhorn DJ. Evaluation of single-breath helium dilution total lung capacity in obstructive lung disease. Am Rev Resp Dis 1984; 130: 580-583.

Cotes JE. Lung volume indices of airway obstruction. A suggestion for a new combined index. Proc R Soc Med 1971; 64: 1232-1234

Cotes JE, Chinn DJ, Miller MR. Lung Function. Physiology, measurement and application in medicine. Sixth Edition, Blackwell Publishing, 2006.

Hankinson JL, Stocks J, Peslin R. Reproducibility of lung volume measurements. Eur Respir J 1998; 11: 787-790.

Hansen JE. Pulmonary function testing and interpretation. Jaypee Brothers Medical Publishers, 2011.

Loiseau A, Loiseau P, Saumon G. A simple method for correcting single-breath lung capacity for underestimation. Thorax 1990; 45: 873-877.

Loves RG, Attfield MD, Isles KD. Reproducibility of pulmonary function tests under laboratory and field conditions. Brit J Indust Med 1980; 37: 63-69.

Pesola GR, Magari RT, Dartey-Hayford S, Coelho-D’Costa V, Chinchilli VM. Total lung capacity: single breath methane dilution versus plethysmograph in normals. Respirology 2007; 12: 291-294.

Punjabi NM, Shade D, Wise RA. Correction of single-breath helium lung volumes in patients with airflow obstruction. Chest 1998; 114: 907-918.

Roberts CM, MacRae KD, Seed WA. Multi-breath and single breath helium dilution lung volumes as a test of airway obstruction. Eur Respir J 1990; 3: 515-520.

Rodarte JR, Hyatt RE, Westbrook PR. Determination of lung volume by single- and multiple-breath nitrogen washout. Am Rev Resp Dis 1976; 114: 131-136

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

Recently I reviewed a set of completely irreproducible spirometry results. The patient had made eight attempts and the FVC, FEV1 and Peak Flow were different every time. In particular, there were frequent stops and starts during exhalation. I’ve always wondered why some patients have so much difficulty with what should be a simple test and although in this particular case it could simply be glottal closure I wondered if it could be Vocal Cord Dysfunction (VCD). For this reason I spent some time reviewing the literature.

Vocal Cord Dysfunction is defined as the paradoxical closure of the vocal cords with variable airflow obstruction that often mimics asthma and in fact VCD is often mistaken for refractory asthma. Unfortunately, for this reason individuals with VCD are often treated with corticosteroids and bronchodilators for years without any improvement of their symptoms.

The gold standard for diagnosing VCD is direct visualization of the vocal cords with a laryngoscope. Characteristically, the anterior (frontal) two-thirds of the vocal cords are closed with a narrow posterior glottal chink. The difficulty with this is that VCD symptoms are often transitory and a large number of patients that are suspected to have VCD are asymptomatic when a laryngoscopy is performed.

Since most PFT labs are not equipped with laryngoscopes nor are they prepared to perform a laryngoscopy at a moment’s notice we have to rely on the tests that measure airflow. Although the wheeze and shortness of breath that accompanies VCD mimics asthma the most common problem associated with VCD is inspiratory obstruction. The flow-volume loop pattern is therefore that of a variable extrathoracic airway obstruction.

Many individuals with VCD have reduced inspiratory flows with an elevated MEF@50%/MIF@50% ratio even when not symptomatic. Because the inspiratory obstruction is primarily in the vocal cords and not the airways most individuals with VCD do not have a significant response to bronchodilators. Because of the inspiratory obstruction, symptomatic individuals with VCD tend to have an MVV that is reduced well below the expected FEV1 x 40.

Although VCD is usually described as being primarily an inspiratory obstruction some individuals with VCD have expiratory instead of inspiratory obstruction, and many have both inspiratory and expiratory obstruction. When expiratory obstruction occurs it causes the flow-volume loop and spirometry to mimic results that would be seen in mild to moderate airway obstruction.

Some researchers have indicated that VCD is associated with a hyper-reactive upper airway and have shown that VCD symptoms can be elicited during methacholine, exercise and cold air challenges. The primary goal of these tests is usually to assess decreases in FEV1 but for VCD it is an increase in inspiratory obstruction that is important. For this reason, an individual with VCD can become symptomatic during a challenge test but often do not show a significant change in FEV1.

Although most individuals with VCD do not have a significant response to bronchodilators it is possible to have both VCD and asthma and at least one study reported an incidence of asthma with VCD in 55% of their study population although most studies have reported a much smaller proportion.

When airway resistance is measured symptomatic individuals with VCD have a fairly distinct Raw loop that shows an inspiratory flow plateau. Raw in general is also usually elevated.

Some researchers have suggested that there are two distinct types of VCD: spontaneous and exercise-induced. Spontaneous VCD occurs without any specific precipitating factors. It is usually not triggered by exercise and can occur at any time. Exercise-induced VCD is usually only precipitated by exercise and individuals are usually symptomatic only during exercise. When tidal loops are obtained during exercise in individuals with exercise-induced VCD they often show a flattening in both inspiratory and expiratory flows. One case study indicated that a inspiratory sawtooth pattern also appeared during exercise.

Vocal cord dysfunction occurs for a variety of reasons and the one that is most commonly put forward is that it has psychogenic causes, and to some extent this may well be true. A significant number of individuals with VCD have anxiety and personality disorders. As well as exercise however, VCD is also associated with gastro-esophageal reflux disease (GERD), chronic rhinosinusitis, inhaled irritants (ammonia, chlorine, cleaning fluids, smoke) and certain neurologic disorders.

VCD also occurs post-operatively and this has been attributed to the possible trauma of the vocal cords during intubation, trauma from inflation of the tracheal cuff and nerve injury from central venous cannulation. Post-op VCD has been severe enough to require re-intubation and even tracheostomy in some cases.

The incidence of VCD is unclear. Different studies have variously reported that 2.5%, 2.8%, 9.5%, 15% and 22% of subjects with stridor and/or dyspnea referred to their studies have VCD but how common it is in the general population has never been estimated. VCD appears to be more common in females than in males and the ratios of female to male in study populations has been reported to be between 2:1 and 3:1.

The report that got me to thinking about VCD showed primarily irreproducible spirometry with mostly truncated expiratory efforts. Inspiratory flows, when they were captured, were relatively normal. When spirometry efforts are discussed in the VCD literature, inspiratory obstruction has been the most commonly reported feature but most researchers have also indicated that this is variable and that often not even a majority of their study population shows this. Occasionally, the irreproducibility of spirometry results has been noted in passing and one case study noted frequent glottal closure, but this aspect hasn’t been studied in any detail so it’s not clear just how reproducible or irreproducible spirometry in individuals with VCD actually is. A related question would be whether irreproducibility or particular forms of irreproducibility are in themselves a potential indication of VCD. So does did this particular patient have VCD? I’d say it was certainly possible but it’s just not possible to be certain from the spirometry results alone.

VCD should be considered as a potential diagnosis for patients that appear to have asthma but do not respond to treatment with bronchodilators and corticosteroids. Despite being a somewhat variable aspect inspiratory obstruction is the primary feature seen in patients with symptomatic VCD. For this reason care needs to be taken when performing spirometry to include a good inspiratory maneuver (particularly during challenge testing). Individuals with VCD tend to show airway obstruction mostly when symptomatic however, and an actual diagnosis of VCD is multi-factorial. Although spirometry (and other pulmonary function tests) can suggest the presence of VCD, they are not in any way definitive.

References:

Deckert J, Deckert L. Vocal cord Dysfunction. Am Fam Physician 2010; 81: 156-159.

Doshi DR, Weinberger MM. Long-term outcome of vocal cord dysfunction. Ann Allergy Asthma Immunolo 2006; 96: 794-799.

Goldman J, Muers M. Editorial: Vocal cord dysfunction and wheezing. Thorax 1991; 46: 401-404.

Haverkamp H, Miller J, Rodman J, Romer L, Pegelow D, Santana M, Dempsey J. Extrathoracic obstruction and hypoxemia occurring during exercise in a competitive female cyclist. Chest 2003; 124: 1602-1605.

Kenn K, Balkissoon R. Vocal cord dysfunction: what do we know? Eur Respir J 2011; 37: 194-200.

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

I was reviewing a spirometry report and noticed something odd about the flow-volume loop, or more specifically the tidal loop, and this got me to thinking about what tidal loops can tell us about test quality, patient physiology and the ability of the technician to coach a spirometry test.

There are at least a couple things wrong with this FVC test effort. First the exhalation time was only about 3 seconds so the FVC volume was likely underestimated by a fair amount. Second, it wasn’t reproducible and this was actually the patient’s the best test effort. What I noticed however, was that the tidal loop was shifted almost completely to the left.

There are a number of criteria for assessing the quality of a forced vital capacity. Exhalation quality can be determined reasonably well by back extrapolation, expiratory time and the terminal expiratory flow rate. When it comes to assessing the completeness of the inspiration that precedes the exhalation however, there really isn’t much to go on other than the reproducibility of an individual’s spirometry efforts.

When I measured the tidal loop what I saw was that IRV was about 0.10 L and the ERV, although likely underestimated by a fair amount, was at least 0.80 L. What I actually think this tidal loop is saying is that the patient didn’t take as deep a breath as they could at the start of the test, but what other things could affect the position of the tidal loop?

For an individual with normal lungs, the IC is usually around twice the volume of the ERV.

Body weight can affect the position of the tidal loop. Because of the compressive effect an increase in body weight has on the thorax FRC tends to decrease when BMI increases. This moves the tidal loop closer to RV, thereby increasing IC and decreasing ERV. A low body weight has somewhat the opposite effect and FRC tends to increase slightly as BMI decreases.

Not all individuals with tidal loops shifted rightwards towards RV are overweight, but many individuals that are overweight will have a rightwards shifted tidal loop. In this instance at least, the position of the tidal loop says something about an individual’s physiology.

Regardless of an individual’s BMI however, a rightwards-shifted tidal loop means that tidal breathing is occurring where an expiratory flow limitation is more likely. In addition because it is on a less favorable portion of the pressure-volume curve, the work of breathing is higher when tidal breathing is near RV and these may be a factors in some patients’ sensation of dyspnea.

The expiratory flow limitation that accompanies severe COPD causes gas trapping and hyperinflation. FRC increases, IC decreases and the tidal loop tends to shift leftwards toward TLC.

The leftwards shift that is due to airway obstruction is often offset by a decrease in FVC which can keep the tidal loop more or less centered until the obstruction is extremely severe. Regardless, when tidal breathing is shifted towards TLC it is also on an inefficient portion of the pressure-volume curve of the lung. The elevated work of breathing and limited ability to increase tidal volume are factors that increase dyspnea in patients with COPD.

Spirometry has a psychological as well as a physiological aspect. The maneuvers required for the correct performance of a spirometry effort are often not familiar to patients and for this reason they often need coaching. An important aspect of a PFT technician’s job therefore, is to properly lead a patient through testing and this also means cuing them at the right time.

When a patient is cued at the wrong time they can be unprepared to take a full inspiration and the quality of the effort can be reduced. Noting where the full inspiratory effort began can be a clue about how well a technician is coaching patients, particularly when it occurs in more than one test effort and more than one patient.

The tidal loop is often unnoticed and underutilized. Tidal loops can be shifted rightwards toward RV because of obesity and leftwards towards TLC because of airway obstruction. A tidal loop that is shifted towards RV or TLC when neither of these conditions is present may in fact be giving us an important diagnostic clue or a clue about test quality instead.

There are no ATS/ERS criteria for the tidal loop and attempts in the past to use the tidal loop diagnostically have been largely unsuccessful because tidal breathing is often inconsistent and irreproducible. There are also good reasons why IC and ERV are measured from a slow vital capacity maneuver instead of a forced vital capacity. This doesn’t mean that a tidal loop can’t provide additional information about the patient.

The spirometry efforts from my lab and from several other labs I am familiar with usually contain one or more tidal breaths. I was reminded that this is not a given however when I reviewed a report shown to me by a friend that not only had no tidal loops but no inspiratory loops either. When I took a close look it was evident from the way the graphic was formatted that is was in fact only possible for the expiratory flow-volume curve to be shown. I will agree that FEV1, FVC, Peak Flow, and the FEV1/FVC ratio all come from the expiratory part the spirometry maneuver and I can understand why a manufacturer or lab might want to simplify a spirometry report but I think it is a mistake to exclude not only the inspiratory flow-volume loop but the tidal loops as well. We need every clue we can get.

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