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FIGURE 14-2. Flow- volume curves seen with obstructive and restrictive pulmonary diseases. This gure illustrates
the ow- volume curves observed for normal adults: obstructive, restrictive, and mixed disease. Flow- volume curve
number 1 represents baseline spirometry. Flow- volume curve number 2, if present, is a repeat of the spirometry after
a bronchodilator is administered. (Refer to bronchodilator studies under Bronchodilator Responsiveness Test.) The
curve with the vertical lines represents the predicted normal values. In these examples, there is no improvement in
the ow- volume curves after bronchodilator administration. The normal ow- volume curve shows that the curve is
larger than expected based on predicted values and is, therefore, normal. Concavity of the expiratory portion of the
curve, consistent with limitation in ow compared with the predicted, is illustrated in the airow limitation owvolume curve. The restriction ow- volume curve shows a FVC that is smaller than expected. The predicted volume
is approximately 3 L; however, the patient’s FVC is 2 L. In restriction, although the forced expiratory ows are often
decreased, there is no concavity such as seen in the airow limitation curve. It is important to note that spirometry
does not diagnose restriction. The ow- volume loop demonstrates ndings such as this consistent with restriction;
however, lung volumes are needed to dene restriction. Concavity in the expiratory phase and a decreased FVC
volume is consistent with a combination of an airow limitation and restriction ow- volume curve.
CHAPTER 14 • PulmonARy FunCTion And RElATEdTEsTs 307
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maintaining an upright posture, until all the air is exhaled. e
patient is then instructed to inspire with maximal eort until
completely full. is maneuver can be repeated up to eight times
in adults if needed to meet testing standards.
Like most medical tests, spirometry has seen changes over
the years in equipment, computer support, and recommendations for standardization. In an eort to maximize the usefulness
of spirometry results, the American oracic Society (ATS),
in conjunction with the European Respiratory Society (ERS),
developed standardizations of spirometry testing.
3,4
These
recommendations are intended to decrease the variability of spirometry testing by improving the performance of the test. e
recommendations cover equipment, quality control, the training and education of people conducting the test, and the training of patients performing the test. e recommendations also
provide criteria for acceptability and usability of the patient’s
spirometry eorts and guidelines on interpreting the spirometry
test results. For acceptability and usability of both the FEV1 and
FVC results, three criteria must be met. e rst criterion is the
back- extrapolated volume (BEV), which must be ≤5% of the
FVC or 0.100 L, whichever is greater. BEV is the volume of gas
exhaled before the start of forced expiration. e BEV would be
too high if a patient leaked out air before maximal exhalation.
Spirometers show the BEV calculation. e second criterion is
the measurement must have no evidence of a faulty zero- ow
setting, or airow through the mouthpiece sensor before the
start of the test. Newer spirometers use technology to detect this
error and alert the user. e last criterion is there must be no
glottic closure in the rst second of expiration. Glottic closure
appears like a at line on the volume- time graph and shows a
stop in airow. Because the results of spirometry depend on the
patient’s eort, at least three acceptable eorts are obtained with
a goal of having the two highest measurements of FVC and FEV1
vary ≤0.150L if the patient’s age is >6 years and FVC and FEV1
vary ≤0.100L or 10% of the highest value, whichever is greater
for patients 6 years of age and younger.
4
Bronchodilator Responsiveness Test
One of many tests that may be useful in the diagnostic workup of
asthma is spirometry with bronchodilator responsiveness to assess
airow variability. Before the testing day, the patient is asked
to hold short- acting β2- agonists (SABA) for at least 4 hours;
twice daily long- acting β2- agonists (LABA) for at least 12 hours
and once- daily LABA for at least 24 hours; and ultra-LABA for
36hours and long- acting muscarinic antagonists for 48 hours.4 Spirometry is performed at baseline and then again 15 to 30 minutes aer the administration of an inhaled SABA. A positive
bronchodilator response is dened as an improvement of the
postbronchodilator FEV1 and FVC by at least 12% and 200 mL
from the prebronchodilator measurement.7 e Global Initiative
for Asthma denes airway reversibility in adults as an increase
in FEV1 of at least 12% and 200 mL from the prebronchodilator
measurement, with more condence of a positive test with an
increase in FEV1 of at least 15% and 400 mL from baseline. For
children, an increase of at least 12% of predicted for the FEV1
is considered positive.6 Minicase 1 illustrates how spirometry is
used to conrm COPD and how the bronchodilator reversibility
study is useful for diagnosing asthma.
Peak Expiratory Flow
e peak expiratory ow (PEF) is measured with a simple, inexpensive hand- held peak ow meter that can be used at a patient’s
home, in the clinician’s oce, or in the emergency department.
Because PEF measures airow through the upper airway over a
shorter time and readings can vary depending on the patient’s
eorts and meter type, it is not the preferred test to detect airow limitation.
When spirometry is not available, PEF can be used to help
diagnose asthma by assessing diurnal variability.
ability is indicative of asthma when the diurnal variability is
>10% aer 1 to 2 weeks in adults and >13% for children.6 One
can calculate diurnal variability by dividing [day’s highest PEF
minus day’s lowest PEF] by the mean of these two values and
then averaging these daily variability results over 1 week.9 Twicedaily PEF is measured in the morning before using inhalers and
in the aernoon or evening. Variability decreases aer about
3months of use an inhaled corticosteroid.
Peak ow meters are designed for both pediatric and adult
patients with PEFR between 60 and 400 L/min for children and
between 60 and 850 L/min for adults. PEFR is measured by having a patient perform the following steps:
1. Stand up.
2. Move the indicator on the peak ow meter to the end near-
est the mouthpiece.
3.
Hold the meter and avoid blocking the movement of the indi-
cator and the holes on the end of the meter.
4.
Take a deep breath in and then seal the mouth around the
mouthpiece.
5.
Blow out into the meter as hard and as fast as possible without
coughing into the meter (like blowing out candles on a cake).
6. Examine the indicator on the meter to identify the number
corresponding to the peak ow measurement.
7.
Repeat the test two more times (remembering to move the
indicator to the base of the meter each time).
8.
Record the highest value of the three measurements in a
diary (readings in the morning and aernoon are ideal).
To establish a patient’s personal best peak ow rate, measure
the peak ow rate over a 2- week period when asthma symptoms and treatment are stable. e highest value over the 2- week
period is the personal best. Using the individual patient’s personal best peak ow instead of predicted peak ow values is considered best practice. Asthma patients typically have lower peak
ow readings than the healthy population, and using predicted
values may result in overtreatment.
Using PEF for long- term monitoring is helpful for patients
who have sudden asthma exacerbations or severe asthma.
Improved asthma outcomes have been seen in asthma action
plans, including personal best PEF. PEF is also helpful for
6,8
Diurnal vari
-
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MINICASE 2
Six-Minute Walk Test
Charles O. is a 65- year- old man diagnosed with World Health
Organization group 1 pulmonary arterial hypertension after
completing a right-
heart catheterization. He reports a persistent
room in his home with use of oxygen via nasal cannula at 6 L/min
with exertion only. His medications were changed 6 months ago
because he was experiencing side effects.
and progressive dyspnea on exertion with walking from room to
Tes t 1. Baseline
HEART RATE
SpO2 (%)
(beats/min)
Baseline on room air 89 69 100/69 Room air
Baseline on supplemental oxygen
Minute 1 90 96 Room air
Minute 2 86 104 Room air
Minute 3 83
85
109
112
Minute 4 89 114 6 L/min O
Minute 5 89 115 6 L/min O
Minute 6 90 115 104/69 6 L/min O
Recovery 2nd minute 89 65 106/75 Room air
BLOOD PRESSURE
(mm Hg)
SUPPLEMENTAL
OXYGEN (L/min)
2 L/min O
4 L/min O
NC
2
NC
2
NC
2
NC
2
NC
2
Distance walked 274.3 m
Number of rests 0
Borg scale self- rate Pretest Posttest
Dyspnea 2 5
Fatigue 2 5
NC = nasal cannula.
Tes t 2. 6 Months Later
HEART RATE
SATURATION (%)
(beats/min)
Baseline on room air 90 81 109/78 Room air
Baseline on supplemental oxygen
Minute 1 91 88 Room air
Minute 2 88 103 Room air
Minute 3 86 113 3 L/min O
Minute 4 88 115 4 L/min O
Minute 5 90 116 6 L/min O
BLOOD PRESSURE
(mm Hg)
SUPPLEMENTAL
OXYGEN (L/min)
NC
2
NC
2
NC
2
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MINICASE 2 (cont’d)
Tes t 2. 6 Months Later
HEART RATE
SATURATION (%)
Minute 6 90 118 108/81 6 L/min O
Recovery 2nd minute 90 70 112/79 Room air
Distance walked 320 m
Number of rests 0
Borg scale self-
Dyspnea 2 3
Fatigue 2 4
NC = nasal cannula.
QUESTION: Do the results from this patient’s 6- month 6MWT show
an improvement in distance walked after his medications were
changed?
DISCUSSION: According to the first 6MWT, the patient walked
274.3 meters. He required 6 L/min of oxygen with exercise. The
patient’s distance walked was 48% of the LLN. The patient became
tachycardic with exertion, which improved after a 2- minute recovery
rate Pretest Posttest
(beats/min)
period. The results of the second 6MWT show the patient walked
for 320m with no rests. The patient required 6 L/min supplemental
oxygen with exertion. Comparing his 6MWT after starting the new
medication regimen, the patient’s 6- minute walk distance improved
by 45.7m and his oxygen requirement remained unchanged.
A distance greater than a 30important.20 The patient has improved with the medication change.
BLOOD PRESSURE
(mm Hg)
m walk is considered clinically
SUPPLEMENTAL
OXYGEN (L/min)
NC
2
identifying environmental and occupational asthma triggers along with dierentiating between asthma and anxiety
symptoms.
6
Body Plethysmography
Body plethysmography is a method used to obtain lung volume
measures. Lung volume tests indicate the amount of gas contained
in the lungs at the various stages of ination. e lung volumes
and capacities may be obtained by several methods, including
body plethysmography, gas dilution, and imaging techniques.10
Dierent methods can have small but signicant eects on the
values reported. Gas dilution methods only measure ventilated
areas, whereas body plethysmography measures both ventilated
and nonventilated areas. erefore, body plethysmography values
may be larger in patients with nonventilated or poorly ventilated
lung areas. Computed tomography (CT) and magnetic resonance
imaging can estimate lung volumes with additional detail of the
lung tissue. Because body plethysmography is the most used
method, this technique is discussed in more detail.
In body plethysmography, a patient sits in an airtight box
and is told to inhale and exhale to functional residual capacity
(FRC), or the volume of gas remaining at the end of a normal
breath. Inside, a mouthpiece contains a pressure transducer.
is is done to measure the change in pressure within the box
during respiration. It senses the intrathoracic pressure generated when the patient rapidly and forcefully pus against the
closed mouthpiece. ese data are then placed into the equation for Boyle’slaw:
P1 × V1 = P2 × V
2
where P1 is pressure inside the box in which the patient is
seated (atmospheric pressure), V1 is volume of the box, P2 is
intrathoracic pressure generated by the patient, and V2 is the
calculated volume of the box at the end of chest expansion.
e dierence between this V2 and the initial volume of the
box is the change in the volume of the box which is the same
as the change in the volume in the chest. Because temperature
(T1 and T2) is constant throughout testing, it is not included in
the calculations.
Using this change in volume in Boyle’s law again, this test
provides a measure of the FRC. Once the FRC is determined,
the other lung volumes and capacities can be calculated based
on this FRC and volumes obtained in static spirometry. Aer
these data are generated, the patient’s plethysmography results
are usually compared with references from a presumed normal
population. is comparison necessitates the generation of predicted values for that patient if he or she were completely normal
and healthy. rough complex mathematical formulas, sitting
310 BASIC SKILLS IN INTERPRETING LABORATORY DATA
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and standing height, age, sex, race, barometric pressure, and
altitude are factored in to give predicted values for the pulmonary functions being assessed. e patient’s results are compared
with the percentage of predicted values based on the results of
these calculations.
Lung Volumes and Lung Capacities
Lung volumes include tidal volume (TV), inspiratory reserve
volume (IRV), expiratory reserve volume (ERV), and residual
volume (RV). ese four volumes in various combinations make
up lung capacities, which include inspiratory capacity, FRC, SVC,
and total lung capacity (TLC).
Tidal Volume, Functional Residual Capacity, Expiratory
Reserve Volume, and Residual Volume
e tidal volume is the amount of air inhaled and exhaled at
rest in a normal breath. It is usually a small proportion of the
lung volume and is infrequently used as a measure of respiratory disease. e IRV is the volume measured from the “top” of
the TV (ie, initial point of normal exhalation) to the maximal
inspiration. During exhalation, the ERV is the volume from the
“bottom” of the TV (ie, initial point of normal inhalation) to
maximal expiration. e RV is the volume of air le in the lungs
at the end of forced expiration to the bottom of ERV. Without the
RV, the lungs would collapse like deated balloons. In diseases
characterized by airow limitation that trap air in the lungs (eg,
COPD), the RV increases and the patient is less able to mobilize
trapped air out of the lung. ese four lung volumes are depicted
in Figure14-3.
Inspiratory Capacity, Functional Residual Capacity,
Slow Vital Capacity, and Total Lung Capacity
e inspiratory capacity is the volume measured from the point of
the TV at which inhalation normally begins to maximal inspiration, and it is a summation of TV and IRV. e functional residual
capacity is the sum of the ERV and RV, and it is the volume of
gas remaining in the lungs at the end of the TV. It also may be
dened as a balance point between chest wall forces that increase
volume and lung parenchymal forces that decrease volume. An
increased FRC represents hyperination of the lungs and usually
indicates airow limitation. e FRC may be decreased in diseases
that aect many alveoli (eg, pneumonia) or by restrictive changes,
especially those due to brotic pulmonary tissue changes. e
SVC is the volume of air that is exhaled as much as possible aer
inhaling as much as possible. It is a summation of the IRV, TV,
and ERV and is described in more detail in the Spirometry Measurements section. e total lung capacity is the summation of all
four lung volumes (IRV + TV + ERV + RV). It is the total amount
of gas contained in the lungs at maximal inhalation. Restrictive
lung disease is dened as a TLC below the 5th percentile of normal predicted value with a normal FEV1/VC ratio.
7
Diffusion Capacity Tests
Tests of gas exchange measure the ability of gases to cross (diffuse) the alveolar- capillary membrane and are useful in assessing
interstitial lung disease.11 Typically, these tests measure the perminute transfer of a gas, usually carbon monoxide (CO), from
the alveoli to the blood. CO is used because it is a gas that is not
normally present in the lung, has a high anity for Hgb in red
blood cells, and is easily delivered and measured. e diusion
capacity may be lessened aer losses in the surface area of the
alveoli or thickening of the alveolar- capillary membrane. Membrane thickening may be due to inltration of inammatory
cells or brotic changes. ese test results can be confounded
by a loss of diusion capacity due to poor ventilation, which
may be related to closed or partially closed airways (as with airow limitation) or to a ventilation- perfusion mismatch (as with
pulmonary emboli or pulmonary hypertension). e diusion
capacity of the lungs to CO can be measured by either a singlebreath test or steady- state test.
Inspiratory Capacity (IC)
Vital Capacity (VC)
Total Lung Capacity (TLC)
Tidal Volume (TV)
Expiratory Reserve Volume (ERV)
Functional Residual
Capacity (FRC)
Residual Volume (RV)
Inspiratory
Reserve Volume
(IRV)
FIGURE 14-3. Lung volumes and capacities. Representation of various lung compartments based on a typical
6
spirogram. Refer to Pellegrino et al
for more information.
CHAPTER 14 • PulmonARy FunCTion And RElATEdTEsTs 311
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In the single- breath test, the patient deeply inhales— to vital
capacity— a mixture of 0.3% CO, a tracer gas such as 10% helium
or 0.3% methane, and balanced air. Aer holding his or her
breath for 10 seconds, the patient exhales fully, and the concentrations of CO and helium are measured during the end of
expiration (ie, alveolar ow). ese concentrations are compared
with the inspired concentrations to determine the amount diffusing across the alveolar membrane. e mean value for CO is
disease (asbestosis and silicosis), or be induced by drugs (eg,
nitrofurantoin, amiodarone, and bleomycin).
alters Hgb, decreases the red blood cell Hgb concentration, or
changes diusion across the red blood cell membrane may alter
the DLCO. e DLCO also reects the pulmonary capillary
blood volume. An increase in this volume (pulmonary edema
or asthma) may increase the DLCO. Minicase 3 describes how
PFTs are used to diagnose restrictive airway disease.
about 25 to 30 mL/min/mm Hg.
A normal DLCO using a cuto of the percent predicted has
not been standardized but 70% to 75% if oen utilized. A normal DLCO is also considered when greater than the LLN for the
patient. Diusion capacity is decreased in diseases that cause
alveolar brotic changes. Changes may be idiopathic, such as
those seen with sarcoidosis or environmental or occupational
Specialized Tests
Bronchial Challenge Tests
Bronchial challenge tests (BCTs) are used to (1) aid in the diagnosis of asthma when the more common tests (symptom history, spirometry with reversibility) cannot conrm or reject the
MINICASE 3
Using Pulmonary Function Tests to Evaluate a Patient with
Interstitial Lung Disease
Jacob K. is a 59- year- old man who presents to the medicine clinic
with reports of progressive dyspnea on exertion and minimal
dry cough for the past 3 months. He has a history of rheumatoid
arthritis and was started on methotrexate 4 months ago. CT of the
chest shows diffuse ground glass opacities consistent with active
inflammation and some minimal fibrosis at the bases. He had a PFT
performed over a year ago that was completely normal. A repeat
PFT is ordered and includes spirometry, lung volumes, and diffusion
capacity. His PFT reveals the following results and the flow- volume
curve in Figure14-2 labeled “Restriction.”
QUESTION: How are these PFTs useful in the diagnosis, evaluation,
and management of this patient?
DISCUSSION: Looking at his PFT in the following table, the FVC is
56% of predicted (reduced), the FEV1 is 60% of predicted (reduced),
and the FEV1/FVC ratio is 0.85 (normal). This is consistent with a
restrictive pattern. A TLC is 54% of predicted (reduced), verifying
a restrictive pulmonary defect, and the DLCO is 50% of predicted
(normal range is ≥70–75% of predicted). These findings are helpful
in the diagnosis of interstitial lung disease in the setting of abnormal
results on CT scan and change from previous normal spirometry.
The severity of restriction can also be determined by the amount
of decrease in TLC.
6
12,13
Anything that
PREBRONCHODILATOR POSTBRONCHODILATOR
PFT LLN MEASURED % PREDICTED MEASURED % CHANGE
FVC (L) 4.09 3.03 56 3.11 +2
FEV
(L) 3.10 2.48 60 2.65 +6
1
FEV
/FVC 0.82 0.85 +3
1
SVC (L) 4.09 3.06 57
TLC (L) 6.54 4.36 54
RV (L) 1.71 1.30 51
DLCO (mL/min/mm Hg) 22.06 15.99 50
He is diagnosed with methotrexate- induced lung disease. The
methotrexate is discontinued, and he is treated with prednisone.
After 3 months of therapy, a repeat PFT is performed. The FVC is
75% of predicted, the FEV1 is 72% of predicted, and the FEV1/FVC
ratio is 0.80. The TLC has increased to 65%, and the DLCO has
increased to 60% of predicted. The repeat PFT shows that he is
improved. He reports improvement in his symptoms. The follow- up
PFT is used to help evaluate the response to discontinuing the
offending medication and establish a new pulmonary function
status.
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diagnosis, (2) evaluate the eects of drug therapy on airway
hyperreactivity, and (3) evaluate potential drug eectiveness.
ABCT measures the reactivity of the airways to known concentrations of agents that induce airway narrowing. Negative BCTs
are useful in excluding the diagnosis of asthma more than conrming the diagnosis when a test is positive. Using this technique in research, the magnitude and duration of the eect of
dierent drugs on the airways may be compared. BCTs are oen
referred to as challenges because the airways are challenged with
increasing doses of methacholine, a synthetic derivative of acetylcholine, in a protocolized manner to determine whether there
is a drop in the FEV1. A decrease in the FEV1 of 20% at specied
doses is considered a positive test result.14 e ERS has published
guidelines for methacholine challenge testing to enhance the
safety, accuracy, and validity of the test.
14
Bronchial challenge testing begins by measuring baseline
spirometry parameters to ensure it is safe to conduct the test.
A BCT should not be performed if the FEV1 is <60% of predicted.14 Most BCTs then begin with nebulization of a solution
of phosphate buered saline. is both serves as a placebo to
assess the airway eect of nebulization and establishes baseline
airway function from which the amount of pulmonary function to be reduced is calculated. Aer each dose, spirometry
eorts are performed based on ATS/ERS criteria. e challenge
data are then summarized into a single number, the provocative
dose causing a 20% fall in forced expiratory volume in 1second
(PD20/mcg).
For methacholine, a PD20FEV1 of <6 mcg indicates severe
airway hyperresponsiveness (AHR), 6–25 mcg indicates moderate AHR, 25–100 mcg indicates mild AHR, 100–400 mcg
suggests borderline AHR, and >400 mcg is a normal AHR test
and excludes asthma. During a BCT, patients may experience
transient respiratory symptoms such as cough, shortness of
breath, wheezing, and chest tightness. An inhaled, SABA or
short- acting muscarinic antagonist may be administered to
alleviate symptoms and quicken the return of the FEV1 to the
baseline value. Because BCTs can elicit severe, life- threatening
bronchospasm, trained personnel and medications to treat
severe bronchospasm should be on hand in the testing area.
Exercise Challenge Test
e exercise challenge test is used to conrm or rule out exercise-
induced bronchospasm (EIB) and to evaluate the eectiveness
of medications used to treat or prevent EIB, which occurs usually in patients with normal PFTs who become symptomatic
with exercise. e etiology of EIB is thought to be related to the
cooling and drying of the airways caused by rapid breathing
during exercise.
Exercise tests are usually done with a motor- driven treadmill (with adjustable speed and grade) or an electromagnetically braked cycle ergometer. Heart rate should be monitored
throughout the test, nose clips should be worn, and the room air
should be dry and cool to promote water loss from the airways
during the exercise test. In most patients, symptoms are eectively blocked by use of an inhaled bronchodilator immediately
before beginning exercise or other exertion causing the problem.
Aer obtaining baseline spirometry, the exercise test is started
at a low speed that is gradually increased over 2 to 4 minutes
until the heart rate is 80% to 90% of the predicted maximum or
the work rate is at 100%. e duration of the exercise is age and
tolerance dependent. Children <12 years generally take 6 minutes, while older children and adults take 8 minutes to complete
the test. Aer the exercise is completed, the patient does serial
spirometry at 5- minute intervals for 20 to 30 minutes. FEV1 is
the primary outcome variable. A 10% or more decrease in FEV1
from baseline is generally accepted as an abnormal response,
although some clinicians feel a 15% decrease is more diagnostic of EIB.
15
Six-Minute Walk Test
e six- minute walk test (6MWT) is a test used to measure the
distance a patient can walk on a at, hard surface in 6 minutes.16
e results of the test are used to determine if a patient requires
continuous oxygen at home. e results have also been correlated to a patient’s quality of life and abilities to complete daily
activities. e results of the 6MWT also help predict morbidity
and mortality for patients with congestive heart failure, COPD,
and primary pulmonary hypertension.
17-19
Pulmonary hypertension studies use this test to monitor the ecacy of interventions
with medications.20 Minicase 2 is an example of how a 6MWT is
used to monitor a patient with pulmonary hypertension.
While performing the 6MWT, the patient is educated that
the goal of the test is to walk as far as possible in 6 minutes,
allowing the patient to select the intensity of exercise. Stopping
and resting is allowed during the test. Reference equations for
healthy adults have been published; however, large variations in
the predicted values exist.21 e minimal important dierence
for the 6MWT is 30 meters for adults with chronic respiratory
disease.21 Continuous pulse oximetry is recommended to capture the lowest arterial oxygen saturation (SpO2). e lowest
SpO2 is a marker for prognosis and disease severity. e test is
discontinued if the SpO2 decreases to <80%. Heart rate measurements and heart rate recovery are recorded during the test.
Poorer outcomes have been associated with reduced heart rate
recovery in the rst minute aer the test. Use of the Borg scale
to document dyspnea and fatigue before and aer the 6MWT
has good reliability when determining exercise limitations in
patients with chronic respiratory disease. Practice tests, younger
age, taller height, less weight, male sex, longer corridor length,
and encouragement all improve test results. Unstable angina
and myocardial infarction in the past 3 to 5 days and syncope
and arterial oxygen saturation by pulse oximetry ≤85% are all
contraindications for performing the 6MWT.22 In practice, the
6MWT is also used to assess the amount of oxygen needed with
exertion. Patients with mild- to- moderate pulmonary disease
may have normal oxygen saturation at rest but poor saturation
with exertion. An oxygen saturation of ≤88% indicates the need
for supplemental oxygen.
Carbon Monoxide Breath Test
Carbon monoxide is a poisonous gas emitted from anything
burning, including cigarette smoke. As discussed in the Diffusion Capacity Tests section, CO binds more readily to Hgb
than oxygen, causing increased fatigue and shortness of breath.
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With a simple breath test by a handheld CO meter, the patient
can see how much CO is in the body (parts per million [ppm])
and in the blood (% COHgb). In clinical studies, a result of
≤10 ppm oen denes a nonsmoker; however, in clinical practice, depending on the meter used, the level is usually lower.
A Cochrane Review found no signicant increase in smoking
abstinence rates with CO measurements.
23
Testing exhaled CO is a simple breath test in which the
patient holds his or her breath for 15 seconds and then exhales
into a meter. e meter is able to indicate how much CO is in the
patient’s lungs and estimate how much is attached to Hgb in the
patient’s blood. e test is an objective value in which patients
can visually see the eects of inhaling smoke when higher values
of CO are detected. Aer 8 to 12 hours without smoking, CO
levels become undetectable.
Fractional Exhaled Nitric Oxide
Measurement of exhaled concentrations of nitric oxide is a noninvasive biomarker test of airway inammation for both diagnosing and monitoring eosinophilic airway inammation.24
Various handheld devices using the patient’s breath are available that include an electrochemical sensor to determine the
exhaled nitric oxide concentration. Fractional exhaled nitric
oxide (FENO) results of >50 parts per billion (ppb) in adults
and >35 ppb in children younger than 12 years indicate eosinophilic inammation with a high likelihood to respond to corticosteroids and certain add- on biologic asthma treatments.
a monitoring test, FENO results are best interpreted as changes
from baseline for each patient rather than using population
normal readings. FENO measurements have many confounding factors, including smoking history, age, and sex. e test
should be used in context with the patient history and as a tool
with other diagnostic and monitoring tests.
25,26
As
presence of obstructive lung disease. Lung volumes determine
the presence of restrictive lung disease, and the diffusion capacity test ascertains the adequacy of gas exchange.
2.
Why is spirometry an important test in the diagnosis of
COPD?
ANSWER: In COPD, postbronchodilator spirometry is necessary
to determine the presence of persistent airow limitation and
the degree of disease severity. In the absence of COPD, other
causes of symptoms should be considered. Physical exam and
history alone are often not adequate to detect airow limitation. Therefore, an objective test with spirometry is needed to
conrm a clinical suspicion.
3.
Does a signicant bronchodilator response on spirometry
testing differentiate as thma from COPD?
ANSWER: Traditionally, reversibility after bronchodilator use
was considered a criterion to differentiate asthma and COPD.
However, evidence has shown that a signicant bronchodilator
response is common in COPD as well, and this assessment is no
longer used to differentiate between asthma and COPD. It is
still a useful test when used in conjunction with a clinical history
(eg, risk factors for COPD, presentation of shortness of breath,
evidence of atopy), physical exam, and other PFTs to support a
clinical suspicion of asthma and/or COPD.
4. How is restrictive lung disease diagnosed?
ANSWER: It is important to note that spirometry only can
provide evidence consistent with restrictive disease, such as a
decrease in FEV1 and FVC with a normal or elevated FEV1/FVC
ratio. However, restriction is a decrease in lung volume as dened
by a decrease in the TLC, which is obtained by lung volume tests,
such as body plethysmography. Test results are needed to diagnose restrictive lung disease.
SUMMARY
is chapter discusses the importance of pulmonary function
testing as it relates to the diagnosis, treatment, and monitoring of respiratory disease states. Aer a review of the anatomy
and physiology of the lungs, the mechanics of obtaining PFTs
were emphasized. By understanding these mechanics, a clinician can better understand the interpretation of PFTs, use
ndings from dierent PFTs to help dierentiate among diagnoses, and assist in making optimal therapeutic recommendations. PFT results are not interpreted in isolation but need
to be assessed within the context of the other ndings from
the medical history and from other laboratory or clinical test
results. Clearly, PFTs are an important tool to aid the clinician
in decision- making.
LEARNING POINTS
1. What is a PFT?
ANSWER: A PFT is any test used to assess the function of the
lungs (eg, spirometry, body plethysmography, 6MWT). The component of the PFT to be ordered is determined by the information needed. For example, spirometry is performed to reveal the
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15
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Liver and Gastroenterology Tests
Paul Farkas, Joanna Sampson, Matthew
Slitzky,and Jason Altman
OBJECTIVES
After completing this chapter, the
reader should be able to
•
Discuss how the anatomy and
physiology of the liver and pancreas
affect interpretation of pertinent
laboratory test results
•
Classify liver test abnormalities
into cholestatic and hepatocellular
patterns and understand the
approach to evaluating patients with
these abnormalities
•
Explain how hepatic and other
diseases, as well as drugs and
analytical interferences, cause
abnormal laboratory test results for
bilirubin
•
Understand hepatic encephalopathy
and the role of serum ammonia in its
diagnosis
•
Discuss the laboratory test
abnormalities typically associated
with hemochromatosis
•
Design and interpret a panel of
laboratory studies to determine if a
patient has active, latent, or previous
viral hepatitis infection
•
Understand the signicance and use
of amylase and lipase in evaluating
abdominal pain and pancreatic
disorders
•
Discuss the role of Helicobacter pylori
in peptic ulcer disease and the tests
used to diagnose it
•
Discuss the tests and procedures
used to diagnose Clostridioides
difcile colitis
Hepatic and other gastrointestinal (GI) abnormalities can cause a variety of clinically
signicant diseases, in part because of their central role in the body’s biochemistry.
is chapter provides an introduction to common laboratory studies used to investigate these diseases. Studies of the liver are roughly divided into those associated with
(1) synthetic liver function, (2) excretory liver function and cholestasis, (3) hepatocellular injury, and (4) detoxifying liver function and serum ammonia. Specic tests
may also be used to investigate specic disease processes, including viral hepatitis,
primary biliary cholangitis (PBC), and hemochromatosis. is chapter also covers
several tests for specic nonhepatic disease processes, including pancreatitis, Helico-
bacter pylori infection, and Clostridioides dicile colitis.
ANATOMY AND PHYSIOLOGY OF THE LIVER
ANDPANCREAS
Liver
e liver, located in the right upper quadrant of the abdomen, is the largest solid
organ in the human body. It has two sources of blood.
1.
e hepatic artery, originating from the aorta, supplies arterial blood rich in
oxygen.
2.
Portal veins carry the venous blood from the intestines to the liver. ey transport
absorbed toxins, drugs, and nutrients directly to the liver for metabolism.
e liver is divided into thousands of lobules (Figure15-1). Each lobule is comprised of plates of hepatocytes (liver cells) that radiate from the central vein much
like spokes in a wheel. Between adjacent liver cells formed by matching grooves in
the cell membranes are small bile canaliculi. e hepatocytes continually form and
secrete bile into these canaliculi, which empty into terminal bile ducts. Subsequently,
like tiny streams forming a river, these bile ducts empty into larger and larger ducts
until they ultimately merge into the common bile duct. Bile then drains into the gallbladder for temporary storage or directly into the duodenum.
e liver is a complex organ with a prominent role in all aspects of the body’s
biochemistry. It takes up amino acids absorbed by the intestines, processes them,
and synthesizes them into circulating proteins, including albumin and clotting factors. e liver is also involved in breaking down excess amino acids and processing
byproducts, including ammonia and urea. e liver plays a similar role in absorbing carbohydrates from the gut, storing them in the form of glycogen, and releasing
them as needed to prevent hypoglycemia. Most lipid and lipoprotein metabolism,
including cholesterol synthesis, occurs in the liver. e liver is the primary location
for detoxication and excretion of a wide variety of endogenous substances produced
by the body (including sex hormones) as well as exogenous substances absorbed by
the intestines (including a panoply of drugs and toxins). us, in patients with liver
failure, standard dosing of some medications can lead to dangerously high serum
concentrations and toxicity. e role of the liver in bilirubin metabolism is explored
further later in the chapter.
DOI 10.37573/9781585286423.015
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