Vous êtes sur la page 1sur 20

chapter

PULMONARY PHYSIOLOGIC TESTING


Frank C. Sciurba
Steve H. Salzman
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 ventilation, maximal respiratory pressures, and lung compliance.
Cardiopulmonary exercise testing not only delineates the reserve
of each of the contributing subcomponents of the process of respiration 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.

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 mechanical structure and as a gas-exchanging surface. Clinical pulmonary 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 assessment of severity of lung disease and is critical in the
determination of perioperative risk. Cardiopulmonary exercise testing (CPET) may offer further diagnostic and prognostic advantages over resting assessment of the respiratory
system because it measures physiologic reserve and integrated 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 TESTING
Pulmonary 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 specic 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,

compliance, resistance, respiratory pressures, airway hyperreactivity, 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
(DLCO), and physiologic dead
. capacity
.
space ventilation (VD/VT). Various lung diseases, or individual 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.

SPIROMETRY
Spirometry is the most commonly performed and standardized 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 exhalation, dened as slow vital capacity (SVC). Forced exhalation 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 classication, 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 spirometry cannot measure the air remaining in the lung after a
complete exhalation, are often linked to tests of lung volume
(Fig. 3-2).
19

Ch003-F06861.indd 19

1/21/2008 10:19:55 AM

20

Section 1 Introduction

8.0

8.0

6.0

7.0
TLC
6.0

4.0

RV

TLC

2.0

FVC

3.0

FIF50

4.0

2.0

6.0

1.0

RV

0.0

8.0
7.0

4.0

5%

FVC

FEV1

257

0.0

FEF

Flow (L/s)

5.0
Volume (L)

FEF50

2.0

FEV1

6.0

5.0

2.0
3.0
Volume (L)

2.0

0.0

1.0

1.0

2.0

3.0

4.0

Time (sec)

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 airow 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.
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

Lung volumes and capacities

IC

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

Technique and Specic Methodology


The forced maneuver consists of three distinct phases (Miller
et al, 2005)1:
1. Maximal inspiration
2. A blast of exhalation
3. Continued complete exhalation to the end of test (until
no more air can be exhaled but maintaining an upright
posture)

Ch003-F06861.indd 20

IC

IRV

TLC

SVC
TV
ERV ERV
FRC
RV

RV

RV

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.

It is then followed by a rapid inhalation back to full inspiration. This effort can be shown graphically as a ow-volume
loop (FVL) or volume-time curve (V-t curve), both representing the same FVC maneuver (see Fig. 3-1). Enthusiastic
coaching by the technician, including appropriate body language 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 completely 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 associated with reductions in FEV1 and peak expiratory ow
(PEF).

1/21/2008 10:19:55 AM

Chapter 3 Pulmonary Physiologic Testing

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 Criteria


Clinicians using parameters derived from these maneuvers
need to become familiar with acceptable quality control standards, 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 individual 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 transients 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

21

TABLE 3-2 2005 American Thoracic SocietyEuropean


Respiratory Society Acceptability Criteria for Spirometry*
Within Maneuver
Smooth 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 <5% of FVC or 150 mL, whichever is larger
No hesitant start; ow-volume curve with a sharp rise to peak
ow
Note: FEV1 can be over- or under-measured with submaximal
effort
Satisfactory end of test (keep going, keep going)
Plateau of 1 second on volume-time curve (no further volume
exhaled despite continued expiratory effort)
or
Reasonable duration of effort:
6 seconds in subjects >10 years
3 seconds in subjects <10 years
Exhalation times >15 seconds will rarely change clinical
decisions
or
Subject cannot or should not continue further exhalation
Between Maneuver
After 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.
*Modied from Miller MR, Hankinson J, Brusasco V, et al: Standardisation of spirometry. Eur Respir J 26:319-338, 2005.

10.0
Sharp peak
8.0
Plateau
6.0
Continuous
curve

4.0

Artifacts
(glottic closure)

Rapid rise
(blast)

4.0
Good start

Gradual return
to 0 flow

0.0
2.0

Slow rise

Abrupt end
flow

Incomplete
inhalation

Smooth
inhalation

4.0

Hesitant
start

0.0
0.0

1.0

2.0
3.0
Acceptable loop

4.0

4.0
Inadequate loop

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

Ch003-F06861.indd 21

1/21/2008 10:19:56 AM

22

Section 1 Introduction

expressed quantitatively as extrapolated volume and often


printed in the numerical section of the report.
The ATS-ERS criteria for spirometry apply withinmaneuver 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 acceptability 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 Data


The 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 specic
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 exhalation and no cough in the rst second (usable curves),
although the condence 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 MEASUREMENTS


As 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.

Denitions
The 2005 ATS-ERS standards on lung volumes employed the
following denitions.4 A lung volume parameter is termed a
volume if it cannot be broken down into smaller subcomponents (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).

Ch003-F06861.indd 22

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 RV
Total 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 nonspecic and is replaced with more specic terminology, such as FRC by body plethysmography or TGV at FRC
(FRCpleth).

Body Plethysmography
Plethysmographic 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 mouthpiece (Fig. 3-4). During the test an electronic shutter temporarily 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 (reected in Pbox).

1/21/2008 10:19:56 AM

Chapter 3 Pulmonary Physiologic Testing

FIGURE 3-4 Body plethysmography.

Body Plethysmograph Method


for Determination of FRC

23

Mouth pressure (Pm)


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

Electrically
controlled shutter,
closed at
end-expiration

FRC

Box pressure (Pm)


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

Patient makes
panting efforts
against closed
shutter

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 Dilution
The 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 concentration (C1) volume of spirometer [V1]) is known at the beginning 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.

Ch003-F06861.indd 23

Technique and Specic Methodology


In 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 (geometric) 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 distribution of ventilation, such as those with severe airways disease.
Regions of lung with long-time constants (directly proportional 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, plethysmographic 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 measurements 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 plethysmographic techniques in patients with severe airow limitation.
In these cases, severe airow obstruction may result in phase

1/21/2008 10:19:56 AM

24

Section 1 Introduction

BODY PLETHYSMOGRAPHY TECHNIQUE


TLC
Shutter closure
a

IC
ERV

Mid-rest position
RV
True
FRC

False high FRC


by amount a

O
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 ination 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 dene 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.

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 measurement of FRCpleth. Fortunately, this small error is in the
direction that enhances the ability to recognize the
underlying disease (i.e., the degree of hyperination 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 ATSERS 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 measurements 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 technically 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 Capacity
The 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

Ch003-F06861.indd 24

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 transfer 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 concentration alone without the measurement of blood CO (except in
the tobacco user).

Technique and Specic Methodology


The widely accepted technique used to measure DLCO, utilized in virtually all clinical laboratories, is the single-breath
methodology, whereas historically, and still in research settings, other steady-state techniques are utilized. In the singlebreath 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 dilutional 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
(reecting an alveolar sample) is collected and analyzed. Measurement of the initial (inspired) and nal concentration

1/21/2008 10:19:56 AM

Chapter 3 Pulmonary Physiologic Testing

(exhaled) of CO adjusted for gas dilution and breath-hold


time determines DLCO.

OTHER PULMONARY FUNCTION TESTS

Acceptability, Repeatability, and Number of Tests

To 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 interpretation of ventilatory reserve during CPET. In subjects who
achieve a ventilatory limitation, such as patients with severe
chronic obstructive pulmonary disease (COPD) or respiratory muscle weakness, maximal exercise ventilation (VEmax)
often approaches or exceeds MVV (VEmax/MVV > 0.75).
MVV is commonly estimated from simple spirometric measures (40 FEV1).

Acceptable 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 DLCO
Be wary of DLCO values that are reported without adjustment 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 adjustment 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% adjustment; 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 considers 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 Volume


It 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 vascular 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 neuromuscular 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 disproportionately greater abnormality in gas exchange (low
DLCO/VA).7

Ch003-F06861.indd 25

25

Maximal Voluntary Ventilation

Maximal Respiratory Pressures


The most specic tests to identify neuromuscular weakness
as the cause of restriction are the maximal inspiratory pressure (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 expiratory 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 effortdependent 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 emphysema associated with lung hyperination and suboptimal
respiratory muscle congurations. 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 hyperination.

1/21/2008 10:19:57 AM

26

Section 1 Introduction

Lung Compliance
Although 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 reects 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 represents 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 coefcient of retraction, 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 emphysema is a reection of the intrinsic loss of elasticity. The
normal range for PEL(L)/TLC is 2 to 8 cm H2O/L.

CARDIOPULMONARY EXERCISE TESTING


Parameters traditionally considered to be the gold standards
of cardiopulmonary function such as FEV1 and cardiac ejection fraction often correlate poorly with symptoms or exercise capacity, and changes in these resting parameters after
an intervention often do not reect functional improve-

ments.8,9 Exercise testing not only delineates the reserve of


each of the contributing subcomponents of the process of respiration 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 Capacity


In normal individuals and patients with cardiac abnormalities,
exercise termination occurs at the maximal oxygen consumption (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 recognition 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 homeostasis under all but the most severe internal disease conditions 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 Exertion


Emphysema

Volume (L)

Although there is considerable variability in the heart rate


response to exertion in normal individuals, heart rate normally 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).

Normal

3
Fibrosis
2

Ventilatory Response During Exercise

.
Increases in minute ventilation (VE) during exertion are necessary to maintain systemic blood gas and acid-base homeostasis. The formula describing the effect of changes in various
factors on minute ventilation requirements is:

0
0

30
10
20
Distending pressure (cm H2O)

40

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.)

Ch003-F06861.indd 26

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

The level of minute ventilation required will depend on


the central set point for PaCO2, which is inuenced by central
drive, vagal afferents, and humoral input (including pH and
PaO2), the CO2 production, and the dead space proportion.

1/21/2008 10:19:57 AM

Chapter 3 Pulmonary Physiologic Testing

.
Therefore, the rate of increase in VE 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) identied as the ratio VD/VT.
Lactic acidosis associated with increasing exertion .in both
normal and cardiac-impaired individuals can drive VE 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 calculate the dead space proportion using the equation:
VD/VT = (PaCO2 PECO2)/PaCO2

where PECO2 represents the mixed expired CO2


concentration.
.
Maximal values of VE achieved during exertion are normally 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 VE is commonly compared. with the MVV to
assess the ventilatory
reserve, expressing VE as a percentage
.
of MVV. A VE/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 Volume
The end-expiratory lung volume (EELV) in normal individuals decreases with exertion, but COPD patients experience dynamic hyperination during exertion due to an

Normal

27

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 calculated as the difference between TLC and IC. Improvement
in dynamic hyperination has been documented after bronchodilator therapy and lung volume reduction surgery.

Impact of Exercise Protocol on Outcome


It 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 predened 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 exercise power output (watts) during incremental bicycle testing
can vary dramatically with other seemingly subtle changes in
exercise protocol. For example, the exercise protocol dened
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 specically dened
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

FIGURE 3-7 Ventilatory limit.

(MVV)

VE

VE

Ventilatory
reserve
(MVV)

Work Rate or VCO2

Work Rate or VCO2

Ch003-F06861.indd 27

Alveolar ventilation

VE = Minute ventilation

Dead space

MVV = Maximal voluntary ventilation

1/21/2008 10:19:57 AM

28

Section 1 Introduction

HEALTHY NORMAL
6
5

Predicted
Rest
Exercise

6
4

Flow (L/s)

Flow (L/s)

1
0

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 hyperination
during exercise in patients with
COPD.

COPD PATIENT
8

TLC

2
0

RV

2
4
3
4

6
5

4
3
Volume (L)

5
4
Volume (L)

rest
IC

exercise

Safety Issues
Standard 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, secondor 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 insufciency 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 Values
Once a test has been reviewed for quality, the next step is
to decide if individual test parameters fall within or outside

Ch003-F06861.indd 28

rest
IC

exercise

the normal range. This step involves comparison of results to


reference values derived in healthy subjects (normal values),
a difcult 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 reference cohorts, normal values in this range may be particularly
suspect; and a statement needs to be included in the interpretation stating so.
The signicant 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 specic 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 signicantly different values that may have different implications
with respect to risk. For example, a 5-foot, 9-inch 50-yearold 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

1/21/2008 10:19:57 AM

Chapter 3 Pulmonary Physiologic Testing

individual of similar age, height and weight, suggesting a


potentially excessive risk. On the other hand, false reassurance 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 specic normal equations cited when translating prognostic
results from literature dening risk assessment in other
potentially high-risk populations.

Determination of Normal Range


The 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 interpretation scheme, has been criticized as being statistically
unsound.14 Recent guidelines suggest the assessment of the
condence 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 condence interval
approach in middle-aged individuals of typical height.
However, even adhering to the statistically more sound condence 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
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 percentile or 95% condence 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.

Ch003-F06861.indd 29

29

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 Values


Subjects 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-specic 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 socioeconomic factors and body mass index may contribute. To avoid
these errors, race- and ethnic-specic reference equations are
used whenever possible and indicated in the report.3 Spirometric reference values from the National Health and Nutrition Examination Survey (NHANES III),18 the recommended
reference set of the 2005 ATS-ERS guidelines for interpretation of PFTs, provide different reference equations for male
and female Americans of European-American, AfricanAmerican, and Mexican-American populations.
An alternative to race-specic equations is to use adjustments 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 intermediate 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 Amputation
With 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 Values


The 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

1/21/2008 10:19:58 AM

30

Section 1 Introduction

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 decreasing through adolescence and beyond as lung elastic recoil
declines.

Patterns of Abnormality
Figure 3-9 offers a simplied algorithm for classifying PFT
patterns derived from the 2005 ATS-ERS standards.3

Obstructive Pattern
The 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

FEV1/VC
LLN

Yes

No

VC LLN

VC LLN

Yes

No

No
Yes

TLC LLN

Yes

TLC LLN
Yes

No
Normal

Restriction

DLCO LLN

DLCO LLN

Yes

Yes

No
PV
disorders

Normal

Obstruction

No

CW and NM
disorders

No

ILD
pneumonitis

Mixed defect

DLCO LLN
Yes

No

Asthma
CB

Emphysema

FIGURE 3-9 Interpretation chart. Simplied 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.)

of pulmonary function tests, an obstructive defect is dened


by an FEV1/VC ratio below the 5th percentile of the predicted 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 dened 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 airow
obstruction.
Other guidelines have chosen to dene 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 Education 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 discourages the use of a xed FEV1/FVC ratio to dene 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 reective
of age-related disease than the common presence of coronary 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 predicted, the low ratio may be a normal variant.3,15 In these
cases, the lung volume measurements can be helpful in identifying the presence of hyperination associated with obstructive patterns.
Recently, the forced expiratory volume in 6 seconds (FEV6)
has been proposed as an acceptable surrogate to the FVC for

5
Flow (L/second)

c
Volume (L)

4
c
3
b
2

4
3

a
1

3
4
5
Time (seconds)

4
5
Volume (L)

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

Ch003-F06861.indd 30

1/21/2008 10:19:58 AM

Chapter 3 Pulmonary Physiologic Testing

the assessment of airow obstruction because serial measurements of FVC requiring repeated forceful exhalations to RV
can be difcult 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 provided 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 dened by
FEV1/FVC was 95.0% and the specicity 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 denition of the end of test point, and less physical
demand on the subject.

Restrictive Pattern
A restrictive ventilatory defect is dened as a reduction in
TLC below the 5th percentile of the predicted value, accompanied 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 conrm 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 hyperination 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 specic.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 Defects


This pattern is dened 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 Classication of Patterns
The just-stated approach to classication 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 reecting 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% (<65% predicted) as minimal airow
obstruction in a subject with normal or borderline low values

Ch003-F06861.indd 31

31

of FEV1/VC and FEV1.3 It is no longer unacceptable, however,


to use FEF25-75% as an indicator of small airways disease
because this parameter can be affected by any pathologic
process resulting in airow obstruction.
In the setting of upper airway obstruction, typically the
FEV1, FVC, and VC are normal but peak expiratory ow
(PEF) may be reduced. Some specic measurements are
helpful in identifying upper airway obstruction (UAO). These
include an FEF50%/FIF50% (forced inspiratory ow at 50% of
FVC) ratio greater than 1 in the diagnosis of extrathoracic
UAO (normally the mid-inspiratory ow is higher than the
mid-expiratory ow) and a PEF/FEV1 ratio less than 8 in
intrathoracic UAO and xed UAO. However, assessing the
overall shape of the FVL (see later) is currently the best
method to identify these disorders.

Use of Flow-Volume Loops


Although visual appearance of FVLs often provides interesting academic insights into the subpatterns of disease presentation, their clinical utility beyond quantitative spirometric
assessment is largely unproven beyond their value in quality
assessment described earlier (see Fig. 3-3) and in the assessment of patterns of upper airway obstruction (Figs. 3-11
and 3-12)
Although uncommon, a high index of suspicion must be
maintained for the FVL patterns seen in UAO, dened as
obstruction in airow in regions originating from the hypopharynx to the tracheal bifurcation at the main carina. The
range of mechanisms associated with patterns of UAO
includes extrinsic compression (e.g., goiter or mediastinal
masses), intrinsic structural narrowing (e.g., tracheal stenosis
or tumor), and functional disorders of airway tone (e.g., vocal
cord dysfunction syndrome or functional stridor).
In contrast to obstructive diseases of the lower airways
such as asthma or COPD, which demonstrate a characteristic
scooped upward concavity (National Asthma Education,
1997),22-26,28 UAO causes a distinct attening of the inspiratory and/or expiratory limb of the FVL.
When the obstruction is xed, both inspiratory and expiratory limbs have a plateau-like attening. Neck position can
affect the observed pattern and severity of UAO with thyroid
enlargement. Neck exion worsens UAO as the thyroid slides
into the root of the neck/upper thorax (thyroid cork effect),
whereas neck extension reduces the degree of airow
obstruction.
Other upper airway lesions are variable in severity as
transmural pressures across the airway vary from inspiration
to expiration. When the obstruction is above the suprasternal
notch (variable extrathoracic UAO), these lesions demonstrate attened inspiratory limbs but relatively normal expiratory loops as the negative intraluminal pressure during
inspiration accentuates the narrowing (see Fig. 3-11). Thyroid
masses without retrosternal extension may show a typical
variable extrathoracic UAO pattern.
When the UAO is within the thoracic cavity, below the
suprasternal notch (variable intrathoracic UAO), the obstruction worsens on expiration because of compressive transmural
forces, whereas the negative extraluminal pressures associ-

1/21/2008 10:19:58 AM

32

Section 1 Introduction

identied in patients with neuromuscular disease (due to


weak upper airway muscles, particularly in extrapyramidal
disorders). The uttering is likely due to vibration of redundant 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.

14
12
10
Flow (L/s)

8
6
4
2

2
4

Rating of Severity

A
Expiration

Ptr > Patm

4
5
6
Volume (L)

Inspiration

Ptr < Patm

B
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 airow. 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.)

ated with inspiration result in more normal-appearing inspiratory loops (see Fig. 3-12).
Because diseases causing UAO patterns are uncommon,
many suggestive loops will be due to poor effort or can represent a normal variant. Such poor effort is generally associated with lack of repeatability, whereas true abnormalities are
repeatable.
High-frequency utter waves (sawtoothing) are sometimes 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 specic to that condition. Subsequently, it was also

Ch003-F06861.indd 32

Once the pattern of abnormalities is dened (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 hyperination (RV, TLC) or its indirect effects (reduced IC or increased IC/TLC) are independently associated with symptoms and may further complement
other physiologic measures in assessing severity in COPD,
although specic categories based on these parameters have
not been described.

Bronchodilator Response
ATS-ERS criteria for dening bronchodilator response considers a signicant 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 conrming the presence of a xed obstructive impairment. This testing, however,
is neither highly sensitive nor specic in distinguishing asthma
from COPD, does not represent a xed characteristic in an
individual patient (because reversibility status commonly

1/21/2008 10:19:58 AM

10

10

4
Flow (L/s)

Flow (L/s)

Chapter 3 Pulmonary Physiologic Testing

Volume (L)
a
Expiration

Ptr < Ppl

Volume (L)
b

33

FIGURE 3-12 A, Left (a), Variable intrathoracic UAO in this owvolume loop was caused by a rare granular cell tumor of the distal
trachea. Because the patient presented with wheezing, asthma
was suspected. The plateau and abrupt concave-down shoulder at
the right end are typical and contrast to the scooped-upward
concavity typical of COPD or asthma. The small squeak of a peak
ow before the plateau is sometimes seen and does not rule out
UAO if a plateau of ow is present. Right (b), A normal ow-volume
loop is shown after tumor resection. B, Variable intrathoracic UAO.
The transmural pressure gradient during expiration results in
compression of the intrathoracic trachea, as it does in the lower
airways in asthma and COPD. This narrowing in the trachea results
in a ow ceiling (plateau) during expiration. During inspiration, the
gradient across the tracheal wall distends the airway and ow
limitation at this site does not occur. (MODIFIED FROM CLIN CHEST
MED 15:35-53, 1994; ADAPTED FROM AM J MED 61:85, 1976.)

Inspiration

Ptr > Ppl

B
changes from month to month), and is not fully reective of
the clinical utility of a given inhaled agent.29,30 Pre- and postbronchodilator lung volume testing may demonstrate signicant decreases in hyperination (reduced FRC, RV) such that
signicant improvement in ow at the same lung volume,
associated with symptomatic improvements, may be observed
despite an unchanged FEV1 and FVC.31 Quantitative comparison of ow at the same lung volumes may be a method
of integrating these concepts and is termed isovolume ow
assessment.
A less well-accepted test of bronchodilator responsiveness
is improvement in ow at low lung volumes such as FEF25-75%.
Because the midow section is always dened by the VC in
which it resides, comparisons before and after use of a bronchodilator need to be adjusted to reect ow through the
same range of volumes (isoFEF25-75%), rather than from an
unadjusted FEF25-75%. Improvement in isoFEF25-75% of 35% or
more is suggestive of bronchodilator responsiveness when
taken from a study with excellent repeatability.

Assessing Signicant Change


in Lung Function Over Time
Repeated measurements may change for technical, statistical,
or biologic reasons. The FEV1 is the most tightly repeatable
PFT value and the best at tracking changes in both obstructive and restrictive disease. For short-term follow-up, differences in FEV1 above 12% and 200 mL are signicant and not

Ch003-F06861.indd 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

Rating

ATS/ERS
FEV1 (%)

GOLD
FEV1 (%)

Predicted
DLCO* (%)

Mild

>70

>79
(FEV1/FVC <0.7)

>60 and <LLN

Moderate

60-69

50-79

40-60

<40

Moderately severe

50-59

Severe

35-49

30-49

Very severe

<34

<30

*The rating of severity is appropriate to use after the test has been
determined to be abnormal based on a FEV1, VC, FEV1/VC, TLC, or
DLCO outside the normal range. Rating of severity of obstruction or
restriction is based on the FEV1.
ATS, American Thoracic Society; COPD, chronic obstructive pulmonary disease; DLCO, diffusing capacity; ERS, European Respiratory
Society; FEV1, volume exhaled in the rst second; LLN, lower limit of
normal.
Modied from Eur Respir J 26:948968, 2005; and www.goldcopd.org.

coincidentally the same value used to determine a signicant


intra-session bronchodilator effect.3 For year-to-year assessment, signicant changes ideally exceed 15%. Other parameters including VC, IC, TLC, and DLCO can be useful for
tracking change in COPD or interstitial lung disease. For

1/21/2008 10:19:58 AM

34

Section 1 Introduction

DLCO, signicant year-to-year changes of 15% or more are


likely meaningful. For idiopathic pulmonary brosis, it has
been suggested that a signicant 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 integrating the clinical scenario. Stable PFTs in a disease expected to
be progressive could be interpreted as a sign of effectiveness
of therapy. Lack of signicant improvement in a disease
expected to respond well to medication might be interpreted
as a failure of therapy. A signicant change in PFT measurements 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 Specic


Disease Classication
True Restrictive Disorders
These conditions include the intraparenchymal disorders
(interstitial and inltrative 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, dened by a low FVC and an FEV1/
FVC ratio greater than 70%, was found to have a sensitivity
of 93% but a specicity 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
conrmation by full lung volume measurements. A more cautious term for such spirometric patterns when full lung
volumes have not been measured is a nonspecic defect.

Neuromuscular Disease
These patients generally have a normal lung and chest wall
but weakness of the inspiratory muscles (mainly the diaphragm) and the expiratory muscles (mainly the abdominal
muscles), which limits inspiratory and expiratory deviation
from the resting lung volume (FRC). Consequently, the characteristic abnormality is a reduction in VC caused by reduction 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 restrictive disorders.
Patients with isolated or disproportionate bilateral diaphragmatic weakness or paralysis show a marked fall in VC
in the supine compared with the erect posture. This reects
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 associated with severe diaphragmatic weakness, and the postural
fall may exceed 50% in some subjects.

Ch003-F06861.indd 34

Although the MIP and MEP are the more specic 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 progression from moderate to severe respiratory muscle weakness.
The rate of decline in VC predicts survival in both amyotrophic 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 Asthma
Patients with obesity or asthma may have spirometric ndings that may be confused with those associated with true
restrictive disorders. FVC may be low with a normal or elevated 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 midexpiratory ow (FEF25-75%).35
Clues to distinguish a pseudorestrictive pattern in asthma
from true restriction and from the pseudorestriction of
obesity include the following:

Signicant 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, hyperination on lung volume measurements, and scooped-out FVL indicate that the true disorder
is obstructive.

Diseases With Mixed Obstructive


and Restrictive Defects
Diffuse interstitial or inltrative lung disease typically causes
restrictive patterns with normal or high FEV1/FVC and
reduced lung volumes (TLC, FRC, RV). Obstructive ventilatory defects can be seen in traditionally restrictive processes
such as sarcoidosis, rheumatoid lung disease, and advanced
idiopathic pulmonary brosis. This may be due to granulomatous airways disease (e.g., sarcoidosis), bronchiolitis (e.g.,
rheumatoid lung), or airway distortion from severe parenchy-

1/21/2008 10:19:59 AM

Chapter 3 Pulmonary Physiologic Testing

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 parenchyma in the bronchiectatic lung segments. Certain diffuse
inltrative diseases (e.g., eosinophilic granuloma and lymphangioleiomyomatosis) are typically associated with airow
obstruction and increased volumes.
Although bronchiolitis is an airway disease, proliferative
bronchiolitis, such as bronchiolitis obliterans organizing pneumonia, 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
hyperination.

Disease Processes Causing Abnormalities


of Diffusing Capacity
The 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 brosis, 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, Pneumocystis 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 elevated values.38
DLCO can be increased by conditions that lead to recruitment of the pulmonary vascular bed and an increase in capillary blood volume (exercise, mild congestive heart failure,
left-to-right shunt, asthma) or by an increased amount of
hemoglobin, which binds CO (pulmonary hemorrhage, erythrocytosis). 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 inspiratory VC against high airway resistance before performing the
breath-hold.

Cardiac Effects on PFTs


The 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

Ch003-F06861.indd 35

35

pulmonary congestion. In mild stages, with vascular congestion but without frank pulmonary edema, the increased capillary 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 difcult 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.

Bronchoprovocation
FEV1 and PEF rate are good measures of asthma severity and
measure the degree of airow obstruction. A related but distinct aspect of asthma is the degree of twitchiness of the
airways, known as airway hyperresponsiveness. This tendency
to bronchoconstriction can be assessed for specic antigens,
although it is more common to assess nonspecic hyperresponsiveness 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 methacholine is most frequently used.

Methacholine Challenge Testing


Clinically, 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 frequently 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 concentration. 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 considered positive shifts to higher concentrations when the pretest
likelihood of asthma is higher. Conversely, a lower concentration 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 plethysmograph to measure airways resistance (Raw) and its

1/21/2008 10:19:59 AM

36

Section 1 Introduction

reciprocal, conductance (Gaw). This is usually expressed as


specic 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 variability in this measurement than for FEV1.
Most consider bronchoprovocation highly sensitive for
asthma but nonspecic. Consequently, a negative test is a
strong argument against the diagnosis of asthma. Falsenegative ndings can be due to currently inactive or adequately 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 Bronchoprovocation
Assessment for exercise-induced bronchospasm can be performed as an add-on to CPET or as a separate diagnostic
maneuver. Testing for EIA in the laboratory is only moderately 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 bronchospasm, 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 bronchoprovocation 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 Dyspnea
Cardiopulmonary exercise testing can be useful in documenting 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, pulmonary angiography, lung biopsy, or muscle biopsy or indicate specic 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 determinations can direct therapy to the appropriate organ system.

Assessment of Intervention
Cardiopulmonary 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 specic physiologic changes
than resting testing but also allows assessment of the integrated 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

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.

NORMAL RESPONSE

VO2 max %

71%

HR %pred

95%

VE-max/MVV

0.62

AT % VO2 pred

50%

O2 pulse

92

BE

PCO2

34

VD/VT

0.21

180

100
HR 1/min

98%

140

60
100

20
60
1000

Ch003-F06861.indd 36

VE L/min

FEV1 %pred

2000

3000

VO2 mL/min

1/21/2008 10:19:59 AM

Chapter 3 Pulmonary Physiologic Testing

FIGURE 3-13, contd

PURE CARDIOVASCULAR LIMITATION

VO2 max %

66%

HR %pred

102%

VE-max/MVV

0.47

AT % VO2 pred

39%

O2 pulse

58

BE

PCO2

32

VD/VT

0.24

180

100
140
HR 1/min

87%

VE L/min

FEV1 %pred

37

60
100

20
60
1000

2000

3000

VO2 mL/min
PURE VENTILATORY LIMITATION
47%

VO2 max %

62%

HR %pred

77%

VE-max/MVV

0.92
NA

O2 pulse

81

BE

PCO2

48

VD/VT

0.47

100
140

60
100

VE L/min

AT % VO2 pred

180

HR 1/min

FEV1 %pred

20
60
1000

2000

3000

VO2 mL/min

PULMONARY VASCULAR DISEASE

VO2 max %

72%

HR %pred

98%

VE-max/MVV

0.53

AT % VO2 pred

36%

O2 pulse

62

BE

PCO2

26

VD/VT

0.42

180

100
140
HR 1/min

97%

60
100

20
60
1000

Ch003-F06861.indd 37

VE L/min

FEV1 %pred

2000

3000

VO2 mL/min

1/21/2008 10:19:59 AM

38

Section 1 Introduction

rates, lower VD/VT, and increased IC associated with less


dynamic hyperination; however, an earlier-onset lactic acidosis and elevated heart rate/oxygen consumption relationship due to simultaneous excision of the pulmonary vascular
bed may balance the benecial pulmonary. mechanical effects
and result in no change or deterioration in VO2max 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 PROGNOSIS
Measurements of maximal oxygen consumption are predictive of survival in individuals with cystic brosis, congestive
heart
failure, and COPD.50 Patients with cystic brosis with
.
VO2peak less than 59% predicted were more than three times
as likely to die as those with values greater than 82% of predicted, whereas measures of resting pulmonary function did
not independently correlate with survival.51 Individuals with
cardiomyopathy
awaiting heart transplantation who have
.
VO2peak greater than 14 mL/min/kg demonstrate a 94% oneyear survival compared with 70% of those individuals with
52
values less than 14 mL/min/kg.
Based on these data, indi.
viduals with values for VO2peak less than 14 are prioritized
in consideration for heart transplantation.
The National Emphysema Treatment Trial stratied 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 (dened earlier) experienced a greater than 50% reduction in mortality rate if they had upper lobe dominant disease,
whereas patients in the high-exercise category were not
likely to experience a survival benet. The high-exercise
responders, however, still experienced improved exercise tolerance 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 VO2 measures can dene subgroups of
. patients at excessively high
risk for surgery, and higher VO2 measures dene subgroups
at acceptable risk despite traditionally unacceptable FEV1
levels.53-55

Disability Assessment
Although clear guidelines for determination of disability are
lacking, it is clear that resting pulmonary function measurements 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

Ch003-F06861.indd 38

different jobs57; the average energy requirement on the job


does not exceed 50% of an individuals maximal work
capacity.

Pulmonary Rehabilitation
The use of CPET before pulmonary rehabilitation is recommended to dene safety and determine exercise prescription.
CPET allows supervised observation of potential ischemia,
arrhythmia, and desaturation before training sessions.58-60

COMMENTS AND CONTROVERSIES


It is critical that thoracic surgeons understand clearly the measurement 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 measurement are discussed. The denitions of lung volume and capacities 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 discussion of normal reference values is included. Also of particular
help is the excellent review of patterns of abnormality. The text and
accompanying gures are excellent source materials for the practicing thoracic surgeon.
G. A. P.

KEY REFERENCES
American Thoracic Society: Single-breath carbon monoxide diffusing
capacity. Recommendations for a standard technique; 1995 update.
Am J Respir Crit Care Med 152(6 pt 1):2185-2198, 1995.
American Thoracic Society/American College of Chest Physicians:
ATS/ACCP Statement on cardiopulmonary exercise testing. Am J
Respir Crit Care Med 167:211-277, 2003.
Crapo RO, Casaburi R, Coodes AL, et al: Guideline for methacholine
and exercise challenge testing1999. This ofcial statement of the
American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 161:309-329, 2000.
Miller MR, Hankinson J, Brusasco V, et al; ATS/ERS Task Force:
Standardisation of spirometry. Eur Respir J 26:319-338, 2005a.
Miller M, Crapo R, Hankinson J, et al; ATS/ERS Task Force: General
considerations for lung function testing. ATS/ERS Task Force. Eur
Respir J 26:153-161, 2005b.

1/21/2008 10:20:00 AM