Pulmonary Function Testing

Pulmonary function testing includes

both simple spirometry and
sophisticated physiologic testing.
 Physiology
Normally, the volume and pattern of ventilation
are initiated by neural output from the respiratory
center in the brain stem. This output is influenced by
input from carotid (PaO2) and central (PaCO2, [H+])
chemoreceptors; proprioceptive receptors in
muscles, tendons, and joints; and impulses from the
cerebral cortex. Nerve impulses travel from the
respiratory center via the spinal cord and peripheral
nerves to the intercostal and diaphragmatic muscles.
Normal gas exchange occurs if inspired gas is
transmitted through structurally sound, unobstructed
airways to patent, adequately perfused alveoli.
Normally, alveolar ventilation ( A) and perfusion ( )
are well matched and proportional to the metabolic
rate, and arterial blood gas tensions are maintained
within a narrow range.
 Static Lung Volumes and
Capacities

Static lung volumes reflect the elastic

properties of the lungs and chest wall.
 Vital capacity
Vital capacity (VC or "slow VC") is the maximum
volume of air that can be expired slowly after a full
inspiratory effort. Simple to perform, it is one of the
most valuable measurements of pulmonary function.
Because VC decreases as a restrictive lung disorder
(eg, pulmonary edema, interstitial fibrosis) worsens,
it can be used along with the diffusing capacity to
follow the course of such a disorder and its response
to therapy. The VC also reflects the strength of the
respiratory muscles and is often used to monitor the
course of neuromuscular disorders. (See also the
discussions of maximal voluntary ventilation and
maximal inspiratory and maximal expiratory
pressures, below.)
 Forced vital capacity
Forced vital capacity (FVC), similar to VC,
is the volume of air expired with maximal force. It
is usually measured along with expiratory flow
rates in simple spirometry. The VC can be
considerably greater than the FVC in patients
with airway obstruction. During the FVC
maneuver, terminal airways can close
prematurely (ie, before the true residual volume
is reached), trapping gas distally and preventing
its measurement by the spirometer.
 Total lung capacity

Total lung capacity (TLC) is the total

volume of air within the chest after a
maximum inspiration.
 Functional residual capacity
Functional residual capacity (FRC) is the volume
of air in the lungs at the end of a normal expiration
when all respiratory muscles are relaxed.
Physiologically, it is the most important lung volume
because it approximates the normal tidal breathing
range. Outward elastic recoil forces of the chest wall
tend to increase lung volume but are balanced by the
inward elastic recoil of the lungs, which tends to reduce
it; these forces are normally equal and opposite at
about 40% of TLC. Loss of lung elastic recoil in
emphysema increases FRC. Conversely, the increased
lung stiffness in pulmonary edema, interstitial fibrosis,
and other restrictive disorders decreases FRC.
Kyphoscoliosis leads to a decrease in FRC and in other
lung volumes because a stiff, noncompliant chest wall
restricts lung expansion.
 Inspiratory capacity

Inspiratory capacity is the difference

between TLC and FRC.
 Residual volume and expiratory
reserve volume
The FRC has two components: residual volume (RV),
the volume of air remaining in the lungs at the end of a
maximal expiration, and expiratory reserve volume (ERV);
ERV = FRC - RV. The RV normally accounts for about 25%
of TLC. Changes in RV parallel those in the FRC with two
exceptions: In restrictive lung and chest wall disorders, RV
decreases less than do the FRC and TLC, and in small
airways disease, premature closure during expiration leads to
air trapping, so that the RV is elevated while the FRC and
FEV1 remain close to normal. In COPD and asthma, the RV
increases more than the TLC does, resulting in some
decrease in the VC. The characteristic abnormality seen in
obesity is a decreased ERV, caused by a markedly
decreased FRC with a relatively well-preserved RV.
Dynamic Lung Volumes and
Flow Rates

Dynamic lung volumes reflect the

caliber and integrity of the airways.
Spirometry records lung volume against
time during an FVC maneuver
Forced expiratory volume in 1 sec
Forced expiratory volume in 1 sec (FEV1) is
the volume of air forcefully expired during the first
second after a full breath and normally accounts for
> 75% of the FVC. This value is recorded both as an
absolute value and as a percentage of the FVC
(FEV1 %FVC). The mean forced expiratory flow
during the middle half of the FVC (FEF25-75%) is the
slope of the line that intersects the spirographic
tracing at 25% and 75% of the FVC. The FEF25-75% is
less effort-dependent than the FEV1 and is a more
sensitive indicator of early airway obstruction.
 Prolongation of expiratory flow rates is
increased by bronchospasm (in asthma), impacted
secretions (in bronchitis), and loss of lung elastic
recoil (in emphysema). In fixed obstruction of the
upper airway, flow is limited by the caliber of the
narrowed segment rather than by dynamic
compression, resulting in equal reduction of
inspiratory and expiratory flow rates.
In restrictive lung disorders, increased tissue
elastic recoil tends to maintain the caliber of the
larger airways so that at comparable lung volumes,
flow rates are often higher than normal. (Tests of
small airways function, however, may be
abnormal.)
 Retesting pulmonary function after the patient
inhales a bronchodilator aerosol (e.g., albuterol,
ipratropium) provides information about the
reversibility of an obstructive process (i.e., the
asthmatic component). Improvement in FVC or
FEV1(L) of > 15 to 20% is usually considered a
significant response. In patients with airway
obstruction, absence of a response to a single
exposure to a bronchodilator, however, does not
preclude a beneficial response to maintenance
therapy. In bronchoprovocation testing, a significant
decrease in flow rates after inhaling methacholine
(a cholinergic drug) may indicate asthma.
 Maximal voluntary ventilation
Maximal voluntary ventilation (MVV) is
determined by encouraging the patient to
breathe at maximal tidal volume and
respiratory rate for 12 sec; the volume of air
expired is expressed in L/min. The MVV
generally parallels the FEV1 and can be used
to test internal consistency and estimate
patient cooperation. The MVV can be
estimated from the spirogram by multiplying
the FEV1(L) × 40.
 When the MVV is disproportionately low in a
patient who seems to be cooperating,
neuromuscular weakness should be suspected.
Except in advanced neuromuscular disease, most
patients can generate fairly good single-breath
efforts (e.g., FVC). Because the MVV is much more
demanding, it can reveal the diminished reserves of
weak respiratory muscles. The MVV decreases
progressively with increasing weakness of the
respiratory muscles and, along with maximum
inspiratory and expiratory pressures, may be the
only demonstrable pulmonary function abnormality
in patients with moderately severe neuromuscular
disease.
 The MVV is important preoperatively
because it reflects the severity of airway
obstruction as well as the patient's
respiratory reserves, muscle strength, and
motivation.
 Flow-Volume Loop
The flow-volume loop is generated by
continuously recording flow and volume with an
electronic spirometer during a forced inspiratory and
expiratory VC maneuver. The shape of the loop
reflects the status of the lung volumes and airways
throughout the respiratory cycle. Characteristic
changes occur in restrictive and in obstructive
disorders. The loop is especially helpful in detecting
laryngeal and tracheal lesions. It can distinguish
between fixed obstruction (e.g., tracheal stenosis)
and variable obstruction (e.g., tracheomalacia, vocal
cord paralysis) of the upper airway.
 Lung Mechanics

Airway resistance
Airway resistance (Raw) can be directly
measured with a body plethysmograph,
which determines the pressure required to
produce a given flow. More commonly,
however, Raw is inferred from dynamic lung
volumes and expiratory flow rates, which can
be obtained more easily.
 Maximal inspiratory pressure
and maximal expiratory pressure
Maximal inspiratory pressure (MIP) and
maximal expiratory pressure (MEP) measure the
strength of the respiratory muscles as the patient
forcibly inhales and exhales, respectively, through a
closed mouthpiece attached to a pressure gauge.
Like the MVV, maximal pressures are reduced in
neuromuscular disorders (e.g., myasthenia gravis,
muscular dystrophy, Guillain-Barré syndrome).
These pressures, along with the VC, are often
measured at the bedside of an intubated patient to
predict the success of weaning from ventilatory
support.
 Diffusing Capacity
The diffusing capacity for carbon
monoxide (DLCO) can be determined from a
single breath (DLCOSB). The patient inspires a
known small amount of carbon monoxide
(CO), holds his breath for 10 sec, then
exhales. A sample of alveolar (end-expired)
gas is analyzed for CO, and the amount
absorbed during that breath is then
calculated and expressed as mL/min/mm Hg.
 A low DLCO probably reflects abnormal
ventilation/perfusion ratios ( / ) in diseased lungs
rather than physical thickening of the alveolar-
capillary membrane. However, this test relies on the
avidity of Hb for CO and thus is affected by the
volume of blood and the quantity of desaturated Hb
in the lungs at the time of testing. The DLCO is low
in processes that destroy alveolar-capillary
membranes (eg, emphysema and interstitial
inflammatory or fibrotic processes) and in severe
anemia, in which less Hb is available to bind the
inhaled CO. The DLCO is artifactually low if the
patient's Hb is already occupied by CO (e.g., if he
smokes within several hours of the test). The DLCO
increases with polycythemia and with increased
pulmonary blood flow, as may occur in early heart
failure.
 Small Airways Studies
In the normal lung, bronchi < 2 mm in diameter constitute
< 10% of the total airway resistance, but their aggregate
surface area is large. Disease affecting primarily the small
(peripheral) airways can be extensive yet not affect the Raw
or any tests dependent on it (e.g., FEV1). This is true of early
obstructive lung disease and interstitial granulomatous,
fibrotic, or inflammatory disorders.
The status of the small airways is reflected by the FEF25-
75% and by expiratory flow rates in the last 25 to 50% of the
FVC, best determined from the flow-volume loop. More
sophisticated tests of small airways function have been
devised--e.g., frequency-dependent changes in lung
compliance (dynamic compliance), closing volume, and
closing capacity. In general, such tests add little to those more
readily available and have little place in the clinical laboratory.
Monitoring Respiration During Sleep

Central and obstructive sleep apnea can be

distinguished by monitoring respiration during
sleep. An oximeter on the ear or finger monitors O2
saturation. A catheter placed in a nostril measures
end-tidal PCO2 (PETCO2) and monitors airflow.
Chest wall motion is monitored by a strain gauge or
impedance electrodes. In obstructive sleep apnea,
airflow at the nose ceases despite continued
excursion of the chest wall, O2 saturation drops,
and PETCO2 increases. In central apnea, chest wall
motion and airflow cease simultaneously.
Ordering Pulmonary Function
Tests
As a general preoperative screen,
determination of the FVC, FEV1, FEV1
%FVC, and MVV usually suffices. Testing
should be performed before chest or
abdominal surgery in smokers > 40 yr old
and in patients with respiratory symptoms. In
patients with suspected laryngeal or tracheal
disorders, a flow-volume loop should be
requested. If weakness of the respiratory
muscles is suspected, the MVV, MIP, MEP,
and VC are the appropriate tests.
 A complete set of pulmonary function tests
should be requested when the clinical picture does
not coincide with the data obtained by simple
spirometry or when more complete characterization
of an abnormal pulmonary process is desired. A
complete set includes determination of static and
dynamic lung volumes, DLCO, flow-volume loop,
MVV, MIP, and MEP. However, extensive testing is
tiring, time-consuming, expensive, and
unnecessary for adequate clinical assessment of
most patients. Periodic determinations of VC and
DLCO usually suffice to monitor patients with
interstitial lung disease.
 Measurements of Arterial Blood
Gases
The PaO2 and PaCO2 reflect the adequacy
and efficiency of gas exchange between the
lungs and venous blood. The PaCO2 is
normally maintained in the narrow range of
35 to 45 mm Hg. An increase in CO2
production (CO2) normally results in an
appropriate increase in ventilatory drive and
in alveolar ventilation (A), preventing any
increase in PaCO2. The A and PaCO2 are
inversely proportional at any given level of
CO2 (i.e., A × PaCO2 = k × CO2).
 The PaO2 is considerably lower than the
inspired PO2 (PIO2) and somewhat lower than the
PaO2. The PO2 in inspired gas is calculated as the
fractional percentage of inspired O2 (FIO2) times
barometric pressure (PB). For room air at sea level,
PIO2 = 0.21 × 760 mm Hg ~= 160 mm Hg. As
inspired gas enters the upper airway, it becomes
saturated with water vapor. At sea level and at
normal body temperature (37° C [98.6° F]), water
exerts a partial pressure of 47 mm Hg. After
saturation with water vapor, the PO2 is slightly
diluted; PO2 = 0.21 (760 - 47) ~= 149 mm Hg. For
practical purposes, the PO2 of inspired gas as it
enters the alveoli can be approximated by
multiplying the FIO2 × 7 (e.g., for room air, 21 × 7 =
147 mm Hg; for 40% O2, 40 × 7 = 280 mm Hg).
 Because total gas tension in the alveoli must
remain constant, the greater the amount of CO2
entering the alveoli, the lower the PAO2 must be. In
a patient on a normal diet, the respiratory quotient
(i.e., the ratio CO2/ O2) is not unity but is about 0.8,
thus every 1 mm PACO2 effectively displaces 1.25
mm PAO2. (Respiratory quotient is affected by the
relative quantity of fat and carbohydrate in the diet,
increasing to about 1 with a high-carbohydrate diet
and decreasing to about 0.7 with a high-fat diet.)
For clinical purposes, the PACO2 can be assumed to
equal the PaCO2. Thus, the PAO2 can be calculated
by the equation PAO2 = FIO2 (PB - PH2O) - 1.25
PaCO2.
 For room air, with a PaCO2 of 40 mm Hg, the
PAO2 = 147-50 = 97 mm Hg. Normal A is about 5
L/min, as is perfusion. If A and were perfectly
matched (ie, / = 1), PAO2 and PaO2 would be
equal. The overall / ratio of normal lungs is,
however, about 0.8. This degree of / mismatch
results in a PaO2 that is 5 to 15 mm Hg lower than
the PAO2, equivalent to shunting 2% of pulmonary
arterial (mixed venous) blood directly into the
pulmonary venous circulation without participation
in gas exchange. The difference between PAO2 and
PaO2 (A - aDO2) directly reflects the degree of
mismatching of and, ie, the severity of intrinsic lung
disease.
 The PaO2 for a healthy 20-yr-old breathing room air is
about 90 mm Hg. The normal PaO2 at age 70 is about 75
mm Hg. This physiologic decrease in PaO2 with age results
from a decrease in lung elastic recoil (senile emphysema),
leading to closure of small airways in the tidal volume range,
with a further decrease in the overall / ratio of the lungs.
The physiologic causes of hypoxemia are listed in Table
64-4. A lower-than-normal PIO2 necessarily leads to
hypoxemia, without any alteration in / relationships and
without an increase in the A - aDO2. Passenger cabins of
commercial aircraft are pressurized to the equivalent of an
altitude of 1500 to 2400 m--similar to breathing 17% O2 at
sea level. Hypoxemia can be offset somewhat by
hyperventilation, but a PaO2 as low as 30 mm Hg has been
reported in patients with COPD during commercial flights.
 Hypoventilation alone can lead to hypoxemia, even
without intrinsic lung disease. If the PaCO2 increases from 40
to 80 mm Hg, as might occur with a sedative overdose, the
PaO2 must decrease by 50 mm Hg (i.e., 40 × 1.25), from 90
to 40 mm Hg. When hypoventilation is identified as the main
cause of hypoxemia (i.e., hypoxemia with a normal A -
aDO2), the diagnoses listed in Table 64-4 should be
considered.
By far the most common cause of hypoxemia is /
imbalance. In patients with COPD, loss of tissue elastic
recoil, bronchospasm, and inspissated secretions combine
to worsen / relationships in the lungs. Areas with low /
ratios result in hypoxemia; areas with high ratios lead to
wasted ventilation (dead space), increasing the work of
breathing and contributing to hypercapnia. As long as the
airways are not totally occluded, hypoxemia is readily
corrected with small increments in FIO2, because there is a
strong gradient of diffusion to the areas of alveolar hypoxia.
Characteristically, an FIO2 of 24 to 28% is adequate to
correct hypoxemia due to / imbalance.
 Areas that are not ventilated at all
(because the alveoli are totally collapsed or
filled with fluid) but that are perfused result in
right-to-left shunting of blood. Shunting
results in hypoxemia that is more refractory
to increases in FIO2 because O2 cannot reach
the gas-exchanging surface. Such situations
often require mechanical ventilation and
positive end-expiratory pressure (PEEP) to
increase the FRC and open closed airways.
Impaired diffusion of O2 across the
alveolar-capillary membrane is probably not
a significant cause of resting hypoxemia,
except at high altitude.
 Split-Function
Ventilation/Perfusion Scanning
Preoperative quantitative ventilation/ perfusion
lung scanning (split-function scanning) is a
noninvasive technique useful for predicting
postpneumonectomy lung function. It is most useful
in patients with lung cancer, who frequently have
asymmetric lung function. A radioactive isotope is
injected (perfusion) or inhaled (ventilation) as is
done for a conventional lung scan. After
equilibration, the percentage of isotope in each
lung is determined, usually in the posterior
projection with the patient supine.
 Predicted postpneumonectomy FEV1
equals percentage of radionuclide uptake in
the noncancerous lung multiplied by
preoperative FEV1 (in liters). A value of < 0.8
L (or < 40% of that predicted for the patient)
indicates serious pulmonary disability and
the likelihood of unacceptably high
perioperative morbidity and mortality.
 Transdiaphragmatic Pressure
Measurement
Transdiaphragmatic pressure measurement
permits quantitative assessment of the severity of
diaphragmatic weakness. This procedure can be
used to diagnose bilateral diaphragmatic paralysis.
Balloon manometers are placed in the distal
esophagus and in the stomach, and pressure
across the diaphragm is measured. This procedure
indirectly determines tension in the diaphragm
during an inspiratory effort. Normally, the gradient
across the diaphragm at total lung capacity is > 25
cm of water.
 The diagnosis of unilateral paralysis,
suggested by asymmetric elevation of the
affected hemidiaphragm on x-ray, can be
confirmed by fluoroscopy. During a forced
inspiratory maneuver (the "sniff" test), the
unaffected hemidiaphragm descends
forcefully, increasing intra-abdominal
pressure and pushing the paralyzed
hemidiaphragm cephalad (paradoxical
motion). However, fluoroscopy is
inaccurate for the diagnosis of bilateral
paralysis.
 Exercise Testing
Repeating physiologic measurements during or
after exercise can help determine the relative roles
of heart and lung disorders in the etiology of
dyspnea, assist in disability evaluations, and monitor
the effectiveness of a rehabilitation program.
Patients with suspected asthma but normal resting
exams and spirometry may wheeze during exercise,
especially when inhaling cooled air. A decrease in
VC or FEV1 of > 15% is considered abnormal,
indicating hyperactive airways. A decrease in DLCO
or oxygenation during exercise indicates abnormal
gas exchange and may be the first physiologic
indication of pulmonary vascular or interstitial lung
disease.
 In patients with heart disease, stroke
volume may not increase appropriately
with exercise. Consequently, heart rate
increases disproportionately to the O2--a
result of increased VD/VT (dead space
ventilation), hypoxemia, or fatigue of the
respiratory muscles.