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Pulmonary Function Testing

Adam Anderson and Adrian Shifren

GENERAL PRINCIPLES
• Pulmonary function tests (PFTs) are an integral part of a pulmonary evaluation and
management.
• PFTs can be divided into spirometry (measurement of air movement in and out of the
lungs), diffusing capacity (measure of gas exchange within the lungs), and
plethysmography (measurement of lung volumes).
• The availability of user-friendly pulmonary function testing devices has resulted in
widespread use of on-site PFTs by community physicians and an increased need for formal
training in collecting and interpreting valid pulmonary function measurements.
• PFTs are best interpreted in relation to an individual’s clinical presentation and not in
isolation. All parts of the PFTs should be used when evaluating a patient.
• It is important to remember that PFTs do not make pathologic diagnoses such as
emphysema or pulmonary fibrosis. They provide physiologic measurements identifying
ventilatory defects and, in doing so, support the existence of the relevant disease process
and aid in the evaluation of its treatment.
• This text assists with evaluation of basic spirometry, diffusing capacity, and lung volumes
and will allow the reader to identify common ventilatory defects using the data provided
by PFTs.

NORMAL VALUES AND REFERENCE RANGES

• The results of PFTs are interpreted by comparing them to reference values representing
normal healthy subjects.
• These normal or predicted values take into account many variables, most importantly
age, height, gender, race/ethnicity, and to a lesser extent, weight.
• However, they neglect other influencing variables that may have effects, including air
pollution, socioeconomic status, and others.

Percent Predicted Method

• Traditionally, but without scientific basis, pulmonary function labs have arbitrarily set
normal ranges for each predicted value.
• The lower and upper limits of normal for each predicted value are set as 80% and 120% of
the predicted value, respectively.
• The measured values for each pulmonary function variable are compared with the
 predicted values of each variable and expressed as “percent of predicted.”
• Measured values that fall within the 80–120% range of predicted values are considered
normal.
• This method is used in this text because it permits easy instruction and is still in widespread
use.

Fifth Percentile Method

• An alternative method for defining normal range of each predicted (normal) value uses a
percentile-based approach.
• Using this method, measured values less than the 5th percentile or greater than the 95th
percentile within a healthy population are considered abnormal.
• The percentile method can lead to more precise diagnoses of chronic obstructive pulmonary
disease (COPD), especially in the elderly.1 The percent predicted method may over-
diagnose COPD in elderly patients.2

STANDARDIZATION OF PULMONARY FUNCTION TESTS

• To obtain useful information from PFTs, the adequacy of both the testing equipment and
the test results needs to be scrutinized.
• The American Thoracic Society (ATS) publishes guidelines for the standardization of
spirometry, including recommendations on equipment calibration, validation of results,
measurement of parameters, and acceptability and reproducibility criteria for the data
obtained.3,4
• Because most PFTs are obtained from dedicated PFT labs, this text describes the
standardized criteria for interpretation of PFT data and excludes details on equipment setup
and testing techniques.
• Only when all the acceptability and reproducibility criteria are met can PFTs be interpreted
with confidence.
• If acceptability and reproducibility criteria are not met, further testing needs to be
performed to assess maximum function.
• Up to eight patient efforts may be performed; after this, patient fatigue affects the data
obtained.
• The best results are always used for interpretation.

Acceptability Criteria
PFTs should initially be assessed for acceptability that is best determined by studying the
flow-volume loops. Acceptability criteria for PFTs include the following:
• Freedom from artifacts (coughing, glottic closure, early termination leak, variable effort)
• Good starts (i.e., the initial portion of the curve that is most dependent on patient effort is
free from artifact)
• Satisfactory expiratory time (at least 6 seconds of expiration on the volume–time curve, or
at least 1-second plateau in the volume–time curve)

Reproducibility Criteria
Once the minimum of three acceptable flow-volume loops has been obtained, the
reproducibility of the PFTs should be assessed. Reproducibility criteria for PFTs include the
following:
• The two largest forced vital capacity (FVC) measurements should be within 0.2 L of each
other.
• The two largest forced expiratory volumes in 1 second (FEV1) measurements should be
within 0.2 L of each other.

NORMAL PULMONARY FUNCTION TESTS

Flow-Volume Loops
• Normal PFTs are defined by a normal-shaped flow-volume loop (Fig. 3-1).5
• The flow-volume loop is the plot of the FVC maneuver.

FIGURE 3-1. Normal flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of Pulmonary Function Tests.
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical Education and Research.)

• The FVC maneuver involves the patient taking a maximum inspiration followed by a
maximum and forceful expiration.
• The flow-volume loop portion of pulmonary function testing is also known as spirometry.
• The expiratory limb of a normal flow-volume loop has a rapid peak and a gradual decline
in flow back to zero.
• The inspiratory limb should have a rounded shape.

FEV1 and FVC

• Normal pulmonary function is also defined by the measured values for the FVC and the
FEV1.
• FVC is defined as the maximum volume of air that is forcefully exhaled after a maximum
inspiration.
• FEV1 is defined as the maximum volume of air exhaled during the first second of the FVC.
• The measured values for FEV1 and FVC are compared to the predicted values for FEV1 and
FVC as a percent of predicted. Values of 80–120% are considered normal.

Lung Volumes
• Lung volumes are measured separately from the flow-volume loop.
• Like the FEV1 and FVC, measured lung volumes are compared to the predicted values for
that volume as a percent predicted.
• Lung volumes between 80% and 120% are considered normal.
• The most important lung volumes for this discussion are total lung capacity (TLC), residual
volume (RV), and slow vital capacity (SVC).
TLC is defined as the volume of air in the lung after complete maximal inspiration and a
value of 80–120% of predicted is normal.
RV is defined as the volume of air left in the lungs after complete maximal expiration and
a value of 80–120% of predicted is normal.
SVC is defined as the maximal volume of air that can be exhaled with normal effort after
a maximum inspiration. (It is similar to the FVC except performed without full force.) A
value of 80–120% of predicted is normal.

EVALUATING PULMONARY FUNCTION TEST PATTERNS

There are normal, obstructive, and restrictive patterns observed on PFTs, which will be
discussed in detail. The following algorithm will allow for characterization of the disease
pattern (Fig. 3-2).6,7

OBSTRUCTIVE VENTILATORY DEFECTS

• An obstructive ventilatory defect (OVD) exists when there is a disproportionate decrease in
the FEV1 when compared to the FVC. An FEV1:FVC ratio of <70% defines an OVD.
• The FVC may be reduced in an OVD, but the FEV1 is always reduced to an even greater
degree.
• The ATS cautions against diagnosing an OVD in individuals who have a decreased
FEV1:FVC ratio but normal measured FEV1 and FVC, because this pattern can on occasion
be seen in healthy subjects.
• OVDs indicate airflow limitation and imply airway narrowing.
• In emphysema, for example, the narrowing is believed to be the result of decreased elastic
support of smaller airways owing to alveolar septal destruction, whereas in chronic
bronchitis, mucosal inflammation and excess mucus production are the etiologies.
• Once the diagnosis of an OVD has been made, the defect needs to be fully characterized by
performing the following:
Quantifying the severity of the OVD
Assessing the reversibility of the obstruction
Determining whether there is hyperinflation
Determining whether there is air trapping

Quantifying an Obstructive Ventilatory Defect

Quantifying the severity of the OVD is done by comparing the measured FEV1 to the
predicted FEV1 as a percent (Table 3-1).

Assessing for Bronchodilator Reversibility

 • Assessing for reversibility of an obstruction requires spirometry be performed both before
and after bronchodilator administration.
• An increase in the postbronchodilator FEV1 or FVC (calculated from prebronchodilator
values) of both ≥12% and ≥200 mL defines a positive bronchodilator response and
indicates reversibility of an airway obstruction.
• Thus, reversibility is said to be present when, compared with prebronchodilator values:
Postbronchodilator FEV1 improves by both 12% and 200 mL, OR
Postbronchodilator FVC improves by both 12% and 200 mL
• These criteria are best applied when active therapy is not present (e.g., no albuterol for 4
hours).
• The lack of reversibility during a PFT does not prohibit a clinical response to
bronchodilator therapy.
• Although asthma is typically a reversible OVD, bronchodilator responsiveness during a PFT
is not pathognomonic for asthma.

FIGURE 3-2. Evaluation of pulmonary function tests. DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity;
TLC, total lung capacity. (Data from Pellegrino R, Viegi G, Brusasco V, et al. Interpretive strategies for lung function tests. Eur
Respir J. 2005;26:948–68; and Al-Ashkar F, Mehra R, Mazzone PJ, et al. Interpreting pulmonary function tests: recognize the
pattern and the diagnosis will follow. Cleve Clin J Med. 2003;70(10):866, 868, 871–73.)

TABLE 3-1 QUANTIFYING AND CLASSIFYING THE SEVERITY OF AN OBSTRUCTIVE

VENTILATOR DEFECT
Determining If Hyperinflation Is Present
• Hyperinflation denotes that at maximum inspiration or expiration the lungs are at a
greater volume than is expected for an individual. In physiologic terms, the individual’s
TLC or RV is increased.
• The presence of hyperinflation is determined by comparing the measured TLC or RV to
the predicted TLC or RV as a percent:
TLC >120% of predicted, or
RV >120% of predicted
• Some sources consider hyperinflation to be present only when the TLC >120% of
predicted, and air trapping to be present when the RV >120% of predicted.

Determining If Air Trapping Is Present

• Air trapping denotes that during forced (rapid) expiration, there is dynamic collapse of
airways with resultant incomplete exhalation of air compared with nonforced (slow)
expiration. In physiologic terms, the individual’s FVC is smaller than the SVC.
• Air trapping occurs because forced expiration causes worsening of airway obstruction as a
result of higher positive intrathoracic pressures.
• An increase in the SVC by both ≥12% and ≥200 mL compared with the FVC indicates air
trapping. SVC ê FVC by both 12% and 200 mL.
• Some sources consider air trapping to be present when the RV >120% of predicted.

The Flow-Volume Loop in Obstructive Ventilatory Defects

• OVDs change the shape of the flow-volume curve. The expiratory curve still has a rapid
initial peak, but the terminal portions of the expiratory flow drop progressively with
worsening obstruction.
• As a result, the expiratory limb of the curve takes on a progressively increasing concavity.
Eventually, there is also a decrease in the peak expiratory flow at the initial portion of the
curve.
• In severe disease, there is an initial rapid but reduced peak followed by a precipitous drop
in flow and a very gradual taper of the flow to zero (Fig. 3-3).5
• Where lung volumes are measured the curve will also shift leftward, indicating that all lung
volumes have increased, consistent with air trapping and hyperinflation.

UPPER AIRWAY OBSTRUCTION

• The OVDs discussed so far all represent obstruction at the level of smaller, more distal
airways. Obstruction of the larger, more central airways (trachea and major bronchi)
presents differently and is most easily identified on inspection of the inspiratory and
expiratory limbs of the flow-volume loop.
FIGURE 3-3. Obstructive lung disease flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of Pulmonary
Function Tests. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical Education and
Research.)

• Three forms of upper airway obstruction can be discerned:

Fixed obstruction
Variable intrathoracic obstruction
Variable extrathoracic obstruction

Fixed Upper Airway Obstruction

• When a central airway contains a fixed obstruction, the cross-sectional area of the
obstructed airway does not change throughout the respiratory cycle (hence its
characterization as fixed).
• The obstruction is present during both inspiration and expiration, and both limbs of the
flow-volume loop are almost equally affected.
• There is characteristic truncation of both the inspiratory and expiratory limbs with the
resulting “box” shape on the flow-volume loop (Fig. 3-4).5

Variable Upper Airway Obstruction

• When an airway contains a variable obstruction, manifestation of the obstruction is
dependent on both the location of the obstruction (within or external to the thorax) and the
phase of the respiratory cycle (inspiration or expiration).
• Changes in the cross-sectional area of the obstructed airway vary with both inspiration and
expiration and intra- or extrathoracic location of the obstructing lesion.
In variable intrathoracic obstruction, the expiratory limb is primarily affected.
During forced expiration, pleural pressure exceeds the intrathoracic airway pressure. As a
result, the airway narrows, and the obstruction worsens. During forced inspiration, the
pressure relationships are reversed, and the obstruction is relieved. Thus, only the
expiratory limb is truncated (Fig. 3-5).5
In variable extrathoracic obstruction, the inspiratory limb is primarily affected.
FIGURE 3-4. Fixed upper airway obstruction flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of
Pulmonary Function Tests. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical
Education and Research.)

During forced inspiration, atmospheric pressure exceeds the extrathoracic tracheal

pressure. As a result, the airway collapses, and the obstruction worsens. During forced
expiration, the pressure relationships are reversed, and the obstruction is relieved. Thus,
only the inspiratory limb is truncated (Fig. 3-6).5

FIGURE 3-5. Variable intrathoracic obstruction flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of
Pulmonary Function Tests. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical
Education and Research.)

FIGURE 3-6. Variable extrathoracic obstruction flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of
Pulmonary Function Tests. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical
Education and Research.)

RESTRICTIVE VENTILATORY DEFECTS

• A restrictive ventilatory defect (RVD) exists when there is a reduction of maximum lung
inflation, manifested by a reduction in TLC. Therefore, a TLC <80% of predicted defines
an RVD.
• The presence of an RVD may be suspected using spirometry when the FVC is reduced in
proportion to the reduction in FEV1. In these cases, the FEV1:FVC ratio will be either
normal or increased.
• To diagnose an RVD definitively, however, lung volumes must be obtained to determine
the TLC.
• An RVD is not specific for any specific disease. In interstitial pulmonary fibrosis, the
restriction is the result of the fibrosis of the alveolar walls and “stiffening” of the lung
parenchyma. In muscular dystrophy, weakened diaphragmatic and thoracic muscles are the
etiologies.
• An RVD can also be caused by removal of lung tissue (lobectomy, pneumonectomy) as this
results in a decrease in the total lung volume (hence TLC) compared to that predicted for
the patient.
• Once the diagnosis of an RVD has been made, the defect needs to be quantified, which is
done using the FEV1 or the TLC percent predicted (Table 3-2).

The Flow-Volume Loop in Restrictive Ventilatory Defects

• The proportions of the flow-volume loop are essentially unchanged in RVDs.
• The curve is often narrowed and shifted to the right, reflecting the smaller lung volumes
associated with RVDs (Fig. 3-7).5
• Although peak expiratory flow is decreased, note that at each measured lung volume, flow
is often greater than in normal lungs.
• The features are only suggestive of an RVD; measurement of TLC must be performed to
make the diagnosis.

TABLE 3-2 SEVERITY OF RESTRICTIVE VENTILATORY DEFECT

DIFFUSING CAPACITY
• Diffusing capacity is often measured as part of a PFT. It is performed separately from
spirometry and lung volume measurement.
• It is a measure of the integrity of the alveolar-capillary membrane across which gas
 exchange takes place.
• The diffusing capacity is a nonspecific measurement and provides only a physiologic
assessment of the efficiency of gas exchange.
• Any disease affecting the pulmonary parenchyma or circulation can alter the diffusing
capacity.
• The gas used to measure diffusing capacity is carbon monoxide, and the diffusing capacity
is expressed as diffusing capacity of the lung for carbon monoxide (DLCO).
• The measured value is often adjusted to eliminate the effects of the hemoglobin
concentration, which may artificially increase (high hemoglobin concentration) or reduce
(low hemoglobin concentration) the DLCO.8 The adjusted value is expressed as the
adjusted DLCO (DLCOADJ). The adjusted value for DLCO is sometimes called the
corrected DLCO (DLCOC).

FIGURE 3-7. Restrictive lung disease flow-volume loop. (From Hyatt RE, Scanlon PD, Nakamura M. Interpretation of Pulmonary
Function Tests. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. © Mayo Foundation for Medical Education and
Research.)

• Calculation of the DLCOADJ is not mandatory but desirable.

• Measured values of DLCO and DLCOADJ are compared to predicted values as a percent (the
percentile method may also be used).
• Percent predicted values for DLCO between 70% and 120% are considered normal. Also
percent predicted values for DLCOADJ between 70% and 120% are considered normal.
• The reason for the wide range in normal DLCO and DLCOADJ is the large amount of
variability between different measurements in the same individual at any given time. Of
note the finding of normal PFTs with an isolated decrease in DLCO should raise a high
index of suspicion for pulmonary vascular disease.

OTHER PULMONARY FUNCTION TESTS

Maximal Voluntary Ventilation
• Maximal voluntary ventilation (MVV), reported in liters per minute, is defined as the
maximum amount of air that can be breathed in and out in 1 minute.
• For patient comfort, it is usually measured over 12 seconds and the value extrapolated to 1
minute.
• MVV is a very nonspecific measurement and can be reduced in either restrictive or
 obstructive disorders.
• MVV is often used to assess patient’s respiratory musculature prior to surgery to help
predict postoperative pulmonary complications.
• MVV is very effort dependent and requires good patient instruction.
• It is also a reflection of lung volume changes, lung–thorax compliance, and airway
resistance. Therefore, MVV may be a less than accurate predictor of respiratory strength
and endurance.
• Average values for males and females are 140–180 L/min and 80–120 L/min, respectively.
• However, interpretation is more complicated because MVV is proportional to FEV1 and will
decrease when FEV1 is reduced.
• The following predictive equation is used to determine predicted MVV in the setting of a
reduced FEV1. Predicted MVV = FEV1 × 40. Some sources use FEV1 × 35 to
calculate predicted MVV. Other more complex formulas also exist.
• In the setting of a reduced FEV1, the predicted MVV may be reduced proportionately to the
reduction in FEV1, it may be reduced in excess of the reduced FEV1, or it may be reduced
to a lesser degree than predicted by the reduction in FEV1.

Methacholine Challenge Testing

• Asthma is defined as a reversible obstructive airway disease. Therefore, in individuals
suspected of having asthma, PFTs may appear normal, without evidence of obstruction.
• In individuals where PFTs are normal but asthma is strongly suspected, bronchial
provocation testing is indicated to induce airway constriction and allow for the diagnosis
(and further management) of asthma.
• Other individuals who should be considered for bronchial provocation testing include those
with9:
Chronic cough
Wheezing
Intermittent dyspnea
Work place-related cough/wheezing/dyspnea
Exercise-associated cough/wheezing
• The methacholine challenge test is a nonspecific test of airway responsiveness. It allows for
a semiquantitative assessment of airway reactivity but gives no insight into the stimulus
responsible for the reactivity in an individual.

TABLE 3-3 METHACHOLINE DILUTION SCHEDULE

• The advantage of the test is that it has good reproducibility.
• The disadvantage is that multiple factors can affect the test, including the following:
Medications (bronchodilators, steroids, antihistamines, β-agonists, calcium-channel
blockers)
Respiratory infection
Exposure to sensitizers (allergens or chemicals)
• The test begins with the administration of a sterile saline aerosol followed by the
measurement of the FEV1 after 3–5 minutes (as a baseline).
• Increasing concentrations of methacholine diluted in sterile saline are then administered to
the patient at 5-minute intervals, and the FEV1 is measured 3–5 minutes after each increase
in concentration.
• The concentrations range from 0.003 to 16 mg/mL of methacholine in sterile saline and are
roughly doubled each time until either a positive response is obtained or a maximum
concentration is achieved (Table 3-3).
• A positive methacholine challenge is defined as a decrease in FEV1 from baseline of
>20% at a methacholine concentration of ≤8 mg/mL.
• The methacholine concentration resulting in a positive challenge is reported as the PC20
(provocative concentration causing a 20% fall in FEV1), for example, a decrease in FEV1
from baseline occurring at a methacholine concentration of 0.5 mg/mL is reported as a
PC20 = 0.5 mg/mL.
• A negative methacholine challenge occurs if there is no change from baseline, or
any decrease in FEV1 from baseline is <20% and a concentration of >8 mg/mL has
been reached.
• When patients undergoing bronchial provocation testing are on inhaled corticosteroids, a
decrease in FEV1 from baseline of >20% at a methacholine concentration of 16 mg/mL
may be considered a positive methacholine challenge test.10

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