Methods for Cardiopulmonary Exercise Testing

Kenneth C. Beck

Idelle M. Weisman

aPhysiological Imaging Laboratory, Department of Radiology, University of Iowa, Iowa City, Iowa;

bHuman Performance Laboratory, Department of Clinical Investigation, Pulmonary-Critical Care Service, William Beaumont Army Medical Center, El Paso, Tex., and Department of Medicine, Pulmonary-Critical Care Division, University of Texas Health Science Center at San Antonio, San Antonio, Tex., USA

Summary

Over the last 20 years, CPET has expanded to include a wide spectrum of clinical applications. This has challenged clini-cal exercise testing laboratories to provide flexible, yet stan-dardized methodological approaches relevant to clinical deci-sion-making. Standardization of important methodological practices/processes is necessary to optimize clinical application [1]. This chapter will review the practical aspects of setting up a clinical exercise-testing laboratory for the evaluation of both healthy subjets and patients and will utilize the most widely accepted/applied criteria, as standardization is an evolving pro-cess. The following topics will be included: equipment, method-ology for the determination of metabolic responses to exercise and for quantifying external work, protocols, monitoring, con-duct of the test, patient safety, and emerging methodology for the evaluation of ventilatory limitation.

Exercise Testing Equipment

Layout of a typical clinical exercise testing laboratory is shown in figure 1. During a cardiopulmonary exercise test (CPET), an external work load is imposed on the pa-tient while physiological monitoring documents changes in external work intensity, metabolic gas exchange,

oxy-The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of De-fense.

gen saturation of arterial blood using pulse oximetry (SpO₂), electrocardiograph (ECG), blood pressure, and possibly arterial blood gases or additional specialized tests such as spirometry and exercise tidal flow volume loops.

Measuring Exercise Intensity: Ergometry

Exercise uses the body’s internal energy stores to per-form useful external work. Work is equal to the force times the distance over which it acts; the rate of perfor-mance of the external work is defined as power. The unit of work is the joule (equal to 1 Newton^Wmeter) and power is measured in joules^Ws^–1or watts. Power output is also commonly expressed in kilopond meters per minute, where 100 W = 612 kp^Wm^Wmin^–1[2]. The external power output should be quantifiable by measuring force (on pedals, or on the tread), distance (crank length, tread length) and time.

The quantitative assessment of power output is made using either a cycle ergometer or a treadmill. With cycle ergometers, the power output is measured directly by measuring the resistance required to turn the pedals (tor-que, usually with an internal force transducer) and crank revolutions per minute (RPM). Power output is torque times RPM. With the treadmill, determining the precise power output is more difficult. External energy consumed while walking or running on a flat motorized treadmill is essentially zero, although clearly the metabolic energy requirement increases with walking speed. The metabolic requirement for walking is derived entirely from work

44 Beck/Weisman Fig. 1. Cardiopulmonary exercise testing (CPET) laboratory. Shown are a treadmill, electrically braked cycle ergometer (right) and a mechanically braked cycle ergometer (‘Monarch’, left). At rear is the collection of monitoring equipment including computer for acquisition of breath-by-breath metabol-ic data, and ECG machine. Photograph courtesy of the Human Performance Labora-tory, William Beaumont Army Medical Cen-ter, El Paso, Tex.

Table 1. Comparison of ergometers used in CPET

Cycle ergometer

Treadmill

V˙O₂max lower higher

Leg muscle fatigue often limits performance

less often limits performance Work rate quantification yes estimation only Blood gas collection easier more difficult Instrumentation noise

and artifacts less more

Safety safer less safe (?)

Weight bearing in obese less more

More appropriate for patients active normals

required to move the limbs, and from the up and down motion against gravity. When the treadmill is inclined, power output increases due to the work against gravity needed to prevent downward motion. Thus, power output is related to body weight in addition to treadmill speed and elevation [3, 4]. The treadmill can impose noise on instrumentation signals such as ECG, blood pressure, and gas exchange measurements. V˙_O₂max is often 5–10% low-er on the cycle as only the leg muscles are used during exercise; consequently, leg fatigue is often the limiting fac-tor to exercise performance. For quantitative assessment of exercise response in the clinical laboratory,

electroni-cally braked cycle ergometry is preferable to treadmill testing for several reasons summarized in table 1: direct quantitation of work rate, less noise (artifact) on ECG, easier to collect blood samples during exercise, less expen-sive, and safer across a wide spectrum of clinical patient populations.

Metabolic and Ventilatory Responses

There are four basic measurements that are essential in quantitating the response to exercise: Oxygen consump-tion (V˙_O₂), carbon dioxide production (V˙_CO₂), heart rate (HR), and expired minute ventilation (V˙_E). In turn, an impressive number of derived variables can be measured during CPET; their impact on the interpretative process and clinical decision-making has been noted previously [5–7] and reviewed in the chapter on Interpretation. His-torically V˙_O₂and V˙_CO₂measurements were made by timed collection of expired gas into large collection bags [8].

Today, the two most common methods for providing rap-id on-line analysis are the mixing chamber technique [6, 9] and breath-by-breath technique [10], both of which require continuous measurement of expiratory flow (or occasionally volume) and continuous gas concentration.

Expiratory Flow and Volume Measurement. Most equipment measures instantaneous flow using a pneumo-tachograph and integrates that signal to obtain volume.

Pneumotachographs operate on a number of different principles, the most common of which are listed in table 2. Note that each type exploits different properties

Screen-type

Exercise Testing Methodology 45

Table 2. Methods for continuous measurement of flow and volume (types of pneumotachographs)

Principle of operation Advantages Disadvantages

Differential pressure across screen element

Proportional to gas density and viscosity

Linear response Seriously affected by moisture or

sputum impaction Not disposable

Bernoulli or Pitot tube

Differential pressure within gas stream

Proportional to gas density

Not seriously affected by moisture or sputum Lightweight

Disposable

Highly nonlinear response requires computerized compensation

Hot wire anemometer

Current maintains temperature of resistance wires

Exploits heat capacity of gas

Not seriously affected by mosture buildup Linear response

May be affected by sputum impaction Not disposable

Turbine Registers volume, not flow Counts revolutions of lightweight spinning fan blade

Least sensitive to changes in gas species (may be affected slightly by gas density or viscosity change)

Not seriously affected by moisture

Constant calibration (one revolution = fixed volume)

May be affected by sputum impaction

‘Over spin’ due to intertia requires computerized compensation Not disposable

of the gas (density for screens and Pitot tubes, heat capaci-ty for the hot wire). If a study is being undertaken with an inspired gas other than room air (e.g. high O2, or He/O2

breathing), the manufacturer of the equipment must be consulted and validation should be performed.

The calibration curve of any pneumotachograph can be affected by its mounting location in the system because of entrance and exit effects of flowing gases. Thus, care must be taken to ensure proper attachment to the exercise equipment prior to daily calibration. A common means for daily calibration is with a 3L gas syringe. The calibra-tion procedure should include pumping the syringe at var-ious rates to confirm that output of the pneumotacho-graph is independent of flow over the range expected dur-ing exercise [11, 11A]. The internal resistance and dead space volume of the pneumotachograph and associated valves must be taken into consideration. Although good data regarding the effect of breathing resistance on exer-cise response are not available, a resistance of more than 1–2 cm H₂O^Wl^–1^Ws^–1will likely be sensed by subjects at high levels of exercise. Added dead space of equipment will manifest itself as an increase in ventilatory require-ment, particularly at rest and lower levels of exercise.

Gas Concentration. Measurement of V˙_O₂ and V˙_CO₂ requires determination of concentrations of O₂and CO₂ in the expired and inspired air in addition to flow or vol-ume. If the classic bag collection technique is being used, the time taken to analyze the gas is not a critical issue, and chemical gas absorption methods are often used (Haldane

and Scholander techniques). Real time data analysis re-quires more rapid analyzers. Essential requirements for a gas analyzer include speed of response, linearity, stability of calibration, and independence of output (i.e. presence of CO₂does not affect O₂measurement). Validation of these properties can be accomplished with a set of 3–4 precision grade gas tanks. Testing at least one of these gases both dry and humidified will identify how the ana-lyzer is affected by water vapor.

Basic Concepts of Metabolic Measurements

Bag collection, mixing chamber, and breath-by-breath methods all use the same set of basic equations to calcu-late V˙_O₂and V˙_CO₂. These equations express the mass bal-ance of O₂and CO₂by quantifying the amount of the gas taken in during inspiration less the amount given off dur-ing expiration. The followdur-ing basic equations are used [2, 6]:

V˙O₂= V˙I WFIO2 – V˙E WFEO2,

where over-dotted V’s indicate timed collections of gas volumes and the subscript E indicates mixed expired gas, as in a well mixed bag of expired gas. This equation has both inspired and expired gas volumes, but only one of these volumes needs to be measured, usually expired vol-ume:

V˙I(STPD) = V˙E(STPD)^WFEN2/FIN2 = V˙E(STPD)^W(1.0 – FEO2 – FECO2)/FIN2,

46 Beck/Weisman

where F_IN₂is inspired N₂concentration (0.79 for room air) and F_EN₂is the mixed expired N₂(in a bag).

The equation for V˙_CO₂is the reverse of the one for V˙_O₂ (expired CO2 volume minus inspired CO2 volume), but the CO₂concentration is near zero in room air, so the inspired volume is often omitted:

V˙CO2 = V˙E WFECO2 – V˙I WFICO2, but since FICO2 " 0, V˙CO2 = V˙E WFECO2

The metabolic measurements V˙_O₂and V˙_CO₂are ex-pressed in standard temperature and pressure conditions (STPD). The conversion from ATPS (ambient tempera-ture and pressure, saturated), to STPD is performed using:

ATPS to STPD = Pbar – PH2O(t) 760

273 273 + t,

where P_baris barometric pressure (mm Hg), t is room tem-perature in°C and P_H₂_O(t) is determined from lookup tables of water vapor pressure against temperature.

The minute ventilation of the lungs is usually reported in body temperature pressure saturated conditions. The conversion from SPTD to BTPS is straightforward, since it involves three numbers that do not vary:

STPD to BTPS = 760 Pbar – PH2O(37° C)^W

310 273= 863

Pbar – 47

Example: In a laboratory at about 700 feet altitude above sea level (P_bar= 740 mm Hg) and typical room tem-perature of 22°C, a one minute collection of expired gas, or measurements obtained from a mixing chamber sys-tem, might be as follows: V˙_E= 50 liters/min, F_EO₂= 16.7%, F_ECO₂= 4.0%.

E The V˙_Ein STPD conditions is found from the conver-sion of ATPS to STPD: (740 – 20)/760 ! 273/295 = 0.8767, so V˙_E(STPD) is 43.84 liters.

E The inspired volume is obtained from 43.84 ! (1.0 – 0.167 – 0 .04)/0.79 = 43.98 liters/min.

E V˙_CO

2 = 43.84 ! 0.040 = 1.75 liters/min.

E V˙_O

2 = 43.98 ! 0.2095 – 43.84 ! 0.167 = 1.89 liters/

min.

E Reported V˙_E(BTPS) = 43.84 ! 863/(740 – 47) = 54.6 liters/min.

Effects of Water Vapor. Expired gas is warmed and humidified compared to inspired gas. Water vapor repre-sents about the same fractional concentration as CO₂in expired air, but is a much lower concentration in inspired air of most laboratory environments. Water vapor is nev-er measured directly, and rapid gas analyznev-ers used in most commercial systems (with the exception of the few that rely on mass spectrometry) require the gas sample to be

dried before analysis because the analyzers are either damaged or their output affected by water vapor. It is common for manufacturers to use drying gas sample lines, in which water vapor is absorbed in transport from the mouth to the gas analyzers. Drying sample lines are prone to failure, and this failure to correct adequately for water vapor in the expired gas can be a surprisingly large (20–

25%) source of error in either breath-by-breath or mixing chamber systems [12].

Breath-by-Breath and Effects of Gas Analyzer Time Delay. The breath-by-breath method samples gas flow and concentration over the breath to obtain inspired and expired volumes of CO₂and O₂per breath. These quanti-ties are then used in mass balance equations combined with breath timing information to determine V˙_O₂and V˙_CO

2 extrapolated to 1 min. A technical hurdle is the fact that flow measurement occurs nearly instantaneously, but gas concentration signals are delayed by the transit time of the gas along the sampling tubing into the instrument.

When performing breath by breath integration, it is im-portant to temporally realign the gas concentration and flow signals [13, 14]. Most automated commercial sys-tems have computer software that accomplishes this re-alignment with a built-in calibration routine that deter-mines the delay time that is used.

Mixing Chamber. The mixing chamber technique di-rects expiratory gas into a 5- to 10-liter chamber with internal baffles to facilitate mixing. Mixed gas concentra-tion and expiratory flow are measured continuously near the outlet of the box. In addition to the delay time for gas concentration measurement mentioned above, the gas concentration signal of a mixing chamber system is de-layed relative to the flow signal by the time to transport exhaled gas from the breathing valve to the mixing cham-ber. Because of changing V˙_Eduring exercise, the latter delay is not a fixed time period, but is determined from the ratio of (tubing volume + box volume)/V˙E. Computer-ized systems can make real time adjustments for this varying delay.

Comparing Metabolic Measurement Techniques Of the three methods for assessing V˙_O₂, V˙_CO₂and V˙_E, the breath-by-breath technique has become the most com-mon, although there are still many mixing chamber sys-tems in use (table 3). Both are acceptable for clinical exer-cise testing. Direct bag collection is usually reserved for validation studies. The breath-by-breath method requires a digital computer to carry out the calculations in real time but has the advantages of flexibility and high time resolution for changes in metabolic rate or ventilation.

Accuracy

Exercise Testing Methodology 47

Table 3. Comparison of techniques for measuring V˙_O

2, V˙CO₂and V˙E

Feature Breath-by breath Mixing chamber Bag collections

variable, depends on calibration of flow meter, gas analyzer and handling of water vapor

high for steady state conditions

Laboratory space low, needs computer, compact gas analyzers, calibration tanks

low, needs computer or strip chart recorder, compact gas analyzers, calibration tanks

high, needs means to collect gas volumes in large bags, measurement of large gas volumes (Tissot spirometer) and high precision gas analysis equipment Patient interface lightweight pneumotachograph and gas

sampling lines allow freedom of movement

requires expired gas tubing to mixing chamber, restricting movement

requires expired gas tubing to expired bag, restricting movement

Technical ease of use

equipment is usually portable, and requires daily calibration

equipment is usually portable, requires daily calibration

requires setup of bulky equipment; gas analysis methods (Haldane, Scholander) are usually laborious

Time resolution may be breath-by breath variable, may be 30–60 s at low ventilation rates, but nearly breath-by-breath at high ventilations

usually 60 s bag collection, can do 30 s collections at high intensities

Immediacy of results

computerized real time computations and displays

data are usually calculated after exercise testing

However, there is also a high degree of breath-to-breath variability in the data. Some of the breath-to-breath vari-ability is caused by variations in mismatch between inspired and expired volume of each breath, leading to variation in gas stores in the lung [14, 15]. For practical purposes, most laboratories use averaging techniques to smooth the noise. There are two broad choices for averag-ing methods: average over time or average over fixed number of breaths. For both, the longer the averaging interval and the more breaths in the average, the more the data are smoothed [16–18]. However, there is a trade-off:

as data are smoothed, rapid changes may be obscured. As peak V˙_O₂usually occurs during a period of non-steady state metabolic response, it could be underestimated.

When averaging by fixed number of breaths, the time interval of the average decreases as breathing rate in-creases late in exercise. A 20- to 30-second moving aver-age is probably a good choice for routine testing, though up to 60 s averaging may be appropriate to mimic tradi-tional bag collections [2]. Additradi-tional studies are required to determine the clinical significance of these different interval-averaging techniques.

The V˙_O₂and V˙_CO₂data coming from mixing chamber systems are smoother than unaveraged breath-by-breath data simply because the mixing chamber provides a phys-ical averaging mechanism. In addition to the inability to measure P_ETO₂and P_ETO₂, the only real disadvantage of mixing chamber systems over breath-by-breath systems is the lack of time resolution. However, modern mixing

chamber systems have improved time resolution, while true breath-by-breath time resolution is generally not nec-essary in clinical testing situations.

Quality Control and Validation of Equipment The equipment manufacturer should provide data sheets indicating results of validation testing. It is the responsibility of the laboratory to insure continuous accu-racy over time as the equipment ages. Periodic quality control (QC) testing often makes the assumption that either the ergometer or the metabolic measuring equip-ment is operating properly. For instance, it is common to validate metabolic measurement systems by having a nor-mal subject exercise at a given intensity while measuring their V˙_O₂, V˙_CO₂, and V˙_Eand comparing the values ob-tained with those expected at the work intensity setting [3, 6, 11A]. If the ergometer is not properly calibrated, an

‘error’ would be detected in metabolic data.

Reproducibility of Measurements

As with all laboratory measurements, there is some inherent ‘noise’ or uncertainty in the measurement of responses to exercise. Consideration of the uncertainty of CPET variables is important because of its impact on the interpretation of CPET results. Numerous studies have shown the test-retest variability of both metabolic mea-surements (V˙O₂, V˙CO₂, and V˙E) and external work

intensi-20

48 Beck/Weisman

Table 4. Reproducibility of maximal exercise capacity in normals and selected patient populations

Ref.

No.

Sample size

* VO₂max * VEmax AT Maximal

power

Disease

6 8.4% 4.4% 12.1% 5.5% normal

88 10 5.0% 7.0% 13.0% 7.0% normal

89 11 3.0% 5.0% – 3.7% COPD

90 20 9.0% 8.1% – 9.7% COPD

91 13 6.6% 6.3% – 13.8% COPD

19 6 5.3% 5.5% – 5.6% ILD

92 11 4.1% 6.3% – 3.6% CHF

* Table adapted from Marciniuk et al. [19]. Table entries are coefficient of variation (SD/

mean) of the indicated variable. AT = The V˙O2 at the anaerobic threshold; COPD = chronic obstructive pulmonary disease; ILD = interstitial lung disease; CHF = chronic heart failure.

ties is quite low in both normal and patient populations when individuals are retested in the same laboratory [19]

(table 4). Because exercise testing is strongly dependent on patient motivation, which in turn can be affected by motivational skills of testing personnel, there may be some variability within a laboratory among testing per-sonnel. In addition, variability between laboratories is affected by adequacy of equipment calibration and main-tenance. The variability among testing personnel and among laboratories has not been extensively studied.

Finally, time of day [20] and laboratory environment (temperature, humidity) may affect test results. To achieve good comparable data for comparison purposes,

In document Clinical Exercise Testing (Page 53-66)