Key Points

Spirometry is the most commonly performed and standardized measurement of pulmonary function; it measures the volume and ow rate of air that leaves the lungs (how much and how fast).

Two separate methodologies are used to quantitate RV, FRC, and TLC: body plethysmography and gas dilution.

Other pulmonary function tests include maximal voluntary ventila-tion, maximal respiratory pressures, and lung compliance.

Cardiopulmonary exercise testing not only delineates the reserve of each of the contributing subcomponents of the process of res-piration but also allows us to integrate the effects of a myriad of measurable and unmeasurable system subcomponents to assess functional status through measurements of maximal power output and oxygen consumption.

compliance, resistance, respiratory pressures, airway hyper-reactivity, or bronchodilator reversibility) and those that focus on gas exchange: arterial oxygen and carbon dioxide partial pressures (PaO2 and PaCO2) and saturations (SaO2 and SaCO2), alveolar-arterial oxygen pressure difference (P[A a]O2), diffusing capacity (DLCO), and physiologic dead space ventilation (V

.D/V

.T). Various lung diseases, or individ-

ual variation within a given disease, may result in discordant impairment between various mechanical properties or between mechanical and gas exchange properties. Thus, a combination of tests to evaluate lung mechanics and gas exchange will provide the most comprehensive understanding.

SPIROMETRYSpirometry is the most commonly performed and standard-ized measurement of pulmonary function. This test measures the volume and ow rate of air that leaves the lungs (how much and how fast).

Traditionally, exhaled volume is measured as a function of time using a volume-displacement spirometer with ow rates calculated by dividing volume into timed segments. It is now more common for systems to primarily measure ow, with real-time integration of ow over time to obtain volume, owing to the development of less expensive and more compact and accurate ow-sensing devices and fast microprocessors. The total volume exhaled from a full inspiration (total lung capacity [TLC]) to a full expiration (residual volume [RV]) is termed the vital capacity (VC). The maneuver can be performed using a forced complete exhalation, referred to as forced vital capacity (FVC), or during a slow complete exha-lation, de ned as slow vital capacity (SVC). Forced exhala-tion is necessary to assess expiratory ow rates, including peak expiratory ow (PEF) and the volume exhaled in the rst second (FEV1) as well as other less commonly used timed volumes (e.g., FEV0.5, FEV3.0 [volumes exhaled in the rst half second and the rst 3 seconds, respectively]) and forced expiratory ows (FEF50%, FEF25-75% [forced expiratory ow at 50% of the FVC, and forced expiratory ow between 25% and 75% of the FVC, respectively]). The parameter FEV1 is the most reproducible and validated measure derived from the forced expiratory maneuver and, with its ratio FEV1/FVC, provides the foundation for lung disease classi -cation, discussed later (Fig. 3-1).

Slow vital capacity maneuvers are used to assess other static lung volumes and capacities such as inspiratory capacity (IC) and expiratory reserve volume (ERV) and, because spi-rometry cannot measure the air remaining in the lung after a complete exhalation, are often linked to tests of lung volume (Fig. 3-2).

19

PULMONARY PHYSIOLOGIC TESTINGchapter

3 Frank C. SciurbaSteve H. Salzman

The physiologic role of the lung is to maintain homeostasis of the arterial pH, PCO2, and PO2 under varying conditions of oxygen consumption and carbon dioxide production, a goal that is dependent on the lungs properties both as a mechani-cal structure and as a gas-exchanging surface. Clinical pulmo-nary function tests (PFTs) provide practical assessment of the integrity of the components of the respiratory system. Such testing provides a key ingredient in the diagnosis and assess-ment of severity of lung disease and is critical in the determination of perioperative risk. Cardiopulmonary exer-cise testing (CPET) may offer further diagnostic and prog-nostic advantages over resting assessment of the respiratory system because it measures physiologic reserve and inte-grated functional capacity that can only be inferred from resting measurements. It is imperative that the thoracic surgeon be competent not only in the application of lung function indices but also in the assessment of the techniques and quality of the data provided. In this chapter we offer a practical approach to the assessment of lung function and exercise physiology.

INDICATIONS FOR PULMONARY FUNCTION TESTINGPulmonary function tests (PFTs) have a central role in the evaluation of the thoracic surgery patient. The role of these tests in preoperative risk assessment is discussed in Chapter 2. Other indications are highlighted in Table 3-1.

PFTs, although essential to the proper assessment of the respiratory system, rarely provide a speci c diagnosis in the absence of complementary clinical and radiographic data. Tests of lung function can be broadly separated into those that evaluate the mechanical properties (volumes, ows,

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Section 1 Introduction20

Technique and Speci c MethodologyThe forced maneuver consists of three distinct phases (Miller et al, 2005)1:

1. Maximal inspiration2. A blast of exhalation3. Continued complete exhalation to the end of test (until

no more air can be exhaled but maintaining an upright posture)

It is then followed by a rapid inhalation back to full inspira-tion. This effort can be shown graphically as a ow-volume loop (FVL) or volume-time curve (V-t curve), both repre-senting the same FVC maneuver (see Fig. 3-1). Enthusiastic coaching by the technician, including appropriate body lan-guage and phrases, is necessary to get full effort from the patient. The technician rst explains and demonstrates the technique, instructs the patient to inhale rapidly and com-pletely with minimal pause at full inspiration (only 1-2 s), then instructs the subject to blast the air from the lung and keep going, keep going, keep going until the patient has fully exhaled. An unacceptable pause (e.g., 4-6 s) at TLC, delaying the start of exhalation, has been shown to be associ-ated with reductions in FEV1 and peak expiratory ow (PEF).

Flow

(L/s)

FVC

FEF50

FEV1

FEV1

FIF50

Volu

me

(L)

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0.0

8.0

6.0

4.0

2.0

0.0

2.0

4.0

6.0

8.0

TLC

TLC FVC

FEF 2575%

RV

RV

0.0 1.0 2.0Time (sec)

3.0 4.07.0 6.0 5.0 2.0Volume (L)

3.0 1.02.0BA

FIGURE 3-1 Flow and time curves. A, Good duration of effort is seen on the volume-time curve by the plateau of volume change over time. In a normal ow-volume loop, good early effort is shown by the rapid upstroke to a slightly rounded sharp peak ow. Good duration of effort is illustrated by the upward concavity at the end of exhalation, indicating slowing of air ow near residual volume. Patients with obstructive lung disease have deeper, upward concavity throughout exhalation on the ow-volume loop. FEF50, forced expiratory ow at 50% of the forced vital capacity (FVC); FEV1, volume exhaled in the rst second; FIF50, forced inspiratory ow at 50% of FVC; RV, reserve volume; TLC, total lung capacity.

IC IRV

Lung volumes and capacities

IC

FRC

TV

SVC

RV RVRV

ERV ERV

TLC

FIGURE 3-2 Subvolumes. ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; SVC, slow vital capacity; TLC, total lung capacity; TV, tidal volume.

TABLE 3-1 Common Indications for Pulmonary Function Testing

Categorization of the type and severity of physiologic perturbation Restrictive versus obstructive categorization Asthma versus emphysema

Objective assessment of pulmonary symptoms Documentation of abnormality Disability assessment

Documentation of progression of disease Chronic obstructive pulmonary disease Neuromuscular disease

Documentation of the patients response to therapy Asthma control Lung volume reduction surgery Sarcoidosis

Preoperative assessment Lung cancer resection operability Nonthoracic surgery Timing of lung transplantation

Screening for subclinical disease Emphysema (in a tobacco smoker) Occupational risk Diseases associated with pulmonary abnormalities

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Chapter 3 Pulmonary Physiologic Testing 21

Patients can be standing or sitting during the test, and this is recorded on the report. Sitting is generally preferred over standing for safety reasons because equivalent results are obtained in normal-weight individuals for either position. Obese subjects will frequently obtain a deeper inspiration in the standing position, resulting in higher expiratory volumes and ows (Miller et al, 2005b).2 It is important to use the same position for longitudinal studies.

Acceptability and Repeatability CriteriaClinicians using parameters derived from these maneuvers need to become familiar with acceptable quality control stan-dards, particularly when one is faced with deciding whether to utilize results provided from unfamiliar laboratories. Examination of numerical data as well as the expiratory ow and volume curves is important to determine when an indi-vidual FVC measurement or trial has met the American Thoracic Society (ATS) and European Respiratory Societys (ERS) acceptability criteria for adequate effort (Table 3-2) (Miller et al, 2005a).1 Large variability among maneuvers can be due to incomplete inhalation before the expiratory blow or submaximal or variable expiratory force and duration. In general, acceptable inspiratory and expiratory efforts are also reproducible. Ideally, both the FVL and V-t curve are reviewed when assessing test quality. The FVL graphs ow versus volume, resulting in relative expansion of the graphic data for the rst second, whereas the V-t curve gives equal spacing for each second and allows better resolution of the events marking the end of the test. Coughing or glottic closure is more easily recognized on the FVL because the rapid tran-sients of ow result in large up and down spikes in the curve (Fig. 3-3). Submaximal effort is recognized graphically on the FVL by a slow rise to the peak ow or by a rounding and broadening of the normal shape at the peak ow. Submaximal early effort, resulting in a slow upswing in the V-t curve, is

TABLE 3-2 2005 American Thoracic SocietyEuropean Respiratory Society Acceptability Criteria for Spirometry*

Within ManeuverSmooth continuous curve (free from artifacts, e.g., cough in the

rst second, early termination or cutoff, effort that is not maximal throughout, leak)

Good start of test (blast it out) Extrapolated volume 10 years 3 seconds in subjects 15 seconds will rarely change clinical

decisions or Subject cannot or should not continue further exhalation

Between ManeuverAfter three acceptable maneuvers, if the largest and second largest

FEV1 and FVC values are within 150 mL of each other, the session is completed

If not, continue spirometry until criteria are met; or a total of eight trials have been done; or the patient cannot or should not continue testing

Final report FEV1 and FVC reported as the largest values from any

acceptable trial Best test curve from trial with largest sum of FVC + FEV1 Other ow parameters from best test curve

FEV1, volume exhaled in the rst second; FVC, forced vital capacity.*Modi ed from Miller MR, Hankinson J, Brusasco V, et al: Standardi-sation of spirometry. Eur Respir J 26:319-338, 2005.

10.0

8.0

6.0

4.0

4.0

0.0

2.0

4.0

0.0

0.0 1.0 2.0Acceptable loop Inadequate loop

3.0 4.04.0

Good start

Rapid rise(blast)

Smoothinhalation

Continuouscurve

Gradual returnto 0 flow

Sharp peak

Plateau

Hesitantstart Slow rise

Incompleteinhalation

Abrupt endflow

Artifacts(glottic closure)

FIGURE 3-3 Characteristics of an acceptable and technically inadequate ow-volume loop.

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Section 1 Introduction22

expressed quantitatively as extrapolated volume and often printed in the numerical section of the report.

The ATS-ERS criteria for spirometry apply within-maneuver acceptability criteria to individual FVC efforts (see Table 3-2). The spirometry standards have been met when three acceptable FVC efforts have been obtained, with the best and second best meeting between-maneuver acceptabil-ity criteria, also referred to as repeatiblilty (Miller et al, 2005a).1 The difference between the largest and second largest FEV1 or FVC ideally is less than or equal to 150 mL, and in patients with an FVC less than 1.0 L it is less than or equal to 100 mL. With the exceptions of maneuvers that contain a cough or glottic closure in the rst second or excessive volume of extrapolation, the use of data from maneuvers with poor repeatability or that fail to meet end-of-test criteria is left to the discretion of the interpreter (Miller et al, 2005a).1

Final Report DataThe report comments on the test quality, referring to the test components that were not reliable. A suboptimal test can be reported at the discretion of the interpreting physician in an appropriate clinical context as long as the report is speci c in describing the likely direction and magnitude of errors (Miller et al, 2005a).1-3 For example, the FEV1 may be useful and can be reported from maneuvers with early termination of exhalation, as long as there is an acceptable start of exhala-tion and no cough in the rst second (usable curves), although the con dence in these data would be lower than a better performed FVC that met all acceptability criteria (Miller et al, 2005a).1

The FEV1 and FVC that are reported are the largest values from any acceptable trial, not necessarily from the same maneuver. The best test curve comes from the trial with the largest sum of FVC + FEV1. Other ow parameters come from this same curve.

LUNG VOLUME MEASUREMENTSAs discussed earlier, spirometry only measures the air exiting the lungs and thus does not allow assessment of air remaining after a full expiration, which is necessary to calculate residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC). Two separate methodologies used to quantitate these volumesbody plethysmography and gas dilutionare discussed.

De nitionsThe 2005 ATS-ERS standards on lung volumes employed the following de nitions.4 A lung volume parameter is termed a volume if it cannot be broken down into smaller subcompo-nents (see Fig. 3-2):

Tidal volume (VT or TV) is the volume of gas inhaled or exhaled during the respiratory cycle.

Inspiratory reserve volume (IRV) is the maximum volume of gas that can be inhaled from the end-inspiratory level during tidal breathing.

Residual volume (RV) refers to the volume of gas remaining in the lung after maximal exhalation (regardless of the lung volume at which exhalation was started).

Expiratory reserve volume (ERV) is the volume of gas that can be maximally exhaled from the end-expiratory level during tidal breathing (i.e., from the FRC).

Lung volumes that are made up of the addition of multiple lung volumes are termed capacities:

Functional residual capacity (FRC) is the volume of gas present in the lung at end-expiration during tidal breathing; thus, FRC = RV + ERV.

Inspiratory capacity (IC) is the maximum volume of gas that can be inspired from FRC; thus, IC = VT + IRV.

Vital capacity (VC) is the volume change at the mouth between the positions of full inspiration and complete expiration. It can be measured in one of three ways:

VC = ERV + IC or VC = IRV + VT + ERV or VC = TLC RVTotal lung capacity (TLC) refers to the volume of gas in

the lungs after maximal inspiration or the sum of all volume compartments:

TLC = RV + ERV + VT + IRV or TLC = VC + RV or TLC = FRC + IC.

Thoracic gas volume (TGV or VTG), a term that still appears on many pulmonary function reports, is the absolute volume of gas in the thorax at any point and a term often used in body plethysmography when measuring FRC. It is too nonspeci c and is replaced with more speci c terminol-ogy, such as FRC by body plethysmography or TGV at FRC (FRCpleth).

Body PlethysmographyPlethysmographic techniques have become the gold standard for measurement of lung volumes. The patient sits in a large, air-tight, glass-enclosed box and breathes through a mouth-piece (Fig. 3-4). During the test an electronic shutter tem-porarily occludes the mouthpiece and the patient continues to pant against the closed shutter. FRC is chosen as the starting point because the chest wall is in a relaxed state and it thus tends to be a very reproducible value. During an inspiratory pant against the closed airway the chest expands slightly, creating a negative pressure swing at the alveolus that can be measured at the mouth. Plethysmographic technique assumes that mouth and alveolar pressures are equal, whereas there is no ow as the subject pants against a closed shutter. The test employs Boyles law, which states that the product of the pressure and the volume of a gas at a given temperature remains constant (P1 V1 = P2 V2). If the pant begins as the shutter is closed at FRC, then (Patm FRC) = (Patm + Pmouth) (FRC + V) where Pmouth is the pressure swing at the mouth and V is the volume change of the thorax. V is determined by applying Boyles law for a second time whereby the pressure change in the air-tight box Pbox is proportionate to the V of the chest wall. Intuitively, an individual with a small amount of air left in the lungs at end-expiration (small FRC) will have a higher mouth pressure change, when panting against a closed shutter, for a given change in thoracic volume (re ected in Pbox).

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Chapter 3 Pulmonary Physiologic Testing 23

In contrast, an individual with a large FRC will have a smaller mouth pressure change than a patient with a low FRC for a similar change in thoracic volume or Pbox. Pitfalls in the measurement of lung volumes and its subcomponents related to improperly timed shutter closure are demonstrated in Figure 3-5.

Gas DilutionThe helium dilution technique is a closed-circuit technique. A spirometer is lled with a mixture of helium and oxygen. The amount of helium in the spirometer (helium concentra-tion (C1) volume of spirometer [V1]) is known at the begin-ning of the test. As the patient exhales to FRC, a valve switches the patient into a closed circuit breathing from the spirometer. Because the breathing circuit is closed (assuming no leaks) the total volume of helium in the system remains constant during the test. By measurement of the nal helium concentration in the circuit after the patient has equilibrated with the mixture (C2), FRC can be solved from the equation: (C1 V1 = C2 (V1 + FRC)). Nitrogen washout technique involves collection of exhaled gas as the lung is washed out with a 100% oxygen mixture. The total volume of nitrogen collected after complete washout is then in proportion to the FRC.

Technique and Speci c MethodologyIn normal subjects, the same values for FRC and TLC will be obtained whether measured by gas dilution (He dilution or N2 wash-out), plethysmography, or planimetry (geomet-ric) measurement from a chest posteroanterior and lateral radiograph. On the other hand, gas dilution and wash-out techniques will underestimate FRC (and therefore RV and TLC) in patients who have severe inequality of the distribu-tion of ventilation, such as those with severe airways disease. Regions of lung with long-time constants (directly propor-tional to resistance and compliance) will equilibrate much more slowly than the length of a typical gas dilution test and so will not be seen by these techniques. Conversely, ple-thysmographic techniques measure all intrathoracic gas, whether it communicates with the airways or not. Bullae are an extreme example of this poorly communicating lung. This difference between plethysmographic and gas dilution mea-surements of lung volume may have independent clinical meaning as trapped gas and has been shown to decrease after lung volume reduction surgery.

Recent data indicate that FRC (and therefore RV and TLC) can be inaccurately overmeasured using plethysmo-graphic techniques in patients with severe air ow limitation. In these cases, severe air ow obstruction may result in phase

Electricallycontrolled shutter,closed atend-expiration

Mouth pressure (Pm)Change in mouth pressure (Pm)reflects change in alveolar pressure

Body Plethysmograph Methodfor Determination of FRC

Box pressure (Pm)Change in box pressure (Pm)reflects change in lung volume

Patient makespanting effortsagainst closedshutter

+

+FRC

FIGURE 3-4 Body plethysmography.

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Section 1 Introduction24

lag between alveolar and mouth pressures, resulting in slow to-and-fro ow during panting, such that mouth pressure lags behind alveolar pressure, resulting in a falsely high measure-ment of FRCpleth. Fortunately, this small error is in the direction that enhances the ability to recognize the underlying disease (i.e., the degree of hyperin ation is exaggerated).

As discussed earlier, plethysmographic measurements are combined with measurements derived from a VC maneuver, from which IC and ERV are also measured. Combinations of the data from these two separate measurements are used to obtain the other lung volumes (see Fig. 3-2). The 2005 ATS-ERS standards have recommended that the preferred testing sequence is a linked measurement (patient remains on the mouthpiece in the box throughout the sequence) of FRC followed by ERV, followed by IVC.4 With this approach, FRC is reported as the mean of technically satisfactory mea-surements linked to the technically satisfactory ERV and IVC maneuvers used for calculating the RV and TLC. The reported value for RV is the reported FRC minus the mean of the technically acceptable ERV measurements, linked to techni-cally acceptable FRC measurements. The reported TLC is the reported value for RV plus the largest of the technically acceptable IVCs. A second recommended method, although not the preferred approach, utilizes a separate IC maneuver immediately after the FRC measurement to measure TLC. This approach may be easier for some dyspneic patients. The TLC is determined as the mean of the three largest sums of technically acceptable FRC values and linked IC maneuvers. RV may be calculated as the mean TLC minus the largest VC measured.

Diffusing CapacityThe single-breath DLCO measures the capacity of the lung to transfer gas, using the test gas carbon monoxide (CO). Known as the transfer factor (TLCO) in Europe, it is measured in

milliliters per minute per millimeter of mercury (mL/min/mm Hg), thus it can be thought of as the ow rate (mL/min) of CO gas per millimeter of mercury of CO pressure gradient from alveolus to capillary blood.

CO is so avidly bound to hemoglobin that, unlike oxygen, little back-pressure develops in the capillary to slow its trans-fer from alveolus to blood as a given volume of capillary blood makes its transit through the capillary bed. CO is diffusion limited rather than perfusion limited and is thus ideal for assessing the lungs capacity to transfer gas. Consequently, its transfer is not dependent on cardiac output. It is dependent on the volume of the capillary bed exposed to alveolar surface and to the hemoglobin concentration because each increases the available mass of hemoglobin available for CO binding. The transfer of CO also depends on the properties of the alveolar-capillary interstitium (surface area and thickness). In addition, because little back-pressure of CO develops in the capillaries as a result of its transfer, the driving pressure for CO transfer can be measured from alveolar CO concentra-tion alone without the measurement of blood CO (except in the tobacco user).

Technique and Speci c MethodologyThe widely accepted technique used to measure DLCO, uti-lized in virtually all clinical laboratories, is the single-breath methodology, whereas historically, and still in research set-tings, other steady-state techniques are utilized. In the single-breath method, the subject exhales to RV and then rapidly inhales a gas mixture containing a minute concentration of CO (commonly 0.3%) and an inert tracer gas (usually 10% helium or 0.3% methane), which is used to adjust for dilu-tional effects. After a 10-second breath-hold at TLC, the patient rapidly exhales and, after a 0.75- to 1.0-L discarded sample (to exclude dead space collection), the exhaled gas (re ecting an alveolar sample) is collected and analyzed. Mea-surement of the initial (inspired) and nal concentration

TLC

TrueFRC

RV

O

BODY PLETHYSMOGRAPHY TECHNIQUE

False high FRCby amount a

a

Shutter closure

Mid-rest position

IC

ERV

FIGURE 3-5 Body plethysmography technique: box error. Linked FRC and SVC maneuver performed suboptimally. The SVC portion was well performed as demonstrated by the slowing of ow near full lung in ation and near full exhalation demonstrating full inspiratory effort and full expiratory effort. The quiet tidal breathing portion (left side of curve) did not settle down a stable end-expiratory baseline for establishing FRC. When the shutter closes in the body plethysmograph, the measurement of VLpleth (thoracic gas volume during body box) may be correct but the lack of a prior stable end-expiratory point to de ne FRC will also result in incorrect values for FRC, and also ERV and IC, which are referenced to the point of FRC. This will also result in incorrect values for TLC and RV, when derived from arithmetic use of FRC, IC, or ERV.

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Chapter 3 Pulmonary Physiologic Testing 25

(exhaled) of CO adjusted for gas dilution and breath-hold time determines DLCO.

Acceptability, Repeatability, and Number of TestsAcceptable maneuvers have an inspired volume (VI) greater than 85% of largest measured VC in less than 4 seconds; a breath-hold of 10 2 seconds without Valsalva or Mueller maneuvers; expiration in less than 4 seconds (and sample collection less than 3 seconds); and graphic evidence that dead space has been cleared and an accurate alveolar sample has been obtained.5 Repeatability is within 3 mL/min/mm Hg or within 10% of the highest value. The mean of at least two acceptable tests that meet this repeatability requirement is reported. No more than ve tests are performed because the resultant elevated carboxyhemoglobin (COHb) will affect the measurements.

Hemoglobin and Carboxyhemoglobin Adjustments of Measured DLCOBe wary of DLCO values that are reported without adjust-ment for hemoglobin. Patients with anemia have a lower measured DLCO, and patients with erythrocytosis have an elevated DLCO. Report the measured DLCO and adjusted or corrected DLCO, but base interpretation and trending on the adjusted values. The absolute adjustment, and the adjust-ment per gram per deciliter of hemoglobin deviation from normal (14.6 g/dL for men and 13.4 for women) increases with increasing anemia. When standard formulas are used, a hemoglobin concentration of 12 results in an 8% adjustment in the measured value; a hemoglobin of 10, an 18% adjust-ment; and a hemoglobin of 7, a 45% adjustment (ATS, 1995).5,6

Patients are instructed not to use tobacco before testing to minimize the effect of elevated capillary CO resulting in a lower measured DLCO. Although the ATS statement con-siders it optional, an acceptable adjustment of 1% of the measured DLCO per %COHb is appropriate. No adjustment is required for COHb under 2% because reference equations already account for this.5 It is not uncommon for a smoker who does not comply with instructions to abstain from tobacco use before testing to have a COHb of 5% to 10%.

Diffusing Capacity per Unit Lung VolumeIt is commonly incorrectly inferred that a normal DLCO per unit lung volume (DLCO/VA) rules out an intrinsic lung problem even when unadjusted DLCO is decreased. In patients with restrictive defects on PFTs and a low DLCO, a low DLCO/VA does, in fact, suggest parenchymal lung disease (e.g., interstitial lung disease, emphysema, or pulmonary vas-cular disease). In general, normal or high values for DLCO/VA occur in patients with an extrapulmonary cause of restriction, such as chest wall (obesity, kyphoscoliosis), pleural, or neu-romuscular diseases. On the other hand, a normal DLCO/VA does not rule out interstitial lung disease. It is more useful to think of the DLCO/VA as a ratio that discriminates the presence of matched defects in mechanics and gas exchange (normal DLCO/VA) from discordant defects resulting in dis-proportionately greater abnormality in gas exchange (low DLCO/VA).7

OTHER PULMONARY FUNCTION TESTS

Maximal Voluntary VentilationTo test maximal voluntary ventilation (MVV) the patient is instructed to breathe in and out as rapidly as possible for 12 seconds. The result is extrapolated to 1 minute and is expressed in liters per minute. Disadvantages of this test are that results depend on motivation, and it is tiring for patients. In the past the MVV was recommended to assess respiratory muscle weakness; however, in general it has no advantages over VC.

MVV remains a common tool used in assisting the inter-pretation of ventilatory reserve during CPET. In subjects who achieve a ventilatory limitation, such as patients with severe chronic obstructive pulmonary disease (COPD) or respira-tory muscle weakness, maximal exercise ventilation (VEmax) often approaches or exceeds MVV (VEmax/MVV > 0.75). MVV is commonly estimated from simple spirometric mea-sures (40 FEV1).

Maximal Respiratory PressuresThe most speci c tests to identify neuromuscular weakness as the cause of restriction are the maximal inspiratory pres-sure (MIP) and the maximal expiratory pressure (MEP). These parameters are also referred to as inspiratory pressure maximum (PImax) and expiratory pressure maximum (PEmax). The MIP assesses the lowest pressure a patient can sustain for 1 to 2 seconds when inhaling from an occluded mouthpiece connected to a manometer (Mueller maneuver). The most negative pressure is obtained when the test is performed at or near RV because the diaphragm is at its longest precontraction length, the optimal position for force generation. Conversely, the MEP is measured as an expira-tory effort (Valsalva maneuver) after inhaling to or near TLC.

Although simple tests, they are very effort dependent (patient and tester). A small leak is introduced to eliminate glottic and buccal occlusion and inadvertent measure of mouth pressures rather than intrathoracic pressures. Because of a learning curve, several trials are needed and careful instruction and encouragement are required. The reported value is the largest value that is reproducible and sustained for 1 second. The maximal value of three maneuvers that vary less than 20% is reported. Because they are very effort-dependent tests, the MIP and MEP are better at ruling out respiratory muscle weakness than making a diagnosis. A low result may be due to lack of full effort. The lower limit of normal for MIP measured at RV is 75 cm H2O in men and 50 cm H2O in women. The lower limit of normal for MEP measured at TLC is 100 cm H2O in men and 80 cm H2O in women. A normal MEP with a low MIP suggests isolated diaphragmatic weakness. MIP can be decreased in emphy-sema associated with lung hyperin ation and suboptimal respiratory muscle con gurations. In this setting the low inspiratory pressures are independent of intrinsic muscle weakness. As such, measurements of MIP have been shown to improve after lung volume reduction surgery in concert with improvements in resting lung hyperin ation.

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Section 1 Introduction26

Lung ComplianceAlthough not a routine test in most laboratories, a more direct way of distinguishing parenchymal lung disease from chest wall disorders as a cause of restriction or low DLCO is to measure lung compliance. These measurements require placement of esophageal (balloon) catheters to measure esophageal pressure, which re ects pleural pressure across a compliant esophagus. Patients are asked to relax against a closed shutter attached to a manometer that measures mouth pressure at various lung volumes. The difference between mouth and esophageal pressure represents the elastic recoil pressure of the lung, abbreviated PEL(L). Figure 3-6 repre-sents typical volume-pressure curves in diseases associated with decreased compliance (V/P), such as pulmonary brosis (right shift), normal compliance as is also present in chest wall abnormalities, and increased compliance such as with emphysema (left shift). PEL(L) at TLC, also represented as the ratio of PEL(L)/TLC and termed coef cient of retrac-tion, is a useful representative parameter derived during this testing. Interstitial lung disease will have a high PEL(L) at TLC and high PEL(L)/TLC, whereas chest wall restriction will present as a low PEL(L) but a normal PEL(L)/TLC. This low PEL(L) in chest wall restriction (e.g., due to pleural restriction, kyphoscoliosis, neuromuscular weakness) is due to underexpansion of a normal lung, held to low lung volumes by the extrapulmonary process. By contrast, the very low PEL(L) at TLC resulting in low PEL(L)/TLC seen in emphy-sema is a re ection of the intrinsic loss of elasticity. The normal range for PEL(L)/TLC is 2 to 8 cm H2O/L.

CARDIOPULMONARY EXERCISE TESTINGParameters traditionally considered to be the gold standards of cardiopulmonary function such as FEV1 and cardiac ejec-tion fraction often correlate poorly with symptoms or exer-cise capacity, and changes in these resting parameters after an intervention often do not re ect functional improve-

ments.8,9 Exercise testing not only delineates the reserve of each of the contributing subcomponents of the process of res-piration but also allows us to integrate the effects of myriad measurable and unmeasurable system subcomponents to assess functional status through measurements of maximal power output and oxygen consumption (ATS, 2003).10

Assessment of Maximal Exercise CapacityIn normal individuals and patients with cardiac abnormalities, exercise termination occurs at the maximal oxygen consump-tion (VO2max) due to overwhelming symptoms associated with metabolic demands at the limits of oxygen delivery and muscle oxidative capacity.

Oxygen consumption is commonly represented through the Fick equation:

VO2 = cardiac output (A V)O2 diff

Another way of representing this value allows better rec-ognition of the physiologic components that contribute to maximal oxygen delivery and oxygen extraction.

VO2max = heart rate(max) stroke volume(max) 1.34 Hgb SaO2 muscle extraction rate(max)

where (A V)O2 is the arteriovenous oxygen gradient, SaO2 is the arterial oxygen saturation, and Hgb is hemoblobin; max implies the parameter is at its maximal physiologic capacity.

The maximal values for each of these parameters depend on genetics, the level of conditioning, and the presence of disease. At rest, humans are capable of maintaining homeo-stasis under all but the most severe internal disease condi-tions or in the most extremes of physical environments, but abnormal reserves in any of the above physiologic attributes will commonly be exposed during exertion when the increased metabolic demands delineate the limits to the response. VO2max is reported as a percentage of predicted normal or adjusted simply for weight in milliliters per kilogram per minute.

Heart Rate Response to ExertionAlthough there is considerable variability in the heart rate response to exertion in normal individuals, heart rate nor-mally has a predictable slope relative to the increase in oxygen consumption (see Fig. 3-13A). At maximal exertion the normal heart rate response can be estimated simply as (220 age in years).

Ventilatory Response During ExerciseIncreases in minute ventilation (V

.E) during exertion are nec-

essary to maintain systemic blood gas and acid-base homeo-stasis. The formula describing the effect of changes in various factors on minute ventilation requirements is:

V.E = 0.86 VCO2/(PaCO2 [1 VD/VT])

The level of minute ventilation required will depend on the central set point for PaCO2, which is in uenced by central drive, vagal afferents, and humoral input (including pH and PaO2), the CO2 production, and the dead space proportion.

Normal

5

4

3

2

1

00 10 20

Volu

me

(L)

Distending pressure (cm H2O)30 40

Emphysema

Fibrosis

FIGURE 3-6 Static pressure-volume curves for patients with normal lungs, pulmonary brosis, and emphysema. Compliance represents the slope of the pressure-volume curve. (ADAPTED FROM MURRAY JF: THE NORMAL LUNG, 2ND ED. PHILADELPHIA, WB SAUNDERS, 1986, P 87.)

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Chapter 3 Pulmonary Physiologic Testing 27

Therefore, the rate of increase in V.

E is positively correlated with the level of exertional metabolism or carbon dioxide production (VCO2); inversely related to the arterial partial pressure of carbon dioxide central set point (PaCO2); and inversely associated with the proportion of tidal volume (VT) consisting of dead space (VD) identi ed as the ratio VD/VT. Lactic acidosis associated with increasing exertion in both normal and cardiac-impaired individuals can drive V

.E both

by increasing CO2 production associated with bicarbonate buffering and through direct effects on carotid body and central chemoreceptors.

VD/VT abnormalities are associated with most pulmonary parenchymal and vascular disease processes due to regions of excessive ventilation-perfusion ratio. Whereas absolute dead space rises normally during exertion, the VD/VT falls from 0.35 at rest to less than 0.20 at maximal exertion.

An arterial blood sample is necessary to accurately calcu-late the dead space proportion using the equation:

VD/VT = (PaCO2 PECO2)/PaCO2

where PECO2 represents the mixed expired CO2 concentration.

Maximal values of V.

E achieved during exertion are nor-mally less than 75% of a normal individuals ventilatory capacity or MVV (Fig. 3-7); thus, ventilatory capacity is almost never the cause of exercise limitation in a normal individual. The V

.E is commonly compared with the MVV to

assess the ventilatory reserve, expressing V.

E as a percentage of MVV. A V

.E/MVV of greater than 80% is supportive of

ventilatory mechanical limitations to exertion, in contrast to the usual oxygen delivery/utilization mechanism for exercise limitation described earlier in normal and cardiac patients.

Exercise Inspiratory Capacity and End-Expiratory Lung VolumeThe end-expiratory lung volume (EELV) in normal indi -viduals decreases with exertion, but COPD patients experi-ence dynamic hyperin ation during exertion due to an

inability to increase expiratory ow as expiratory time decreases and is characterized by increases in their EELV, resulting in further impingement on their IC (Fig. 3-8). This measure has been found to be a sensitive indicator of early disease, and dyspnea has been found to correlate closely with measurements of exercise EELV. The maneuver is based on the validated assumption that TLC, measured at rest, does not change during exertion. Multiple IC maneuvers can then be performed throughout exertion, and EELV is then calcu-lated as the difference between TLC and IC. Improvement in dynamic hyperin ation has been documented after bron-chodilator therapy and lung volume reduction surgery.

Impact of Exercise Protocol on OutcomeIt is important for laboratories performing exercise studies to understand the impact of variations in exercise protocol on exercise-derived indices. Incremental bicycle studies involve stepwise or ramped increases in workload (watts) until symptom limitation occurs. The protocol often involves a period of pedaling with no added workload followed by incrementation at a prede ned workload per minute. Treadmill studies can involve incrementation using any number of speed and grade combinations. Treadmill exercise protocols result in maximal oxygen consumption values approximately 10% higher than those achieved using cycle ergometry. Protocol durations that are too short or too long may affect maximal achieved values as well. Maximal exer-cise power output (watts) during incremental bicycle testing can vary dramatically with other seemingly subtle changes in exercise protocol. For example, the exercise protocol de ned by the National Emphysema Treatment Trial (NETT) to stratify patients into high and low exercise categories (cutoff 25 W for women and 40 W for men) in assessing candidacy for lung volume reduction surgery is very speci cally de ned as using 3 minutes of unloaded pedaling followed by a 5 W/min ramp if the resting MVV is less than 40 L/min and a 10 W/min ramp if MVV is greater than or equal to 40 L/min (NETT, 1999).11,12

COPD With Ventilatory Limitation

(MVV)

(MVV)

Normal

Work Rate or VCO2

VE

Work Rate or VCO2

VE

Ventilatoryreserve

VE = Minute ventilationMVV = Maximal voluntary ventilation

Alveolar ventilation Dead space

FIGURE 3-7 Ventilatory limit.

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Section 1 Introduction28

Safety IssuesStandard safety criteria for exercise termination that have been reported include the following13:

Chest pain suggestive of angina Evolving mental confusion or lack of coordination Evolving lightheadedness Electrocardiographic evidence of ischemia or serious

arrhythmia or conduction system abnormality (evolving complex ventricular ectopy, sustained supraventricular tachyarrhythmia, new left bundle branch block, second- or third-degree heart block)

Systolic blood pressure greater than 250 mm Hg Diastolic blood pressure greater than 120 mm Hg Fall in systolic blood pressure greater than 20 mm Hg Chronotropic insuf ciency in absence of blockers Saturation of oxygen (SpO2) less than 80% Cadence cannot be sustained above 40 rpm Subject requests to stop despite encouragement owing

to symptoms of dyspnea or leg or global fatigue or otherwise

After a maximal exercise maneuver it is essential that the patient continue to pedal with unloaded or low resistance on the bicycle to maintain venous return, particularly in patients with primary or secondary pulmonary hypertension who are particularly prone to postexercise hypotension and syncope. A rule in our laboratory is that you are either pedaling or you are rapidly assisted off the bicycle into a reclining chair with a capability for leg elevation if necessary.

INTERPRETATION

Normal Reference ValuesOnce a test has been reviewed for quality, the next step is to decide if individual test parameters fall within or outside

the normal range. This step involves comparison of results to reference values derived in healthy subjects (normal values), a dif cult problem in the interpretation of PFTs (Miller et al, 2005a; 2005b).1-3,14,15 Unlike blood pH, which has a narrow range of normal, PFT parameters vary greatly in normal people and are, in part, dependent on anthropometric values such as height, age, gender, and racial and ethnic background. It is best to use a reference equation derived from subjects with anthropometric values and ethnic and racial background that matches the patient being tested. Height and weight are measured at the time of testing (shoes removed), not reported by the patient. The reference values used are stated in the PFT report, citing the authors last name (or organization) and year of publication.3 Because subjects of extreme height or age are more sparsely represented in the published refer-ence cohorts, normal values in this range may be particularly suspect; and a statement needs to be included in the inter-pretation stating so.

The signi cant variation in published normal prediction equations is generally underappreciated, particularly with respect to measures of lung volume and DLCO.16 The lack of attention to the speci c normal reference equation can be particularly problematic with respect to cross-center validity in predicting outcome or perioperative risk. For example, the NETT determined that a DLCO of less than 20% predicted in the setting of an FEV1 less than 20% of predicted using Crapo normal equations determined a patient at excessively high risk for lung volume reduction surgery. Use of normal reference values other than Crapos set may result in signi -cantly different values that may have different implications with respect to risk. For example, a 5-foot, 9-inch 50-year-old man undergoing preoperative assessment for lung volume reduction surgery who had a measured DLCO of 6.3 mL/min/mm Hg would have a value calculated as 18% of predicted using Crapos normal value (35.0 mL/min/mm Hg) for an

Flow

(L/s)

45 4 3

HEALTHY NORMAL

TLC

Volume (L)

exerciserest

IC

RV

2

4

5

6

3

3

2

2

1

1

0 Flo

w (L

/s)

4

6567 4 3

COPD PATIENT

Volume (L)

exerciserest

IC

2

4

6

8

2

2

0

PredictedRestExercise

FIGURE 3-8 Left, Tidal ow volume loops at rest and with exertion (small loops) superimposed on the maximal ow volume loop. Note IC increases during normal exertion. Right, The dynamic hyperin ation during exercise in patients with COPD.

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Chapter 3 Pulmonary Physiologic Testing 29

individual of similar age, height and weight, suggesting a potentially excessive risk. On the other hand, false reassur-ance would be achieved using Millers (30.5 mL/min/mm Hg) or Burrows (24.5 mL/min/mm Hg) published equations, resulting in the value reported at 21% and 24% predicted, respectively. Similar attention also needs to be paid to spe-ci c normal equations cited when translating prognostic results from literature de ning risk assessment in other potentially high-risk populations.

Determination of Normal RangeThe time-honored approach has been to consider a xed percentage above and below a predicted value to be the normal range. In general, 80% to 120% of predicted has been the standard used for FVC and FEV1, although wider ranges are commonly used for other parameters (Table 3-3). This approach, although much more easily applied in a basic inter-pretation scheme, has been criticized as being statistically unsound.14 Recent guidelines suggest the assessment of the con dence interval describing a range between the 5th and 95th percentiles of the reference population as being within the normal range.3 The time-honored approach, of using percent of predicted for determining the normal range, most approximates the results using the con dence interval approach in middle-aged individuals of typical height. However, even adhering to the statistically more sound con- dence interval approach to interpretation in patients at the extremes of height or age, available normal reference values may be unreliable because such individuals may not be well represented in the population from which the prediction equation was derived.

Regardless of the approach, test parameters in patients with mild disease are likely to overlap the values found in

normal individuals. Thus, clinical context is necessary when interpreting values near the low or high range of normal. It is appropriate under these circumstances to express the uncertainty in the report, consider ordering additional tests (e.g., lung volumes or bronchoprovocation for borderline obstructive cases), or start empirical therapy with serial PFT assessment.

Ethnic and Racial Differences in Normal ValuesSubjects being tested need to identify their own race or ethnic group. Studies in populations of African or Asian ancestry nd lower predicted values for a given age or height compared with equations derived in populations of European ancestry (resulting in a given African or Asian measurement being reported as a higher percentage of predicted when using these race-speci c reference equations compared with use of unadjusted European ancestryderived equations).3,15,17 On average, factors accounting for such differences appear to be related to shorter torsos for a given height, but socioeco-nomic factors and body mass index may contribute. To avoid these errors, race- and ethnic-speci c reference equations are used whenever possible and indicated in the report.3 Spiro-metric reference values from the National Health and Nutri-tion Examination Survey (NHANES III),18 the recommended reference set of the 2005 ATS-ERS guidelines for interpreta-tion of PFTs, provide different reference equations for male and female Americans of European-American, African-American, and Mexican-American populations.

An alternative to race-speci c equations is to use adjust-ments to the most widely used prediction equations derived in populations of European ancestry. When using prediction equations from a European ancestry population, the following adjustments can be made for patients of African ancestry: FEV1, FVC, and TLC, 12% lower; FRC and RV, 7% lower; FEV1/FVC, no change; DLCO, 2 mL/min/mm Hg or 7% lower.3,4,14 Individuals of mixed racial ancestry have interme-diate values. A race and ethnic adjustment factor of 6% for Asian Americans has been suggested.17,19 These adjustments may not be appropriate for those of Asian ancestry raised in the United States on Western diets.

Height Assessment in the Setting of Spinal Deformity or Leg AmputationWith spinal deformities such as kyphoscoliosis, or in the setting of leg amputation, arm span from ngertip to ngertip measured with the subject standing against a wall can be used as an estimate of height. Although ratios such as height = arm span/1.06 perform reasonably well, there are more accurate regression equations using arm span, race, sex, and age (Miller et al, 2005b).2,20 The use of knee height is an option for those who cannot stand.2,21,22

Age and PFT ValuesThe lung grows throughout childhood, and PFT parameters increase in parallel, reaching a peak in late adolescence or in the third decade of life. Female subjects attain peak PFT values earlier than male subjects, but these are numerically smaller even when adjusted for height. After the peak, most

TABLE 3-3 Normal Predicted Ranges of Selected Pulmonary Function Variables, as Percentage of Predicted*

Parameter Normal Range, % Predicted

FEV1 80-120

FVC 80-120

FEV1/FVC >0.70

FEF25-75% >65 of predicted or FEF25-75%/FVC >0.66

TLC 80-120

FRC 75-120

RV 75-120

DLCO 75-120

*Upper and lower limits are approximate; lower and upper fth per-centile or 95% con dence intervals for these variables are primarily used for deciding if a parameter is outside the normal range, with only a secondary role for percent of predicted.Note: absolute ratio of 0.70 not 70% of predicted ratio. The use of a xed ratio for the lower limit is less useful than one which is based on age, height, and sex.DLCO, diffusing capacity; FEF, forced expiratory ow; FEV1, volume exhaled in the rst second; FVC, forced vital capacity; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity.

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Section 1 Introduction30

test values decline steadily with age. The exception is RV, which increases with aging. As RV increases and VC decreases, TLC remains relatively constant. The FEV1/FVC ratio declines with age, being highest in young children and decreas-ing through adolescence and beyond as lung elastic recoil declines.

Patterns of AbnormalityFigure 3-9 offers a simpli ed algorithm for classifying PFT patterns derived from the 2005 ATS-ERS standards.3

Obstructive PatternThe distinction between obstruction and restriction is based on the FEV1/FVC ratio (or the FEV1/VC ratio) (Figs. 3-1 and 3-10). In the 2005 ATS-ERS standards for interpretation

of pulmonary function tests, an obstructive defect is de ned by an FEV1/VC ratio below the 5th percentile of the pre-dicted value.3 The three ethnic-racial NHANES III equations include an explicit formula for the lower limit of normal for FEV1/FVC.3 Using this method, a normal ratio will be age dependent because the FEV1/FVC ratio declines with age. The VC is de ned as the largest recorded from an IVC, EVC, or FVC maneuver. The FVC may be less than the SVC in patients with obstructive dysfunction because the forced maneuver causes dynamic compression of the airways and premature closure during expiration. For this reason, some areas of Western Europe have used the Tiffeneau index (FEV1/inspiratory VC) as the preferred marker for air ow obstruction.

Other guidelines have chosen to de ne obstruction based on values below an absolute ratio. The National Institutes of Health/World Health Organization GOLD Guidelines for COPD management recommends using a ratio below 0.70 for the diagnosis of COPD, citing the simplicity of this approach and the lack of an internationally accepted set of reference equations.23 The second National Asthma Educa-tion Program Guidelines (1997)24 sponsored by the National Institutes of Health recommends the use of 0.65 as the lower limit of normal for FEV1/FVC. The 2005 ATS-ERS discour-ages the use of a xed FEV1/FVC ratio to de ne the lower limit of normal, citing a high rate of false positive diagnoses of obstructive defects in older patients.3 On the other hand, an argument can be made using the analogy that the presence of a decreased FEV1/FVC in 80-year-olds is no less re ective of age-related disease than the common presence of coro-nary artery plaques in this population.

Caution is needed when a reduced FEV1/FVC ratio is found in a patient with an FEV1 in the normal range. In this situation, particularly when the FEV1 is above 100% of pre-dicted, the low ratio may be a normal variant.3,15 In these cases, the lung volume measurements can be helpful in iden-tifying the presence of hyperin ation associated with obstruc-tive patterns.

Recently, the forced expiratory volume in 6 seconds (FEV6) has been proposed as an acceptable surrogate to the FVC for

Yes

YesYesYes

Yes Yes Yes

Yes

No

No

Normal

Normal

No

NoNoNo

No

No

PVdisorders

CW and NMdisorders

ILDpneumonitis

AsthmaCB Emphysema

FEV1/VC LLN

DLCO

LLN DLCO

LLN DLCO

LLN

TLC LLN TLC LLN

VC LLNVC LLN

Restriction Obstruction Mixed defect

FIGURE 3-9 Interpretation chart. Simpli ed algorithm for interpretation of pulmonary function tests in clinical practice. It presents classic patterns for various pulmonary disorders. Many factors may cause an individual patients studies to fail to conform to this scheme. LLN, lower limits of normal; PV, pulmonary vascular disease; CW, chest wall; NM, neuromuscular; ILD, interstitial lung disease; CB, chronic bronchitis. (FROM PELLEGRINO R, ET AL: INTERPRETATIVE STRATEGIES FOR LUNG FUNCTION TESTS. EUR RESPIR J 26:948-68, 2005.)

Volu

me

(L)

1

1 2

c

b b

a

a

c

3 4 5 6 7 8

2

3

4

5

6

Flow

(L/se

cond

)

1

1 2 3 4 5 6 7 8

2

3

4

5

6

Time (seconds) Volume (L)A BFIGURE 3-10 Volume-time curves (A) and ow-volume curves (B) in normal (c), obstructed (a), and restricted (b) ventilation.

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Chapter 3 Pulmonary Physiologic Testing 31

the assessment of air ow obstruction because serial measure-ments of FVC requiring repeated forceful exhalations to RV can be dif cult and time consuming to obtain. The ATS-ERS guidelines have suggested that 6 seconds is a minimum criterion for acceptable exhalation duration (Miller et al, 2005a).1 The NHANES III reference equations have pro-vided predicted values for FEV6 and FEV1/FEV6 in addition to FVC and FEV1/FVC.4 One study has found the sensitivity of FEV1/FEV6 for diagnosing airway obstruction de ned by FEV1/FVC was 95.0% and the speci city was 97.4%.25 When interpretations differed, the measured values were near the lower limits of the reference range. Potential advantages of the FEV6 include better reproducibility than the FVC, more explicit de nition of the end of test point, and less physical demand on the subject.

Restrictive PatternA restrictive ventilatory defect is de ned as a reduction in TLC below the 5th percentile of the predicted value, accom-panied by a normal FEV1/VC. A restrictive defect may be suspected when spirometry shows a decreased VC, the FEV1/VC is increased (>85%-90%), and the ow-volume curve shows a convex pattern.3 A normal or elevated FEV1/FVC ratio with a low FEV1 or FVC suggests restriction, although lung volumes are needed to con rm true restrictive dysfunction. This is recommended because some with this spirometric pattern have underlying obstructive lung disease.3,14,26,27 This pseudorestriction in patients with asthma or COPD is recognized by hyperin ation on lung volume testing or bronchodilator responsiveness of the restriction. By contrast, those with true restriction have reduced lung volumes (TLC, and often also RV and FRC). As such, VC is very sensitive for restriction but less speci c.26 When examining spirometric results, the likelihood of true restriction increases as FVC decreases and FEV1/FVC increases.26 A normal VC is very good at ruling out restriction.

Mixed Obstructive and Restrictive DefectsThis pattern is de ned by the coexistence of both an FEV1/VC and TLC below the 5th percentile of their predicted values. Both obstructive and restrictive diseases can result in a reduction in VC; therefore, restriction is not diagnosed from spirometry alone without measurement of full lung volumes, including TLC.

Use of Other Flow Parameters in Classi cation of PatternsThe just-stated approach to classi cation into normal versus obstructive versus restrictive versus mixed defect uses only the parameters VC (or FVC), FEV1, FEV1/VC, and TLC.3 In general, other ow parameters re ecting ows at low lung volumes, such as FEF25-75%, FEF50%, and FEF75% have wide ranges of normal and are misleading for classifying a patient as having abnormal or obstructive function on the basis of these parameters alone.3 It is acceptable to classify isolated defects in FEF25-75% (

Section 1 Introduction32

FIGURE 3-11 A, Variable extrathoracic UAO caused by vocal cord dysfunction syndrome is evident on this ow-volume loop. The inspiratory limb of the loop shows attening and ow rates much below the expiratory limb. This functional disorder of vocal cord adduction is also known as functional stridor, factitious asthma, or laryngeal dyskinesia. Some patients have concomitant asthma, but when vocal cord dysfunction is an asthma mimic only inspiratory stridor is present. The ow-volume loop or laryngoscopy establishes the diagnosis. B, Variable extrathoracic UAO. During expiration, the transmural pressure gradient acting across the tracheal wall distends the airway, lessening the obstruction to air ow. On inspiration, the transmural gradient causes critical narrowing and a ow plateau develops. (FROM CLIN CHEST MED 1994; 15:35-53, 1994; ADAPTED FROM AM J MED 61:85, 1976.)

Flow

(L/s)

6 1 2 3 4 5 6 7 8 9

2

4

2

4

8

6

10

12

14

Volume (L)

Expiration

A

B

Inspiration

Ptr > Patm Ptr < Patm

ated with inspiration result in more normal-appearing inspira-tory loops (see Fig. 3-12).

Because diseases causing UAO patterns are uncommon, many suggestive loops will be due to poor effort or can rep-resent a normal variant. Such poor effort is generally associ-ated with lack of repeatability, whereas true abnormalities are repeatable.

High-frequency utter waves (sawtoothing) are some-times superimposed on otherwise normal FVLs in patients with upper airway pathology. This was rst reported in patients with obstructive sleep apnea and initially was thought to be speci c to that condition. Subsequently, it was also

identi ed in patients with neuromuscular disease (due to weak upper airway muscles, particularly in extrapyramidal disorders). The uttering is likely due to vibration of redun-dant or hypotonic tissues in the upper airway or is caused by resonance generated downstream from a narrowed section of airway.

Expiratory ow limitation during tidal breathing is a marker of severe obstructive or restrictive defects. Such a pattern is recognized when a tidal breathing loop, viewed within the maximal effort FVL, manifests as tidal expiratory ow impinging on the maximal expiratory ow curve.

Rating of SeverityOnce the pattern of abnormalities is de ned (obstruction versus restriction), the severity is rated. The 2005 ATS-ERS standards for interpretive strategies for lung function tests outline a rating of severity based on FEV1% predicted for both obstructive and restrictive defects (Table 3-4).3 In general, because VC is reduced proportionate to severity in restrictive defects, FEV1 is appropriate to rate the severity in a similar manner. The GOLD Guidelines for COPD23 introduced a combined severity rating system for educational purposes that differs from the system described earlier by being much more liberal in their ratings of severity. Although commonly employed in clinical practice, such a system is not recommended in the laboratory interpretation of PFTs.

The DLCO has an important independent role in assessing severity in both emphysema and interstitial lung disease (see Table 3-4). Recently, many researchers have suggested that physiologic measures of hyperin ation (RV, TLC) or its indi-rect effects (reduced IC or increased IC/TLC) are indepen-dently associated with symptoms and may further complement other physiologic measures in assessing severity in COPD, although speci c categories based on these parameters have not been described.

Bronchodilator ResponseATS-ERS criteria for de ning bronchodilator response con-siders a signi cant intra-session bronchodilator response to be an increase from baseline FEV1 or FVC greater than 12% and 200 mL.3 Testing is performed before and 10 to 15 minutes after use of a rapid-onset bronchodilator (typically albuterol), delivered as four puffs via a spacer device (Miller et al, 2005a).1,3 When bronchodilator responsiveness is to be assessed, short-acting bronchodilators are stopped for 4 hours and long-acting bronchodilators stopped for 12 to 24 hours before the testing session. If testing is performed to assess the patients maintenance medical regimen, bronchodilators are not withheld. Typically, measurement of DLCO, if ordered, will be performed during the 15-minute window after -agonist administration because results are generally not affected by the bronchodilator (Miller et al, 2005b).2,3

Bronchodilator reversibility has some clinical utility in determining lability of lung function and con rming the pres-ence of a xed obstructive impairment. This testing, however, is neither highly sensitive nor speci c in distinguishing asthma from COPD, does not represent a xed characteristic in an individual patient (because reversibility status commonly

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Chapter 3 Pulmonary Physiologic Testing 33

TABLE 3-4 Rating of Severity of Pulmonary Function Tests Using the Method in the 2005 American Thoracic Society/European Thoracic Society Standards* and Gold Guidelines for COPD

ATS/ERS GOLD PredictedRating FEV1 (%) FEV1 (%) DLCO* (%)

Mild >70 >79 >60 and

Section 1 Introduction34

DLCO, signi cant year-to-year changes of 15% or more are likely meaningful. For idiopathic pulmonary brosis, it has been suggested that a signi cant change in DLCO is 15% or more or greater than or equal to 3 mL/min/mm Hg and that for TLC or VC is 10% or more (or 200 mL).32

With these principles in mind, the treating pulmonologist can best interpret a series of PFT measurements by integrat-ing the clinical scenario. Stable PFTs in a disease expected to be progressive could be interpreted as a sign of effectiveness of therapy. Lack of signi cant improvement in a disease expected to respond well to medication might be interpreted as a failure of therapy. A signi cant change in PFT measure-ments may not be clinically meaningful to a given patient. Serial follow-up demonstrating consistent trends, focusing on the major parameters listed earlier, is likely to be most useful.

Patterns Helpful With Speci c Disease Classi cationTrue Restrictive DisordersThese conditions include the intraparenchymal disorders (interstitial and in ltrative lung disease, diffuse alveolar disease) and chest wall restriction (pleural, skeletal). These processes have the classic ndings of reduced TLC, FRC, RV, and VC and normal to high FEV1/FVC ratio. A spirometric diagnosis of restriction, de ned by a low FVC and an FEV1/FVC ratio greater than 70%, was found to have a sensitivity of 93% but a speci city of only 82% when compared with a plethysmograpy lung volume gold standard.33 This study noted that 10% of pure obstructive defects had restrictive spirometry and thus supports the ATS-ERS recommendation that an interpretation of restriction from spirometry requires con rmation by full lung volume measurements. A more cau-tious term for such spirometric patterns when full lung volumes have not been measured is a nonspeci c defect.

Neuromuscular DiseaseThese patients generally have a normal lung and chest wall but weakness of the inspiratory muscles (mainly the dia-phragm) and the expiratory muscles (mainly the abdominal muscles), which limits inspiratory and expiratory deviation from the resting lung volume (FRC). Consequently, the char-acteristic abnormality is a reduction in VC caused by reduc-tion in both IC and ERV. The reduced IC, with a normal FRC, results in a reduced TLC (and hence is restrictive). The reduced ERV, with a normal FRC, results in an increased RV in those with more severe weakness. This elevation of RV in the setting of decreased VC and increased RV distinguishes the restriction of neuromuscular disease from true restric-tive disorders.

Patients with isolated or disproportionate bilateral dia-phragmatic weakness or paralysis show a marked fall in VC in the supine compared with the erect posture. This re ects the effects of gravitational forces on abdominal contents in the two positions. In the normal subjects the VC falls 5% to 10% in the supine position. A fall of 30% or more is associ-ated with severe diaphragmatic weakness, and the postural fall may exceed 50% in some subjects.

Although the MIP and MEP are the more speci c and sensitive tests for muscle weakness, the simpler and more accessible VC is most often followed in neuromuscular disease patients. VC is also sensitive for assessing the progres-sion from moderate to severe respiratory muscle weakness. The rate of decline in VC predicts survival in both amyo-trophic lateral sclerosis and Duchenne muscular dystrophy. Although, in general, MVV has no advantages over VC, in some patients with Parkinsons disease the MVV may be reduced disproportionately to VC.

Pseudorestriction Associated With Obesity and AsthmaPatients with obesity or asthma may have spirometric nd-ings that may be confused with those associated with true restrictive disorders. FVC may be low with a normal or ele-vated FEV1/FVC ratio.

With obesity, the associated reduction in chest wall and abdominal compliance also results in a mild fall in VC as well as FRC and TLC.34 In contrast to true restriction, however, abdominal compression of the lower lung leads to early airway closure and a low ERV with elevated RV and reduced mid-expiratory ow (FEF25-75%).35

Clues to distinguish a pseudorestrictive pattern in asthma from true restriction and from the pseudorestriction of obesity include the following:

Signi cant improvement of FEV1 or FVC before and after bronchodilator spirometry

Elevated FRC and TLC (RV can be low or high in obesity)

Improved restriction with asthma therapy Very low ERV, forced ERV Positive bronchoprovocation test Elevated DLCO and DLCO/VA

Causes of pseudorestrictive spirometry in asthma may be related to complete airway occlusions due to mucus plugging or dynamic premature airway closure such that FVC is reduced proportionate to FEV1, resulting in a normal FEV1/FVC ratio. In addition, incomplete expiratory effort on the FVC or failure to inspire completely to TLC before the expiratory blast will result in undermeasurement of the FVC. Although the low FEV1 and FVC and normal ratio may be mistaken for restriction, the short expiratory time, lack of an expiratory plateau, hyperin ation on lung volume measure-ments, and scooped-out FVL indicate that the true disorder is obstructive.

Diseases With Mixed Obstructive and Restrictive DefectsDiffuse interstitial or in ltrative lung disease typically causes restrictive patterns with normal or high FEV1/FVC and reduced lung volumes (TLC, FRC, RV). Obstructive ventila-tory defects can be seen in traditionally restrictive processes such as sarcoidosis, rheumatoid lung disease, and advanced idiopathic pulmonary brosis. This may be due to granulo-matous airways disease (e.g., sarcoidosis), bronchiolitis (e.g., rheumatoid lung), or airway distortion from severe parenchy-

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Chapter 3 Pulmonary Physiologic Testing 35

mal brosis or cystic spaces with honeycombing in any advanced interstitial lung disease.

Bronchiectasis causes reduced expiratory ow rates as a result of total obliteration of some airways and increased collapsibility of dilated, patent airways. However, reduced TLC (restriction) is often present due to brosis of paren-chyma in the bronchiectatic lung segments. Certain diffuse in ltrative diseases (e.g., eosinophilic granuloma and lymphan-gioleiomyomatosis) are typically associated with air ow obstruction and increased volumes.

Although bronchiolitis is an airway disease, proliferative bronchiolitis, such as bronchiolitis obliterans organizing pneu-monia, usually has a restrictive pattern. Mixed patterns can be seen in smokers. In contrast, constrictive bronchiolitis, such as transplant-associated bronchiolitis and diffuse panbronchiolitis, usually has an obstructive pattern with hyperin ation.

Disease Processes Causing Abnormalities of Diffusing CapacityThe DLCO is decreased in conditions that disrupt the alveolar-capillary surface for gas transfer. This can occur due to loss of surface area (pulmonary resection, pulmonary bro-sis, emphysema, pneumonia); reduced lung capillary volume (pulmonary vascular disease including vasculitis, pulmonary thromboembolism, and primary pulmonary hypertension and also in emphysema and interstitial lung disease); or increased diffusion distance (pulmonary alveolar proteinosis, Pneumo-cystis carinii pneumonia).

The most sensitive tests for demonstrating abnormalities in early or mild interstitial lung disease include DLCO and P(A a)O2 during exercise, both of which may be abnormal when spirometry, lung volumes, and blood gases at rest are normal.36 Other causes of an isolated reduction in DLCO include disease of the pulmonary vascular compartment (primary or thromboembolic pulmonary hypertension, or pulmonary vasculitis). Recent data indicate that we also need to consider emphysema in this setting.37 In contrast to the low DLCO seen in emphysema, asthmatics tend to have ele-vated values.38

DLCO can be increased by conditions that lead to recruit-ment of the pulmonary vascular bed and an increase in capil-lary blood volume (exercise, mild congestive heart failure, left-to-right shunt, asthma) or by an increased amount of hemoglobin, which binds CO (pulmonary hemorrhage, eryth-rocytosis). The increased DLCO in asthma is most likely due to increased capillary blood volume induced by the single breath maneuver when the asthmatic takes a forced inspira-tory VC against high airway resistance before performing the breath-hold.

Cardiac Effects on PFTsThe relationship between lung function and cardiac events has been documented in the Framingham longitudinal studies, which found that reduced FVC is an independent predictor of cardiac events even in people without established cardiac disease. In patients with congestive heart failure, the PFT ndings are well explained by the mechanisms and stages of

pulmonary congestion. In mild stages, with vascular conges-tion but without frank pulmonary edema, the increased capil-lary blood volume will result in an increased DLCO. With more blood volume (and hemoglobin) to accept CO and nothing interfering with the transfer of gas from alveolus to capillary, uptake of CO is enhanced. As congestion worsens with the development of interstitial and alveolar edema, a restrictive process with a reduced DLCO develops.39 In chronic congestive heart failure, pericapillary hemosiderosis and brosis can result in a stable drop in DLCO.40

Amiodarone pulmonary toxicity is a dif cult diagnosis to establish. Although serial PFTs, including the measurement of DLCO, have not proven useful in screening for early disease, otherwise unexplained restriction and low DLCO is part of the clinical pattern suggesting toxicity from this drug.

BronchoprovocationFEV1 and PEF rate are good measures of asthma severity and measure the degree of air ow obstruction. A related but dis-tinct aspect of asthma is the degree of twitchiness of the airways, known as airway hyperresponsiveness. This tendency to bronchoconstriction can be assessed for speci c antigens, although it is more common to assess nonspeci c hyperre-sponsiveness in the laboratory with pharmacologic agents (methacholine or histamine), exercise (exercise-induced bronchospasm), or cold dry air inhalation (which is often combined with exercise). Although these techniques are complementary in yield, the pharmacologic agent methacho-line is most frequently used.

Methacholine Challenge TestingClinically, this test is most commonly used to diagnose asthma in patients who have had normal results of routine PFT studies yet have symptoms that may suggest asthma. When symptoms are typical, an empirical course of treatment for asthma is a reasonable alternative. Cough-variant asthma fre-quently presents as monosymptomatic cough without wheeze and with normal routine PFT results.

Patients inhale concentrations of methacholine, doubling from 0.05 mg/mL up to 25 mg/mL, with measurement of FEV1 after each concentration. The results are graphed as the percent reduction in FEV1 from baseline versus inhaled con-centration. The concentration of inhaled agent that causes a 20% reduction in FEV1 (PC20-FEV1) is interpolated from the graph. The ATS guidelines have suggested cutoff points for interpretation that vary relative to the ordering physicians pretest probability (Crapo et al, 2000).41 Assuming a pretest probability of asthma of 30% to 70%, a PC20-FEV1 greater than 16 mg/mL is normal; 4.0 to 16 mg/mL is borderline bronchial hyperresponsiveness (BHR); 1.0 to 4.0 is mild BHR (positive test); less than 1.0 mg/mL is considered moderate to severe BHR. The threshold below which a test is consid-ered positive shifts to higher concentrations when the pretest likelihood of asthma is higher. Conversely, a lower concentra-tion is required to designate a test positive when the pretest suspicion of asthma is lower, such as in population screening.

The test is also sometimes performed using the body ple-thysmograph to measure airways resistance (Raw) and its

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Section 1 Introduction36

reciprocal, conductance (Gaw). This is usually expressed as speci c airway conductance, G/TGV (conductance divided by the thoracic gas volume at which it is measured). A 45% reduction in Gaw is considered positive due to greater vari-ability in this measurement than for FEV1.

Most consider bronchoprovocation highly sensitive for asthma but nonspeci c. Consequently, a negative test is a strong argument against the diagnosis of asthma. False-negative ndings can be due to currently inactive or ade-quately treated asthma. Bronchoprovocation is not useful in distinguishing asthma from COPD because there is a high prevalence of airway hyperresponsiveness in tobacco-related COPD. The lower the PC20, however, the more likely it is that the patient has asthma. A negative methacholine study can be used as supportive evidence for vocal cord dysfunction mimicking asthma, especially if a attened inspiratory limb of the FVL is present.

Exercise BronchoprovocationAssessment for exercise-induced bronchospasm can be per-formed as an add-on to CPET or as a separate diagnostic maneuver. Testing for EIA in the laboratory is only moder-ately sensitive because conditions may not mimic the cold and dry air conditions or the pattern of ventilation present under eld conditions. Therefore, methacholine challenge testing always needs to be the rst bronchoprovocation study, even in subjects with suspected exercise-induced broncho-spasm, because it is also simpler to perform and more sensitive for the diagnosis. Some patients will demonstrate hyperresponsiveness to exercise or cold air challenge testing who do not react to methacholine. Exercise bronchoprovoca-tion is best performed on the treadmill, with a target heart rate of 80% to 90% of predicted maximum (220 age in years) maintained for 4 to 6 minutes, with a total exercise duration of 6 to 8 minutes. Spirometry measurements are made before and then every 5 minutes for 20 minutes after the exercise maneuver.42 A drop in FEV1 of greater than 15%

is considered diagnostic. Having the patient inhale cold, dry air during the study increases the yield of this test.

CLINICAL UTILITY OF CARDIOPULMONARY EXERCISE TESTING

Unexplained or Disproportionate DyspneaCardiopulmonary exercise testing can be useful in document-ing impairment and distinguishing abnormal cardiopulmonary physiologic responses from inorganic causes associated with anxiety or even malingering when routine history, physical, basic PFTs, and laboratory tests fail to determine a cause of dyspnea (Fig. 3-13).36,43 A normal study can serve to reassure the patient and avoid expensive and invasive testing. An abnormal study may direct the workup toward more invasive testing, such as right- or left-sided heart catheterization, pul-monary angiography, lung biopsy, or muscle biopsy or indi-cate speci c therapy such as exercise training, bronchodilators, or angiotensin converting-enzyme inhibitors. Because of the wide variation of normal values, serial tests in the setting of persistent or progressive symptoms may be necessary to document progression of an abnormal physiologic response. CPET can be useful in determining relative contributions of cardiovascular and ventilatory abnormalities to exercise impairment in patients with known disease. Such determina-tions can direct therapy to the appropriate organ system.

Assessment of InterventionCardiopulmonary exercise testing has shown promise in the research and clinical arenas in the assessment of physiologic and functional change associated with an intervention. CPET not only offers greater insight into speci c physiologic changes than resting testing but also allows assessment of the inte-grated response of varying effects of the intervention on the system. For example, in the assessment of exercise response to lung volume reduction surgery, a given individual may demonstrate increased tidal volume and lower respiratory

0.21VD/VT

34PCO2

5BE

92O2 pulse

50%AT % VO2 pred

0.62VE-max/MVV

95%HR %pred

71%VO2 max %

98%FEV1 %pred

180

60

140

100

100

60

20

VO2 mL/min300020001000

HR

1/m

in VE L/m

in

NORMAL RESPONSE

A

FIGURE 3-13 A to D, Patterns of cardiovascular and ventilatory response during exertion. AT % VO2 pred, anaerobic threshold as a percentage of predicted maximal oxygen consumption; BE, change in base excess; HR %pred, heart rate response as a percentage of predicted; O2 pulse, oxygen consumption/heart rate; VD/VT, dead space to tidal volume ratio; VE-max/MVV, maximal exercise ventilation as a proportion of maximal voluntary ventilation; VO2 max %, maximal oxygen consumption as a percentage of predicted.

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Chapter 3 Pulmonary Physiologic Testing 37

VD/VT

PCO2

BE

O2 pulse

AT % VO2 pred

VE-max/MVV

HR %pred

VO2 max %

FEV1 %pred

180

60

140

100

100

60

20

VO2 mL/min300020001000

HR

1/m

in

VE L/m

in

0.24

32

7

58

39%

0.47

102%

66%

87%

PURE CARDIOVASCULAR LIMITATION

B

VD/VT

PCO2

BE

O2 pulse

AT % VO2 pred

VE-max/MVV

HR %pred

VO2 max %

FEV1 %pred

180

60

140

100

100

60

20

VO2 mL/min300020001000

HR

1/m

in

VE L/m

in

0.47

48

2

81

NA

0.92

77%

62%

47%

PURE VENTILATORY LIMITATION

C

VD/VT

PCO2

BE

O2 pulse

AT % VO2 pred

VE-max/MVV

HR %pred

VO2 max %

FEV1 %pred

180

60

140

100

100

60

20

VO2 mL/min300020001000

HR

1/m

in

VE L/m

in

PULMONARY VASCULAR DISEASE

0.42

26

5

62

36%

0.53

98%

72%

97%

D

FIGURE 3-13, contd

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Section 1 Introduction38

rates, lower VD/VT, and increased IC associated with less dynamic hyperin ation; however, an earlier-onset lactic aci-dosis and elevated heart rate/oxygen consumption relation-ship due to simultaneous excision of the pulmonary vascular bed may balance the bene cial pulmonary mechanical effects and result in no change or deterioration in V

.O2max or maximal

watts. Exercise testing has been used to document the effects of bronchodilators in COPD,44,45 immunosuppressive therapy in idiopathic pulmonary brosis,46 lung transplantation in COPD,47 lung volume reduction surgery,48 and prostacyclin therapy in primary pulmonary hypertension.49

DETERMINATION OF PROGNOSISMeasurements of maximal oxygen consumption are predic-tive of survival in individuals with cystic brosis, congestive heart failure, and COPD.50 Patients with cystic brosis with V.

O2peak less than 59% predicted were more than three times as likely to die as those with values greater than 82% of pre-dicted, whereas measures of resting pulmonary function did not independently correlate with survival.51 Individuals with cardiomyopathy awaiting heart transplantation who have V.

O2peak greater than 14 mL/min/kg demonstrate a 94% one-year survival compared with 70% of those individuals with values less than 14 mL/min/kg.52 Based on these data, indi-viduals with values for V

.O2peak less than 14 are prioritized

in consideration for heart transplantation.The National Emphysema Treatment Trial strati ed severe

emphysema patients into subgroups, based on patterns of exercise response. Patients who had a high mortality rate in the control group based on low incremental cycle ergometry watts (de ned earlier) experienced a greater than 50% reduc-tion in mortality rate if they had upper lobe dominant disease, whereas patients in the high-exercise category were not likely to experience a survival bene t. The high-exercise responders, however, still experienced improved exercise tol-erance and quality of life if they had upper lobe dominant disease. The role for CPET measurements in the assessment of preoperative risk before thoracotomy are discussed in Chapter 2, and in this situation low maximal V

.O2 meas-

ures can de ne subgroups of patients at excessively high risk for surgery, and higher V

.O2 measures de ne subgroups

at acceptable risk despite traditionally unacceptable FEV1 levels.53-55

Disability AssessmentAlthough clear guidelines for determination of disability are lacking, it is clear that resting pulmonary function measure-ments do not adequately predict functional status. In a group of subjects studied who met ATS guidelines for respiratory disability, 48% had slight or no disability measured using CPET.56 One standard commonly used in determination of disability is to compare oxygen consumption measurements in the laboratory to published energy requirements for

different jobs57; the average energy requirement on the job does not exceed 50% of an individuals maximal work capacity.

Pulmonary RehabilitationThe use of CPET before pulmonary rehabilitation is recom-mended to de ne safety and determine exercise prescription. CPET allows supervised observation of potential ischemia, arrhythmia, and desaturation before training sessions.58-60

COMMENTS AND CONTROVERSIESIt is critical that thoracic surgeons understand clearly the measure-ment of pulmonary physiology (both mechanical properties and gas exchange). Interpretation of results and integration of data into a treatment plan is impossible without this knowledge. Drs. Sciurba and Salzman have produced an excellent review with practicality in mind.

Spirometric evaluation of FEV1 and FVC and pitfalls in their mea-surement are discussed. The de nitions of lung volume and capaci-ties are essential information. The techniques of their measurement (plethysmography and gas dilution) are described, and pitfalls are noted. It is important for thoracic surgeons to note that gas dilution and wash-out techniques underestimate FRC, RV, and TLC in patients with severe inequality in distribution of ventilation (e.g., airway disease or COPD).

The potentially confusing measurement of DLCO is discussed, and the importance of hemoglobin level and current smoking on the measurement of DLCO is emphasized.

Considerable attention is devoted to cardiopulmonary exercise testing and its limited role in the evaluation of thoracic surgical patients.

Of course, the interpretation of results requires knowledge of the predicted normal values used for comparison. An informative dis-cussion of