Pruebas de Función Pulmonar Cecil

518 CHAPTER 79 Respiratory Testing and Function
of bronchoalveolar lavage fluid, obtained by bronchoscopy, can also provide

important insights into pulmonary disease.
SPIROMETRY
The simplest, most commonly performed pulmonary function test is spirom-
etry (Table 79-1).3 This test measures the forced vital capacity (FVC), which
is the amount of air that can be forcefully expelled from the lungs, beginning
79 at maximal inhalation (termed total lung capacity) and ending with the lungs
emptied to their minimal volume (residual volume). Many secondary measures
are derived from the FVC maneuver, including volume exhaled in a given
RESPIRATORY TESTING AND FUNCTION time, termed the forced expiratory volume (FEV), with a subscript indicating
the number of seconds during which this measurement is made (e.g., FEV1,
PAUL D. SCANLON FEV3). The ratio of the FEV1/FVC is the proportion of the total vital capacity
that can be expelled in the first second of a maximal expiratory effort; a low
FEV1/FVC ratio indicates obstructive lung disease, with a threshold of ≤70%
Pulmonary function testing has been used in the medical evaluation of patients indicative of an increased risk for future hospitalization or mortality owing to
with respiratory issues since Hutchinson’s 1846 demonstration that vital capac- chronic obstructive pulmonary disease.3b In addition, expiratory flow can be
ity, the largest volume of air that can be exhaled, is an important measure of measured at specific portions of exhaled vital capacity, termed forced expira-
health. Lung function is one of the most important predictors of all-cause tory flow (FEF), followed by a number to represent the percentage of the
mortality.1 Although environmental exposures,2 especially exposure to tobacco FVC at which the flow was measured (e.g., FEF75, FEF50, FEF25). Expiratory
smoke, and diseases are known to affect pulmonary function, genetic influ- flow can also be measured over a volume range (e.g., FEF25-75). Spirometry
ences also contribute. Pulmonary function is central to our understanding of results are reproducible within a test session and over time between test ses-
pulmonary disorders: many are classified as “obstructive” or “restrictive” dis- sions, thereby allowing comparisons over time for clinical evaluation and as
orders in acknowledgement of their pulmonary function pattern. Change or an important outcome in research studies.
stability of pulmonary function is a key outcome in many clinical trials of The data from a maximal exhalation is displayed with a flow-volume curve
respiratory medications. (Fig. 79-1A), which depicts exhaled flow at any given volume as a function
Measures of lung function include assessments of respiratory mechanics, of exhaled volume. The flow-volume curve has a unique shape for any indi-
for example, the volume of gas that is contained by the lung in various cir- vidual at any given time. It can reflect airway obstruction (Fig. 79-1B and C),
cumstances, the inspiratory and expiratory flow rates across the vital capacity, such as is seen in asthma (Chapter 81) and chronic obstructive lung disease
the pressures that can be generated by inspiratory and expiratory efforts, and (COPD; Chapter 82), or lung restriction (Fig. 79-1D and E), such as is seen
the resistance to airflow, as well as calculations of gas exchange. The analysis in many interstitial lung diseases (Chapter 86). A restrictive disorder may be
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CHAPTER 79 Respiratory Testing and Function

518.e3
ABSTRACT KEYWORDS
Pulmonary function testing (PFT) is key to the evaluation and treatment of pulmonary function testing
many disorders of the respiratory system and is central to the definition of cardiopulmonary exercise testing
obstructive and restrictive disorders. This chapter briefly summarizes methods bronchoalveolar lavage
for lung function testing, well illustrated with “real” flow volume curves and interpretation
guided by a detailed algorithm. Bronchoalveolar lavage also is succinctly obstruction
reviewed. Supplementary online materials include a more complete discussion restriction
of complex pulmonary function disorders (mixed, nonspecific, and complex nonspecific pattern
restrictive), the effects of obesity on PFTs, and a series of review questions. complex restriction

519
not part of routine spirometry, may be useful for patients in whom there is a
TABLE 79-1 PULMONARY FUNCTION TESTS suspicion of upper airway disease, such as a patient who has stridor, whose
MVV is reduced out of proportion to the FEV1, or has been referred by an
LUNG VOLUMES
otorhinolaryngologist.
TLC Total lung capacity (volume of gas in lungs at the end of maximal
inspiration) REFERENCE EQUATIONS
FRC Functional residual capacity (volume of gas in the lungs at Normal lung size varies from person to person as a function of height, age,
relaxation, when the inward pull of lungs is balanced by the sex, and ethnicity, Therefore, values obtained from pulmonary function testing
outward pull of the relaxed chest wall) are compared with those of normal individuals with similar characteristics.
RV Residual volume (FRC − ERV, volume of gas left in lungs after Results are expressed as a percentage of a reference value calculated with those
maximal exhalation) four factors. Normal values in African American individuals are about 12%
ERV Expiratory reserve volume (volume of gas expired between FRC lower than values from white persons of the same sex, age, and height. Normal
and RV) values are also about 6 to 15% lower in southern Asians. Inspiratory capacity
EXPIRATORY FLOW is also higher in people who live at higher altitudes.4 Genetic markers of ethnic
FEV1 Forced expiratory volume (in 1 second) ancestry are predictive of lung function and, in the future, might be used
FVC Forced vital capacity
instead of self-declared ethnicity to improve on traditional methods of adjust-
ing for racial or ethnic variation.
FEV1/FVC FEV1/FVC ratio (expressed as percentage)
DIFFUSING CAPACITY LUNG VOLUMES
Dlco Diffusing capacity of lungs for carbon monoxide The volume of air in the lung at any given time can be partitioned (Fig. 79-2).
ARTERIAL BLOOD GASES The air that remains in the lung after a maximal expiratory effort is the residual
volume. The amount of air in the lungs at the relaxation point, when muscle
Pao2 Partial pressure of oxygen in arterial blood
effort is minimized and the inward recoil of the lung is balanced by the outward
Paco2 Partial pressure of carbon dioxide in arterial blood recoil of the chest wall, is the functional residual capacity (FRC). The differ-
pH Negative log of hydrogen ion concentration ence between FRC and residual volume is the expiratory reserve volume. The
volume exhaled in a normal breath is the tidal volume. The volume that can
be inhaled above tidal volume is the inspiratory reserve volume.
indicated by a decreased FEV1 and FVC but a preserved or even an increased A series of capacities consist of the sum of two or more different volumes.
FEV1/FVC ratio. It also may demonstrate less common abnormalities, includ- FRC is the sum of expiratory reserve volume plus residual volume. Inspi-
ing variable extrathoracic (Fig. 79-1F) or intrathoracic (Fig. 79-1G) obstruc- ratory capacity is the sum of tidal volume plus inspiratory reserve volume.
tion, tracheal stenosis (Fig. 79-1H), or severe muscle weakness (Chapter 80; Vital capacity is the sum of tidal volume plus inspiratory reserve volume plus
Fig. 79-1I). expiratory reserve volume. Total lung capacity is the sum of residual volume
The FVC, FEV1, FEV1/FVC ratio, and shape of the flow-volume curves are plus expiratory reserve volume plus tidal volume plus inspiratory reserve
highly reproducible measures of lung function if the tested individual makes volume.
an expiratory effort above a certain, easy-to-obtain level in a pulmonary func- Three of the volumes (tidal volume, inspiratory reserve volume, expiratory
tion laboratory with modern spirometry equipment and trained staff. In the reserve volume) can be measured with a spirometer. Measurement of residual
absence of quality assurance, however, measurements of lung function are volume or any of the capacities that include it, so-called absolute lung volumes,
neither accurate nor reproducible; poor-quality pulmonary function testing requires more sophisticated methods, such as body plethysmography, the inert
results are biased to lower values, thereby giving an incorrect impression of gas dilution technique, or the nitrogen washout technique.
disease where none may exist. In some but not all cases, poor performance
is obvious from inspection of the flow-volume curve (Fig. 79-1L). One way Body Plethysmography
to assess a patient’s performance is to compare multiple efforts and to docu- Body plethysmography, the preferred method for measuring lung volumes, is
ment that the two best measures of both FVC and FEV1 are within 150 mL based on Boyle’s law: at a given temperature, the product of the pressure and
of each other, a standard that most people can meet without difficulty. Poor volume of a quantity of gas at one time will be equal to the product of the
performance should be noted by the interpreter to avoid erroneous diagnoses. pressure and volume of the gas at another time (P1 × V1 = P2 × V2). The
Spirometry is recommended for diagnosis of airflow obstruction in symp- process of measuring lung volume by plethysmography consists of panting
tomatic patients. It is not recommended as a screening test for asymptomatic against a closed shutter to compress and to rarify gas in the chest. The body
persons thought to be at risk for development of lung disease, such as current plethysmograph, a sealed box in which the patient sits, measures the changes
or former smokers, because an abnormal spirometry result has not been shown in lung volume during panting; pressure measured at the mouth represents
to improve the likelihood that such at-risk individuals will quit smoking. Fur- the pressure changes within the lung during these volume changes. A similar
thermore, a normal screening spirometry test result might be misinterpreted panting maneuver with the shutter open is used to calculate airway resistance.
as an indicator that smokers can continue smoking without risk. Nevertheless, Although body plethysmography is generally the most accurate method for
spirometry may be part of workplace respiratory health programs in at-risk measurement of lung volumes, particularly in patients with airway obstruction,
occupational settings. it can overestimate lung volumes if panting is too rapid. A plethysmographic
Spirometry is often performed before and after administration of an inhaled total lung capacity greater than 150% of the reference value should be viewed
bronchodilator, either a β-agonist (e.g., albuterol) or a muscarinic antagonist with suspicion.
(e.g., ipratropium) or both, especially if it shows changes consistent with airway
obstruction. Dosing may use two or four puffs from a metered dose inhaler Inert Gas Dilution Technique
or nebulized aerosols. The degree of improvement after bronchodilator admin- Lung volumes also can be measured by having the patient rebreathe from a
istration indicates the degree of airway reactivity, which is generally more in device containing a known volume and concentration of an inert gas (e.g.,
asthma (Chapter 81) and less in COPD (Chapter 82). Response to broncho- helium, neon, argon, or methane), which does not react with elements in the
dilators varies with dosage, is poorly repeatable from test to test, and is not a blood or tissues, until equilibrium is achieved. The final concentration of helium
good predictor of the clinical response to bronchodilator therapy in an indi- equals the initial helium concentration times the initial volume of the device
vidual patient. divided by the final volume of the lungs plus the device, adjusting for oxygen
consumption and carbon dioxide production during the test. The equation
OTHER TESTS OF VENTILATION can be solved for lung volume. This method underestimates lung volumes
Maximal voluntary ventilation (MVV) is an indication of the maximal ventila- when portions of the lung communicate poorly with the central airways, par-
tion a patient can perform, expressed in liters per minute. MVV estimates a ticularly in patients with emphysematous bullae.
person’s upper limit of ventilatory capacity. Reductions in MVV may be due
to inspiratory obstruction, muscle weakness, or poor performance. Because Nitrogen Washout Technique
MVV is effort dependent, it may be a better predictor of postoperative respira- The air that we breathe consists of approximately 21% oxygen, 1% argon,
tory complications (Chapter 405) than is FEV1. Inspiratory flows, which are 0.04% carbon dioxide, and a variable amount of water vapor. The remainder
Normal Moderate ObstructionÞ Severe Obstruction
12 10 12
Flow Volume Curve Flow Volume Curve
Maximal Expiratory Flow, liters/sec

Predicted Control Predicted
10 10
Control 8 Bronchodilator Best
2nd best
8 8 3rd best
6
6 6
4
4 4
2 2 2
0 0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 0 1 2 3 4 5 6
A Expired Volume, liters B Expired Volume, liters C Expired Volume, liters
Moderate Restriction Severe Restriction Variable Extrathoracic Obstruction

(Granulomatosis with polyangiitis)
10 10 10

Control Control Control

Bronchodilator 8 Control Insp
8 Bronchodilator 8
6
6 6 4
2
4 4
0
2 2 1 2 3 4 5
–2
0 0 –4
0 1 2 3 4 5 0 1 2 3 4 5
D Expired Volume, liters E Expired Volume, liters F Expired Volume, liters
Variable Intrathoracic Obstruction Fixed Obstruction Weakness

(Relapsing Polychondritis) (Tracheal Stenosis) (Myopathy)
10 10 10
8 Control Control Maximal Expiratory Flow, liters/sec Control

Bronchodilator
8 Control Insp
8
6 Bronchodilator Insp
6
4 6
4
2
2 4
0
2 3 4 5 0
–2
2
–4
1 3 4 5
–6 –2 0
0 1 2 3 4 5
G Expired Volume, liters H Expired Volume, liters I Expired Volume, liters
Normal with Prominent Sawtooth Pattern Poor Performance

“Tracheal Plateau”
12 12 12 0
Flow Volume Curve
Maximal Inspiratory Flow, liters/sec
Flow Volume Curve
Control PRED mayo FET

10 Challenge 10 10 PRED mayo 2
Control
Control 7.2
Post dilator
8 8 8 4
6 6 6
6
4 4 4 8
2 2 2 10
0 0 0 12
0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 8
J Expired Volume, liters K Expired Volume, liters L Expired Volume, liters
FIGURE 79-1. Common patterns of flow-volume curve. A, Normal. B, Moderate obstruction. C, Severe obstruction. D, Moderate restriction. E, Severe restriction. F, Variable extratho-
racic obstruction (granulomatosis with polyangiitis). G, Variable intrathoracic obstruction (relapsing polychondritis). H, Fixed obstruction (tracheal stenosis). I, Weak effort (myopathy).
J, Normal but with a prominent tracheal plateau. K, Sawtooth curve associated with obstructive sleep apnea. L, Poor quality maneuver with both delay in peak flow and cough within
the first second. Control = patient’s baseline performance; Insp = inspiration; Challenge = methacholine challenge.

521
TLC gas mixture is exhaled. The concentration of inert gas is used to calculate the
volume of the lungs (alveolar volume); the concentration of carbon mon-
oxide is used to calculate the absorption of carbon monoxide, expressed in
volume per minute per unit of pressure (mL/min per mm Hg). Methods for
Dlco measurement have improved in recent years with the use of rapid gas
analyzers.5
IRV
A normal value for Dlco indicates relatively normal gas exchange, which
IC
requires a normal pulmonary gas-exchanging surface, normal capillary blood
VC volume, and relatively homogeneous ventilation-perfusion relationships. A
low Dlco is indicative of impaired gas exchange. Among patients with obstruc-
tive disorders (Chapters 81 and 82), impaired gas exchange occurs most com-
EIV TLC monly in patients with emphysema as opposed to asthma. In restrictive disorders,
TV impaired gas exchange is seen most commonly in patients with interstitial
FRC disorders rather than patients with chest wall disorders. Patients with pulmo-
ERV nary vascular disorders typically have a low Dlco and may have restriction
RV or normal lung mechanics (Chapter 86). An isolated reduction in Dlco (i.e.,
in association with normal total lung capacity, vital capacity, and FEV1) can
FRC
indicate a pulmonary vascular disorder but is more commonly seen in associa-
tion with emphysema (Chapter 82), interstitial disease (Chapter 86), or a
RV
combination of the two.
An increased Dlco is relatively uncommon, most often seen in individuals
with asthma (Chapter 81) or obesity (Chapter 207). It can also be seen in
0 association with polycythemia (Chapter 157), left-to-right intracardiac shunt
FIGURE 79-2. A schematic diagram showing lung volume partitions as measured in (Chapter 61), and acute pulmonary hemorrhage (Chapter 85) during or after
lung function tests. EIV = end-inspiratory volume; ERV = expiratory reserve volume; FRC exercise, or in the supine position.
= functional residual capacity; IC = inspiratory capacity; IRV = inspiratory reserve volume;
RV = residual volume; TLC = total lung capacity; TV = tidal volume; VC = vital capacity. MAXIMAL RESPIRATORY PRESSURES
Maximal respiratory pressures help identify muscle weakness, which can cause
a restrictive disorder, a nonspecific pattern, or an isolated reduction in MVV
relative to FEV1. Maximal respiratory pressures do not distinguish muscle
is nitrogen. Exhaled air contains a lower concentration of oxygen, usually 14 weakness from poor test performance (Fig. 79-3).
to 16%, plus 3 to 5% carbon dioxide and water. For the nitrogen washout
technique, the test subject inhales 100% oxygen beginning at FRC. As the INTERPRETATION OF LUNG FUNCTION TESTS
subject breathes, exhaled gas is collected until the concentration of nitrogen The interpretation of pulmonary function tests uses the data obtained to infer
reaches a plateau. Knowing that the initial concentration of exhaled nitrogen a physiologic diagnosis and to categorize the nature and magnitude of the
is approximately 75% and measuring the final concentration and volume of impairments to lung function (Table 79-2). The four broad categories of physi-
gases collected, the initial volume of gas in the lungs at FRC can be calculated. ologic abnormalities include obstructive disorders, such as asthma and COPD
This method also underestimates lung volumes in patients with poorly com- (Chapters 81 and 82); restrictive disorders of the lung, such as pulmonary
municating air spaces. fibrosis (Chapter 86) or restriction due to factors outside the lung, such as
Lung volumes can also be measured from chest radiographs and computed chest wall limitation due to obesity, pleural disease, or musculoskeletal dis-
tomography scans. The correlation among the measurement techniques is orders; weak chest wall (Chapter 92), such as Guillain-Barré syndrome (Chapter
very good for people with reasonably normal lungs. In the presence of lung 392); and disorders resulting in impaired gas exchange with normal mechanical
disease, however, each of the methods has limitations. function, such as pulmonary embolism (Chapter 74). Some patients have
Absolute lung volumes as determined by body plethysmography or one mixed physiologic defects, such as a combined restrictive and obstructive
of the gas dilution methods can be used to refine the spirometric evalua- defect (see Fig. 79-3), or more than one cause of restriction (e.g., pulmonary
tion of both obstructive and restrictive disorders. In obstructive disorders, fibrosis plus obesity or heart failure).
air trapping or hyperinflation can be inferred from an increased residual Spirometry screening of the U.S. adult population shows evidence of airflow
volume, total lung capacity, or residual volume/total lung capacity (RV/ obstruction in about 13.5% of individuals and evidence of restriction in about
TLC) ratio. If the total lung capacity is greater than 125 to 130% of predicted, 6.5%. Of individuals with spirometric evidence of restriction, about 50% have
hyperinflation is present. A residual volume or RV/TLC ratio greater than true restriction when lung volumes are measured, whereas the other 50% have
the upper limit of normal suggests air trapping. However, in subjects with a nonspecific pattern of pulmonary function abnormality.
chest wall limitation or neuromuscular weakness, residual volume may be The first step in interpretation of a set of pulmonary function measurements
increased—not because of true airway trapping but because of limitation to is to inspect the numerical data, the spirogram, and the flow-volume curve to
expiratory chest wall movement, so the term air trapping should be used with assess the quality of the test. A poor-quality test result, whether it is due to
caution. poor performance by the patient or poor coaching by the technician, may have
A restrictive disorder can be inferred from a spirometry pattern showing a an irregular flow-volume curve (see Fig. 79-1L.) or poor reproducibility of
reduced FVC with a normal or increased FEV1/FVC ratio. To confirm the results from one effort to another. Once good quality is affirmed, the presence
presence of true restriction, lung volumes are required to demonstrate a TLC of an abnormal pattern (e.g., obstruction or restriction) can be determined.
less than the lower limit of normal. If TLC is normal, the pattern is called a If so, attention then turns to assessing gradations of severity, subtleties of
nonspecific pattern (see online supplement). the flow-volume curve, and other physiologic data (e.g., total lung capacity,
residual volume, MVV, and Dlco) that either support or supplement the
DIFFUSING CAPACITY initial impression.
The single-breath diffusing capacity for carbon monoxide (Dlco) is the most The normal flow-volume curve is roughly triangular (see Fig. 79-1A). A
common clinically used measure of the gas exchange capacity of the lungs. tracheal plateau, which is a normal variant (see Fig. 79-1J) usually seen in
The maneuver for measurement of Dlco requires breathing out to residual younger subjects, is caused by normal flow limitation in the trachea in the
volume and then quickly inhaling a mixture of gas with a known concentra- absence of peripheral airway obstruction.
tion of an inert gas (e.g., helium or neon) plus a small concentration of carbon Patients with obstructive disorders typically have a reduced FEV1/FVC ratio
monoxide. After inhaling to total lung capacity, the patient holds his or her and a flow-volume curve with a “scooped out” appearance (see Fig. 79-1B and
breath for 10 seconds, during which time the helium or other tracer gas mixes C). Atypical patients may have unusually shaped flow-volume curves or unusual
with other gases occupying the total lung capacity while the carbon monoxide patterns of obstruction (e.g., abnormal airway resistance despite a normally
is absorbed from the alveolar spaces because of the strong affinity of hemo- shaped flow-volume curve and normal FEV1/FVC ratio). If a patient has what
globin for carbon monoxide. After a 10-second breath-hold, the remaining appears to be obstruction, the next step is to determine the degree to which
522 CHAPTER 79 Respiratory Testing and Function

Examine FV curves +
consider quality
1
Normal or High Low

FEV1/FVC ratio
2
Normal Low Low

VC or FVC VC or FVC
8 3
Normal
Low Normal or High Normal Low
TLC TLC
Normal 9 4
spirometry
Restriction Nonspecific Obstruction Obstruction Mixed
14 High
Grade severity pattern Obstruction with air with pattern
trapping hyperinflation
11 10
Low Normal Airway High

DLCO BD response 5
12 Resistance Grade severity 6

Parenchymal
restriction Low/Normal
Normal
Normal Low or High Low
DLCO Chest wall MIP, MEP DLCO
15 limitation clinical 7
correlation
13
Normal Parenchymal Suggests Suggests
or vascular asthma emphysema
disorder
FIGURE 79-3. An algorithm for interpreting pulmonary function tests in which spirometry, lung volumes, and DLCO are measured. If only spirometry is available, interpretation is
more limited. The legend keys refer to numbered branch points in the algorithm. BD = bronchodilator; DLCO = diffusing capacity of the lung for carbon monoxide; FEV1 = forced expira-
tory volume in one second; FVC = forced vital capacity; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; Nl = normal; TLC = total lung capacity; VC = vital
capacity.
1. The algorithm begins at the top. Inspect the data and flow-volume (FV) curve to assess test quality and then consider the basic type of abnormality (e.g., obstruction vs.
restriction).
2. A reduced FEV1/FVC ratio suggests obstruction, and the obstruction algorithm on the right side should be followed. If the FEV1/FVC ratio is normal or high, the restriction side (left
side) of the algorithm should be followed.
3. If FEV1/FVC is low and the VC or FVC is normal or high, simple obstruction is present. If VC or FVC is low, TLC should be checked.
4. If TLC is normal, simple obstruction is present. If TLC is high, obstruction with hyperinflation is present. If TLC is low, a mixed obstructive/restrictive pattern is present. (Note that
the inert gas dilution and nitrogen washout methods commonly underestimate TLC in the presence of obstruction and can give a false impression of a mixed disorder.)
5. The response to a bronchodilator (BD) may be assessed to determine whether FEV1 or FVC meets criteria for a positive response (i.e., a ≥12% improvement and at least a 200 mL
absolute increase) and to determine the degree of positivity.
6. The severity of obstruction should be graded. Some algorithms grade severity based on post-bronchodilator values.
7. In current or former smokers with obstruction, a low DLCO suggests emphysema or other pulmonary parenchymal or vascular disorders. A normal DLCO may suggest asthma or
bronchitis.
8. If FEV1/FVC is normal or high, the restriction (left) side of the algorithm is followed. If VC or FVC is normal, spirometry is generally normal (occasional patients have an isolated
abnormality of FEV1 of uncertain significance). If VC or FVC is low, TLC should be checked.
9. If TLC is low, a restrictive disorder is present. If TLC is normal, the “nonspecific pattern” is present.
10. If the nonspecific pattern is identified, airway resistance (Raw) can be measured. An increased Raw suggests obstruction. A normal Raw suggests an alternative cause (See #13).
11. If true restriction is present, grade severity on the basis of the reduction in TLC percentage predicted.
12. If restriction is demonstrated, DLCO should be measured next. If abnormal, it indicates a pulmonary parenchymal restrictive process. If normal, it suggests an extraparenchymal or
nonpulmonary cause of restriction.
13. Restriction with a normal DLCO or a nonspecific pattern with normal Raw suggests an alternative cause (chest wall limitation, weakness, heart failure, poor performance). Consider
measurement of maximal respiratory pressures and review the study for test performance.
14. If spirometry is normal, lung volumes are rarely useful, but DLCO is sometimes helpful.
15. If DLCO is normal, pulmonary function is normal. An isolated reduction in DLCO is seen most often in patients with emphysema or pulmonary fibrosis or both. It less commonly
indicates a pulmonary vascular disorder, such as primary pulmonary hypertension, or an obliterative vasculopathy, as sometimes seen in Sjögren syndrome.
TABLE 79-2 COMMON CHANGES ASSOCIATED WITH PATTERNS OF LUNG FUNCTION ABNORMALITY
FORCED EXPIRATORY VOLUME FORCED VITAL FEV1/FVC RESIDUAL TOTAL LUNG MAXIMAL RESPIRATORY
IN 1 SECOND(FEV1) CAPACITY (FVC) RATIO VOLUME CAPACITY PRESSURES
Normal Normal* Normal Normal Normal Normal Normal
Obstructive ↓ Normal to ↓ ↓ ↑ to ↑↑ Normal to ↑↑ Normal
Restrictive ↓ ↓ to ↓↓ Normal or ↑ Normal or ↓ ↓ to ↓↓ Normal
Weak chest wall ↓ ↓ to ↓↓ Normal or ↑ ↑ Normal or ↓ ↓
*Normal or abnormal values are determined by comparing the measured values with those predicted from regression equations based on the patient’s sex, age, height, and race. The normal range for FEV1/FVC
also varies, mainly with age, ranging from 0.70 to 0.80 among 25-year-olds to 0.63 to 0.68 among 65-year-olds.

523
the obstruction can be reversed by the administration of a bronchodilator. testing, and chest imaging. For such patients, laboratory testing of physiologic
Hyperinflation or air trapping can be identified based on an increased total performance during exercise can be enlightening. Cardiopulmonary exercise
lung capacity or residual volume, and the adequacy of gas exchange can be testing, which is usually performed on a cycle ergometer or treadmill, includes
assessed by measuring Dlco and oximetry. For individuals with normal spi- monitoring of the heart rate, electrocardiography, and pulse oximetry as well
rometry and alveolar volume (from the Dlco), measurement of total lung as breath-by-breath measurement of tidal volume, breathing rate, oxygen con-
capacity can be avoided to save unnecessary expense. sumption, and carbon dioxide production. Optional measurements include
In obstructive diseases, the degree of impairment of pulmonary function arterial blood gases and noninvasive cardiac output. Outcomes include
can be classified on the basis of the FEV1. According to one commonly used maximal oxygen uptake (V̇ O2max), maximal workload, maximal heart rate,
scale, an FEV1 less than the lower limit of normal but greater than 70% is ventilation parameters during exercise, and measurements of gas exchange.
mild, 60 to 69% is moderate, 50 to 59% is moderately severe, 35 to 49% is Results are analyzed to determine if anaerobic metabolism occurs when the
severe, and less than 35% is very severe. study subject reaches maximal effort and to determine what limits the ability
Patients with restrictive disorders have reduced lung volumes and typically of a patient to exercise—a gas exchange abnormality, ventilatory limitation,
have a flow-volume curve with a “witch’s hat” shape—a tall peaked curve (see cardiac limitation, or deconditioning. Simple tests of exercise performance,
Fig. 79-1D and E). Restriction may be due to either reduced lung compliance such as the 6-minute walk test, can quantify and serially assess exercise
or mechanical changes to the chest wall and tissues surrounding the lungs performance.
(e.g., obesity, muscle weakness, chest wall deformity, pregnancy, pleural effu-
sion, or heart failure). For many restrictive diseases, the severity of the restric- BRONCHOALVEOLAR LAVAGE
tion can be graded with use of the total lung capacity as a percentage of the Bronchoalveolar lavage is useful for evaluation of opportunistic infections in
predicted value. Changes on serial testing help predict prognosis. immunocompromised hosts (Chapter 265),8 but its utility in the evaluation
In patients with restriction caused by interstitial disease, the total lung of interstitial lung disease is controversial. The procedure is generally safe,
capacity and the vital capacity or FVC are usually reduced by a similar propor- although provision must be made for the transient deterioration in gas exchange
tion. In some patients with restriction, the total lung capacity as a percentage after the procedure. Oxygen supplementation is usually necessary, and intuba-
of predicted and the vital capacity percentage of predicted are quite different tion and mechanical ventilation are sometimes needed.
(>10% difference). The usual cause is the presence of more than one restric- The differential cell count on a normal bronchoalveolar lavage specimen
tive process, such as a parenchymal restrictive disorder plus obesity, respiratory includes 85% macrophages or more, 10 to 15% lymphocytes, 3% neutrophils or
muscle weakness, atelectasis, or occult obstruction. Grading the severity of less, 1% eosinophils or less, 1% mast cells or less, and less than 5% squamous
such a “complex restrictive disorder”6 requires additional consideration. epithelial cells (which are an indicator of contamination from the upper airway).
Some patients have a mixed disorder with evidence of both obstruction Smokers may have higher cell counts and a higher percentage of neutrophils.
and restriction. Common causes include cystic fibrosis (Chapter 83), sarcoid- Increased lymphocyte counts are seen in sarcoidosis (Chapter 89), hypersensi-
osis (Chapter 89), and heart failure (Chapters 52 and 53) as well as cases in tivity pneumonitis (Chapter 88), nonspecific interstitial pneumonitis (Chapter
which the causes of the obstructive disorder and the restrictive disorder are 86), collagen vascular diseases (Chapter 86), radiation pneumonitis (Chapter
unrelated. 88), cryptogenic organizing pneumonia (Chapter 86), and lymphoproliferative
Disorders of the central airways can cause characteristic patterns of abnor- disorders. Increased neutrophil counts are seen in idiopathic pulmonary fibro-
mality. In a “fixed airway obstruction” such as tracheal stenosis (see Fig. 79-1H), sis (Chapter 86), collagen vascular diseases (Chapter 86), infectious pneu-
flow is typically reduced on both inspiration and expiration. In contrast, in a monia (Chapter 91), aspiration pneumonia (Chapter 91), acute respiratory
variable extrathoracic (upper) airway obstruction (see Fig. 79-1F), inspiration distress syndrome (Chapter 96), diffuse alveolar damage (Chapter 85), acute
is disproportionately reduced; however, expiration is often abnormal, merely interstitial pneumonia (Chapter 86), and asbestosis (Chapter 87). Increased
less so. Likewise, in variable intrathoracic obstruction (e.g., relapsing poly- eosinophils can be seen in asthma (Chapter 81), bronchitis (Chapter 90),
chondritis, tracheomalacia, or a dynamic intrathoracic tracheal tumor), the allergic bronchopulmonary aspergillosis (Chapter 319), eosinophilic granu-
expiratory flow-volume curve is reduced but in a pattern unlike that seen in lomatosis with polyangiitis (Chapter 254), Hodgkin lymphoma (Chapter
asthma or COPD (see Fig. 79-1G). These central airway obstructive patterns 177), and drug-induced lung disease (Chapter 88). If eosinophils are more
are often mistaken for COPD but may signify a locally treatable cause of than 25%, eosinophilic pneumonia is likely (Chapter 161). If lymphocytes
obstruction. are increased and the clinical differential diagnosis includes sarcoidosis or
In patients with heart disease, a decline in FEV1/FVC ratio is associated hypersensitivity pneumonitis, analysis of T-cell populations may be helpful;
with underfilling of the left heart and low cardiac output. By comparison, a the CD4:CD8 ratio is typically increased in sarcoidosis but reduced in hyper-
decline in FVC with preserved FEV1/FVC ratio is associated with left ven- sensitivity pneumonitis. If more than 20% of macrophages stain positive for
tricular hypertrophy and diastolic dysfunction.7 hemosiderin, diffuse alveolar hemorrhage is considered likely (Chapter 85),
particularly if lavage fluid is progressively bloody in successive aliquots of
lavage fluid.
PROVOCATIVE TESTING Cellular constituents of bronchoalveolar lavage are usually stained for cyto-
Assessing Airway Responsiveness logic analysis for malignant cells and viral inclusions. If Langerhans cell his-
Hyperresponsiveness of airways to the smooth muscle–contracting effect of tiocytosis (Chapter 86) is considered possible, 5% or more CD1a–positive
pharmacologic agents such as methacholine, as well as to cold air, dry air, and cells support the diagnosis. If chronic beryllium disease or beryllium sensitiza-
other physical stimuli, is characteristic of asthma (Chapter 81). It is also tion is possible, a lymphocyte proliferation test in response to exposure to
observed in COPD and other obstructive airway diseases. Bronchoprovoca- beryllium salts can be helpful (Chapter 87). Staining of solid material from
tion studies, in which graded doses of a stimulus are used to elicit airway the bronchoalveolar lavage with periodic acid–Schiff (PAS) stain for the pres-
constriction, are performed to measure airway responsiveness. A responsive ence of PAS-positive material is essential to the diagnosis of pulmonary alveolar
airway, that is, one in which a small stimulus leads to a fall in FEV1, may be proteinosis (Chapter 85). A diagnosis of lipoid pneumonia (Chapter 88),
used to confirm the diagnosis of asthma (Chapter 81). caused by the aspiration of oil, can be confirmed by an excess of lipid-laden
Exhaled nitric oxide is a marker of eosinophilic airway inflammation and macrophages from bronchoalveolar lavage. The presence of asbestos bodies
can be used to predict the likelihood that airway obstruction will improve or silica is not diagnostic of lung disease related to these substances (Chapter
with corticosteroid treatment. However, the utility of exhaled nitric oxide 87) but does indicate significant exposure.
levels for asthma management is controversial.
GENERAL REFERENCES
CARDIOPULMONARY EXERCISE TESTS
Some patients have dyspnea (Chapter 77) or exercise limitation that is not For the General References and other additional features, please visit Expert Consult
adequately explained by the clinical examination, standard pulmonary function at https://expertconsult.inkling.com.

523.e1
COMPLEX DISORDERS PULMONARY FUNCTION IN OBESITY

Many pulmonary function tests have more than one physiologic defect, such The epidemic of obesity is manifested in many organ systems, including the
as a combination of restriction plus obstruction, or more than one cause of respiratory system. Dyspnea, exercise limitation, and respiratory failure are
restriction (e.g., pulmonary fibrosis plus obesity or heart failure). These cases more common in obese persons than in the nonobese. Asthma is more common
do not fit neatly into standard interpretive patterns of typical obstruction or and more severe in obese patients. The effects of obesity on lung function are
restriction, yet they can be described, and their patterns suggest a differential usually relatively modest among ambulatory patients with a body mass index
diagnosis. (BMI) less than 40. The most commonly observed effect of obesity on lung
A mixed disorder is a combination of both restriction, as indicated by a function is a reduction in expiratory reserve volume (the amount of air exhaled
reduced TLC, plus obstruction, as indicated by a reduced FEV1/FVC ratio. between FRC and residual volume), which is substantially reduced even in
Although it is widely recognized, it only occurs in 1 to 2% of pulmonary persons who are overweight (BMI 25 to 30) or mildly obese (BMI 30 to 35).
function tests. A mixed disorder may be due to a combination of a restrictive Vital capacity is reduced in obesity, but the effect is modest, usually within
disorder plus an unrelated obstructive disorder, such as an interstitial disease the normal range, and highly variable. In large studies, vital capacity or FVC
plus COPD, but there are several disorders that typically produce a mixed is reduced on average by 0.5 to 0.8% for each unit increase in BMI above 25.
pattern including cystic fibrosis (Chapter 83), sarcoidosis (Chapter 89), Lang- Effects of obesity on total lung capacity and FEV1 are somewhat smaller. The
erhans cell histiocytosis (Chapter 160), and heart failure (Chapters 52 and FEV1/FVC ratio and Dlco actually increase slightly with increasing BMI.
53). In a mixed pattern, the degree of severity of restriction can be determined In exercise studies, the effects of obesity among ambulatory outpatients
from the TLC percent predicted. The overall impairment can be determined are likewise modest. Such patients have an increased work of breathing and
from the FEV1 percent predicted. The severity of the obstructive component decreased external work efficiency related to the work of moving their own
can be inferred from the FEV1 percent predicted divided by the TLC percent body mass, but maximal oxygen uptake is often normal.
predicted.
Reduced lung volumes are the sine qua non of the diagnosis of restriction.
However, about half of patients whose spirometry suggests restriction (reduced
vital capacity with normal FEV1/FVC ratio, also called preserved ratio impaired
spirometry or PRISM) have a normal total lung capacity, so they do not have
true restriction but rather what is called the nonspecific pattern. The nonspecific
pattern is very common, occurring in 9 to 10% of all complete pulmonary
function tests. It is approximately as frequent as true restriction. Patients with
the nonspecific pattern commonly have evidence of an obstructive disorder,
not restriction, as indicated either by increased airway resistance, a response
to a bronchodilator, or other clinical indicator of obstruction. It can be argued
that the clinical utility of the measurement of airway resistance is limited to
patients with the nonspecific pattern of whom about half have an increased
airway resistance. Some patients with a nonspecific pattern do not have evi-
dence of airway obstruction but are obese or have other chest wall limitations,
neuromuscular weakness, poor performance, heart failure, pleural effusion,
or a variety of other conditions.
In typical cases of restrictive lung disease, including most cases of interstitial
lung disease, lung volumes are reduced in proportion to the severity of the
interstitial disease. For example, TLC might be reduced to 60% of the predicted
value and FVC would be similarly reduced to about 60% of the predicted
value. In such a case, grading the severity of restriction is easy. One should
be cautious not to overlook the fact that the gas exchange abnormality may
be more or less severe, depending on the underlying pathology. In about one
third of cases of restriction, the reductions in FEV1 and FVC are dispropor-
tionate (>10% of predicted value) to the reduction in TLC. The discrepancy
may be large, for example TLC may be 70% predicted while FVC is only 25%
predicted. Interpreting physicians sometimes disagree whether to grade sever-
ity of restriction based on TLC percent predicted or FVC percent predicted.
In such a case, the impairment could be called either mild or very severe. In
a study of such cases, the term “complex restriction” was proposed. Whereas
cases of “typical restriction” were seen in association with interstitial lung
disease, and hence weighted toward older men, patients with “complex restric-
tion” were more often women, younger, underweight, had slightly less severe
reductions in Dlco, and more often had atelectasis, a mosaic pattern on com-
puted tomography, obesity, diaphragm dysfunction, or neuromuscular disease.
523.e2 CHAPTER 79 Respiratory Testing and Function

GENERAL REFERENCES 5. Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide
uptake in the lung. Eur Respir J. 2017;49:1-31.
1. Godfrey MS, Jankowich MD. The vital capacity is vital: epidemiology and clinical significance of the 6. Clay RD, Iyer VN, Reddy DR, et al. The “complex restrictive” pulmonary function pattern: clinical
restrictive spirometry pattern. Chest. 2016;149:238-251. and radiologic analysis of a common but previously undescribed restrictive pattern. Chest.
2. Thacher JD, Schultz ES, Hallberg J, et al. Tobacco smoke exposure in early life and adolescence in 2017;152:1258-1265.
relation to lung function. Eur Respir J. 2018;51:1-9. 7. Cuttica MJ, Colangelo LA, Shah SJ, et al. Loss of lung health from young adulthood and cardiac
3. Dempsey TM, Scanlon PD. Pulmonary function tests for the generalist: a brief review. Mayo Clin phenotypes in middle age. Am J Respir Crit Care Med. 2015;192:76-85.
Proc. 2018;93:763-771. 8. Sakata KK, Klassen CL, Bollin KB, et al. Microbiologic yield of bronchoalveolar lavage specimens
3b. Bhatt SP, Balte PP, Schwartz JE, et al. Discriminative accuracy of FEV1:FVC thresholds for COPD- from stem cell transplant recipients. Transpl Infect Dis. 2017;19:1-17.
related hospitalization and mortality. JAMA. 2019;321:2438-2447.
4. Cid-Juárez S, Thirión-Romero I, Torre-Bouscoulet L, et al. Inspiratory capacity and vital capacity of
healthy subjects 9-81 years of age at moderate-high altitude. Respir Care. 2019;64:153-160.

523.e3
REVIEW QUESTIONS
1. A 58-year-old man with exercise-related cough and a body mass index of 42 has a hemoglobin level of 14 g/dL, normal spirometry without a significant
bronchodilator response, and a diffusing capacity (Dlco) that is 144% of the reference value. The most appropriate next test is:
A . Bronchoalveolar lavage for hemosiderin-laden macrophages
B. Echocardiography to exclude intracardiac shunt
C. Quantitative assay for JAK2 mutation
D. Methacholine challenge
E. Measurement of hemoglobin P50
Answer: D Obesity and asthma are the most likely causes of an increased Dlco, and a search for rare causes of an increased Dlco usually is not indicated.
Bronchoalveolar lavage can be useful if clinical information suggests pulmonary hemorrhage. An echocardiogram may demonstrate a left to right shunt, which
is a rare cause of an increased Dlco. JAK2 mutations are associated with polycythemia vera, but the patient is not polycythemic.
2. A 61-year-old male former smoker (40 pack-years) complains of dyspnea and cough. Pulmonary function testing shows normal spirometry and lung
volumes; there is an isolated reduction in diffusing capacity (Dlco). The most useful next test is:
A . Echocardiography
B. Right-sided heart catheterization
C. High-resolution computed tomography of the chest
D. Maximal respiratory pressures
E. Bronchoalveolar lavage for hemosiderin-laden macrophages
Answer: C An isolated reduction in Dlco is most often associated with emphysema or fibrosis (or both), which are seen best with computed tomography.
An isolated reduction in Dlco is less often due to pulmonary vascular disorders such as pulmonary hypertension, so echocardiography and right-sided heart
catheterization may be valuable in some cases but would have a lower yield. Muscle weakness can reduce the Dlco, but it also reduces lung volumes. More
than 20% hemosiderin-laden macrophages on bronchoalveolar lavage is suggestive of diffuse alveolar hemorrhage, which is a rare cause of an increased Dlco.
3. A 53-year-old never-smoker with a saddle nose deformity has severe dyspnea and dry cough. His pulmonary function test results are as follows:
53 yo M
Ht = 177 cm
Wt = 89 kg
BMI = 28
Never-smoker
CONTROL %PRED
FVC 4.51 93
FEV1 1.52 40
FEV1/FVC 33.7 43
MVV 55 36
FEF50/FIF50 0.3 30
FEFmax 2.7 32
FIFmax 4.5 75
%PRED = percentage of predicted value
8
0
Flow Volume Curve
Predicted
–2 Control
Post dilator
–4
–6
–8

He reports episodes of ear pain and erythema, refractory to antibiotics but responsive to steroids. What is the next most appropriate test?
A . Methacholine challenge
B. Maximal respiratory pressures
C. Airway resistance
D. Imaging of the central airways (bronchoscopy or dynamic computed tomography)
E. Measurement of exhaled nitric oxide
Answer: D He has relapsing polychondritis. His main respiratory issue is dynamic central airway collapse due to chondromalacia of the tracheal and bronchial
cartilage. The flow-volume curve shows characteristic flattening, as opposed to the “scooped out” pattern of asthma and COPD. Inspiratory flows are normal.
He does not have a disorder of airway reactivity, so methacholine challenge adds little useful information and may not be safe with this degree of obstruction.
Maximal respiratory pressures are not likely to be abnormal. Airway resistance will be abnormal but will add nothing diagnostically. Exhaled nitric oxide is
abnormal in patients with eosinophilic airway inflammation and would not be expected to be abnormal in this case.
4. A patient with mild obstruction on spirometry has a maximal voluntary ventilation that is reduced out of proportion to the FEV1. Which of the following
is least likely to be helpful?
A . Maximal respiratory pressures
B. Inspiratory flow-volume curve
C. Cardiopulmonary exercise challenge
D. Airway resistance measurement
E. Careful scrutiny of test for repeatability of measures and technician comments on patient performance
Answer: C A disproportionate reduction in maximal voluntary ventilation may be due to inspiratory obstruction, muscle weakness, or poor performance.
Cardiopulmonary exercise testing is likely to be abnormal regardless of the cause of the abnormality. The other four options would yield more specific diagnostic
information.
5. A 34-year-old man is being evaluated for dyspnea and lack of energy. Results are as follows: TLC, 62% predicted; FVC, 40%; FEV1, 36%; FEV1/FVC,
0.90%; Dlco, 60%. The expiratory flow-volume curve is as shown:
12 0
Flow Volume Curve
Maximal Inspiratory Flow, liters/sec

FET
Predicted
10 Control 3.9 2
8 4
6 6
4 8
2 10
0 12
0 1 2 3 4 5 6 7 8
Expired Volume, liters
What test is likely to be most helpful?

A . Maximal respiratory pressures
B. Airway resistance
C. Methacholine challenge
D. Cardiopulmonary exercise test
E. Arterial blood gases
Answer: A The convex shape of the flow-volume curve in an adult suggests muscle weakness or poor performance. In a patient with restriction, the dispro-
portionate reduction in FVC compared with TLC may be due to muscle weakness. This patient has a myopathy. Alternative considerations include chest wall
limitation, poor performance, and occult airflow obstruction. The most helpful measurements on this patient will be maximal respiratory pressures, which will
likely result in referral to a neurologist. Airway resistance is unlikely to be abnormal with this flow-volume curve. There is little to suggest asthma, and an
exercise study is likely to be abnormal but may not reveal the cause of the abnormality. Arterial blood gases are usually normal in neuromuscular disorders
until the FEV1 and FVC are severely reduced, after which hypercapnia develops as an indicator of respiratory failure.

523.e5
6. A 40-year-old woman is referred for second opinion about her “asthma.” She has never smoked and has been symptomatic since a hospitalization after a
motor vehicle accident 10 years ago. She has not responded to bronchodilators and inhaled steroids. This is her first spirometry test.
40 yo F
Ht = 178 cm
Wt = 79 kg
BMI = 25
CONTROL %PRED
TLC 5.73 83
RV 2.32 124
RV/TLC 0.41 148
FVC 3.40 68
FEV1 1.51 38
FEV1/FVC 44.5 56
MVV 11 7
FEF50/FIF50 1.1 110
DLCO (hb adj) 18.58 61
SpO2 98
%PRED = percentage of predicted value.
6
Expiratory Flow, liters/sec
Expired
0 Volume (L)
1 2 3 4 Inspired
Inspiratory Flow, liters/sec
What test is most likely to be helpful?

A . Computed tomography of the chest
B. Oral exhaled nitric oxide
C. Methacholine challenge
D. Laryngoscopic examination of the upper airways
E. Sputum examination for Charcot Leyden crystals and Curschmann spirals
Answer: D She has tracheal stenosis, which resulted from prolonged intubation or tracheostomy after her motor vehicle accident. CT of the chest does not
always identify tracheal stenosis. Oral exhaled NO, methacholine challenge, and examination of the sputum for Charcot Leyden crystals and Curschmann
spirals all are manifestations of asthma, but her flow-volume curve has the characteristic appearance of tracheal stenosis, not asthma. The tracheal stenosis is
obvious on examination of the flow-volume curve and reinforces the need to perform spirometry for evaluation of patients thought to have common obstruc-
tive disorders such as asthma and COPD.
Suggested Interpretation: Abnormal. Severe fixed airway obstruction is indicated by the reduced FEV1 and MVV and shape of the inspiratory and expira-
tory flow-volume curves. There is no immediate response to bronchodilator. Dlco is mildly reduced, consistent with a pulmonary parenchymal or vascular
process. Lung volumes and oxygen saturations are normal.

7. An 80-year-old man who underwent right pneumonectomy 16 years ago for lung cancer has severe aortic stenosis and severe coronary disease. He has
pulmonary function testing before aortic valvuloplasty.
12
Flow Volume Curve

10 PRED mayo
Control
Post dilator
8
0
0 1 2 3 4 5 6 7
80 yo M
Ht = 185 cm
Wt = 66 kg
BMI = 19
CONTROL %PRED
TLC 5.37 73
RV 3.53 142
RV/TLC 0.66 194
FVC 1.86 38
FEV1 1.25 35
FEV1/FVC 67.5 91
MVV 33 27
Max Insp Press 25 25
Max Exp Press 29 16
DLCO (hb adj) 9.5 38
SpO2 100 99
How would you interpret his results?

A. Mild restriction
B. Severe restriction
C. Mild-to-severe restriction
D. Severe mixed obstruction/restriction
E. Severe complex restrictive disorder
Answer: E This illustrates the dilemma posed by conventional thinking about grading restriction. Should one call this mild based on TLC or severe based on
FVC or split the difference and call it mild-to-severe? When the reductions in TLC and FVC are discordant by more than 10%, there is usually a second process
contributing to the restriction. In this case, the processes are a combination of pneumonectomy, heart failure, and weakness.
Suggested Interpretation: Abnormal. Complex restriction. A restrictive process is indicated by the mild reduction in TLC. The disproportionately severe
reductions in vital capacity and FEV1, relative to TLC, suggests an additional process, which might include chest wall limitation, muscle weakness, poor per-
formance, heart failure, or occult obstruction. Dlco (adjusted for hemoglobin) is severely reduced, consistent with a pulmonary parenchymal or vascular
process or anemia. Oximetry is normal at rest and during exercise.

523.e7
8. A 52-year-old woman with primary biliary cirrhosis, type 2 diabetes, and moderate persistent asthma was evaluated for increasing dyspnea.
52 yo F
Ht = 168 cm
Wt = 103 kg
BMI = 37
CONTROL %PRED POST DILATOR %CHANGE
TLC 5.22 97
RV 2.62 141
RV/TLC .50 69
FVC 2.45 69 3.10 26
FEV1 1.98 69 2.37 20
FEV1/FVC 80.6 100 76.7
MVV 74 70
Raw 18.6 400
DLCO (hb adj) 25 107
SPO2 97 96
12
Flow Volume Curve
PRED
10 Control
Post dilator
0
0 1 2 3 4 5 6 7
How would you interpret her results?

A. Moderate restriction
B. Moderate obstruction
C. Poor test performance
D. Nonspecific abnormality
E. Complex restrictive disorder
Answer: D This pattern fits neither obstruction, because of the normal FEV1/FVC ratio, nor restriction, because of the normal TLC. The patient’s successive
efforts were highly repeatable, within less than 150 mL, arguing against poor performance. The findings do not fit the description of complex restriction, because
although the FVC % predicted is less than TLC % predicted, the TLC is not abnormal. This nonspecific pattern was described in 2009 and further character-
ized in 2011. It was previously thought that this pattern represented a variant of obstruction, and it is frequently associated with obstructive disorders, such as
this patient’s asthma. However, 30 to 40% of cases have no evidence of obstruction but rather some form of chest wall limitation, such as obesity, muscle
weakness, or chest wall deformity. For this patient, airway resistance was measured to evaluate the nonspecific pattern and proved to be very high. In addition,
the shape of the flow-volume curve and the response to bronchodilator suggest an obstructive process.
Suggested Interpretation: Abnormal. FVC and FEV1 are moderately reduced in a nonspecific pattern with a normal TLC and FEV1/FVC ratio. The shape
of the flow-volume curve, the increased airway resistance and the improved flows after bronchodilator all suggest a partly reversible obstructive process. Dlco
and oximetry at rest and during exercise are all normal.

9. A 62-year-old man is being evaluated for hematuria, coronary artery disease, peripheral arterial disease with an ischemic foot ulcer, and type 2 diabetes.
He has smoked a pack of cigarettes per day for 40 years and quit 7 years ago. He complains of dyspnea on exertion.
62 yo M
Ht = 189 cm
Wt = 125 kg
BMI = 35
FVC 5.08 92 5.53 9
FEV1 4.12 98 4.11 0
FEV1/FVC 81.2 107 74.3
MVV 127 84
DLCO 29.8 100
SPO2 94 93
12
Flow Volume Curve
10 PRED
Control
Post dilator
8
0
0 1 2 3 4 5 6 7
What is the most appropriate next test?

A . CT of the chest
B. Overnight oximetry
C. Cardiopulmonary exercise test
D. Arterial blood gas
Answer: B Chest CT is not indicated by findings from pulmonary function testing. Nevertheless, it was done for lung cancer screening purposes. Like many
U.S. Midwesterners, this patient has several indeterminate lung nodules that require follow-up. Cardiopulmonary exercise testing, if performed, might show
evidence of deconditioning and also might identify evidence of myocardial ischemia. It was not performed because of the patient’s ischemic foot. A nuclear
stress test was performed instead. It showed no evidence of stress-induced ischemia or infarction. Left ventricular size and function appeared to be normal.
The patient had no evidence of hypoxemia, and hypercapnia would be unlikely with normal spirometry, so arterial blood gases were not obtained. An overnight
oximetry showed frequent nocturnal desaturations with a pattern suggesting REM accentuation. The patient has severe obstructive sleep apnea as evidenced
by the sawtooth abnormality, which indicates a two-fold increase in the likelihood of obstructive sleep apnea compared with normal subjects.
Suggested Interpretation: Numerical results of spirometry, DLCO and oximetry are normal, however, the sawtooth configuration of the flow-volume curve
indicates redundant tissue in the upper airway. This correlates with snoring and may be predictive of obstructive sleep apnea.
Bourne MH, Jr., Scanlon PD, Schroeder DR, et al. The sawtooth sign is predictive of obstructive sleep apnea. Sleep Breath. 2017;21:469-474.

523.e9
10. A 58-year-old woman is a current smoker with a 40 pack-year smoking history. She is severely dyspneic and is oxygen dependent.
58 yo F
Ht = 162 cm
Wt = 60 kg
BMI = 23
TLC 5.19 103
RV 1.39 75
RV/TLC .27 73
FVC 3.40 107 3.33 −2
FEV1 2.56 100 2.62 2
FEV1/FVC 75.3 93 78.7
MVV 96 99
DLCO 7.0 32
SPO2 91 (rest) 73 (exercise)
12
Flow Volume Curve
10 Predicted
Control
Post dilator
8
0
0 1 2 3 4 5 6 7
What is the most likely cause of this abnormality?

A . Emphysema
B. Pulmonary fibrosis
C. Both A and B
D. Primary pulmonary hypertension
Answer: A This is an isolated reduction in Dlco, which is often found in patients with emphysema or pulmonary fibrosis or both. Combined pulmonary
fibrosis and emphysema is a recognized entity, mostly in current and former smokers. The curious aspect of this dual disease entity is that the increased lung
recoil caused by the fibrosis can counterbalance the loss of recoil from emphysema. In some cases, the two are matched, thereby preserving airway patency
and resulting in normal airflows and lung volumes as in this case. In other cases, however, either the restrictive or the obstructive physiology may predominate.
Both processes impair gas exchange, however, often resulting in a very low Dlco as in this case. This patient had severe diffuse fibrosis with honeycombing
plus emphysematous changes, particularly in the upper lungs.
Suggested Interpretation: Abnormal. TLC, FEV1, FVC, FEV1/FVC and MVV are within accepted ranges of normal. Dlco is severely reduced, consistent
with emphysema or other pulmonary vascular or parenchymal process. Oxygen saturation is slightly reduced at rest and decreases markedly during exercise.
Tzilas V, Bouros D. Combined pulmonary fibrosis and emphysema, a clinical review. COPD Research and Practice. 2016;2:2. DOI: 10.1186/s40749-016
-0018-1.

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518 CHAPTER 79 Respiratory Testing and Function

of bronchoalveolar lavage fluid, obtained by bronchoscopy, can also provide

Maximal Expiratory Flow, liters/sec

Maximal Expiratory Flow, liters/sec

Moderate Restriction Severe Restriction Variable Extrathoracic Obstruction

Maximal Expiratory Flow, liters/sec

Control Control Control

Variable Intrathoracic Obstruction Fixed Obstruction Weakness

Maximal Expiratory Flow, liters/sec

8 Control Control Maximal Expiratory Flow, liters/sec Control

Normal with Prominent Sawtooth Pattern Poor Performance

Maximal Expiratory Flow, liters/sec

Control PRED mayo FET

Normal or High Low

Normal Low Low

Low Normal Airway High

12 Resistance Grade severity 6

COMPLEX DISORDERS PULMONARY FUNCTION IN OBESITY

Maximal Inspiratory Flow, liters/sec

What test is likely to be most helpful?

What test is most likely to be helpful?

Maximal Expiratory Flow, liters/sec

How would you interpret his results?

How would you interpret her results?

What is the most appropriate next test?

What is the most likely cause of this abnormality?

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