Pulmonary Function 1

Pulmonary Function Tests

Objectives
Using simple tests of pulmonary function, the student will be able to:

1. Recognize abnormalities of flow rates and lung volumes.

2. List and describe lung volumes and lung capacities that make up the total lung capacity.
3. Recognize the three basic patterns of functional abnormality, i.e., obstructive, restrictive,
combined.
4. Recognize abnormalities of gas exchange and respiratory muscle function.

Outline
1. Introduction
2. Types of lung function tests
3. Ventilatory capacity
4. Abnormal spirometry
5. Lung volumes
6. Diffusing capacity
7. Maximal respiratory pressures
8. Arterial blood gases
9. Pulse oximetry
10. Practice questions
11. Appendix
12. An algorithm of the interpretation of pulmonary function tests

1. Introduction
Diseases of the respiratory system may affect the function of the chest wall, the respiratory
muscles, the airways, the alveoli or the pulmonary circulation. In order to best evaluate lung
function and define the extent of impairment physiologic tests are required.

Evaluation of pulmonary function is important in many clinical situations, both when the
patient has a history or symptoms suggestive of lung disease, and when risk factors for lung
disease are present, such as cigarette smoking.

It is important that a physician be able to interpret basic pulmonary function tests.

Disturbance of the mechanical properties of the lungs, of ventilation, of the control of
breathing, of the distribution of ventilation to perfusion within the lungs, and of diffusing
capacity can all be measured. Some are simple whereas others are more sophisticated.
Pulmonary Function 2

2. Types Of Lung Function Tests

The major types of lung function tests include:

o tests of ventilatory capacity

o measurement of lung volumes
o measurement of diffusing capacity
o measurement of maximal respiratory pressure (respiratory muscle strength)
o measurement of gas exchange

3. Ventilatory Capacity
Spirometry is the most readily available and most useful pulmonary function test. Common
clinical measurements of airflow are obtained from forced spirometry, a maneuver in which
the subject inspires to TLC and then forcibly exhales to RV. The spirogram can be plotted in
the form of a volume-time curve or as a flow-volume curve.

3.1. Volume versus time curve

A spirometer records the volume of air expelled during the forced expiratory maneuver.
Three measurements are commonly made from a volume-time recording i.e., a spirogram
obtained during such a forced expiratory maneuver:

o the volume of gas exhaled during the first second of expiration (called the forced
expiratory volume in 1 second, or FEV1

o the total volume exhaled (called the forced vital capacity, or FVC), and

o the peak expiratory flow rate (PEFR)

The normal ratio of FEV1 to FVC is approximately 80%. In other words, a person normally
can forcefully exhale out 80% of their vital capacity in the first second.

Volume exhaled versus time curve

Pulmonary Function 3

3.2. Flow Volume Loop

Here flow and volume are recorded simultaneously during maximum inspiration and
expiration. Peak flow rate (PEF) and maximum flows at 25%, 50%, and 75% of vital capacity
(Vmax) are recorded. Note that the shape of the expiratory flow volume curve is different
than that of the inspiratory flow volume curve. This is because of the factor called
dynamic compression of airways during maximum exhalation. Note: lung volume at start
is TLC while lung volume at end of maneuver is RV.

Flow volume loop

4. Abnormal Spirometry
Spirometry should be classified as normal or abnormal, the latter described as showing either
an obstructive or a restrictive pattern.

4.1. Obstructive Spirometry

The FEV1 is the most important spirometric variable for assessment of airflow obstruction.
It declines in direct and linear proportion with clinical worsening of airways obstruction,
and it increases with successful treatment of airways obstruction. The FEV1 should be used
for determining the degree of obstruction (mild, moderate, or severe) and for serial
comparisons when following patients with asthma or COPD.

The measured FEV1 is usually expressed as a percent of the predicted value for
determination of normality. As a rough guideline, the predicted FEV1 for a 50 year-old of
average height is about 4.0 L for a man and 3.0 L for a woman. Patients with severe COPD
generally have an FEV1 less than one liter, while those with moderate COPD have an FEV1
between 1.0 and 1.5 liters. It is unusual for patients with an FEV1 greater than 2.0 L to have
dyspnea due to airflow obstruction.
Pulmonary Function 4

There is usually a very gradual transition between normal function and mild airflow
obstruction. Physiologists have searched for a test that is more sensitive than the FEV1 for
detection of airflow obstruction in its early stages. None has proven better than the index
obtained by dividing the FEV1 by the FVC.

The FEV1/FVC ratio is the fraction (or the percentage, when multiplied by 100) of the vital
capacity that can be exhaled in the first second. As a rough guideline in middle aged
patients, 70 percent is the lower limit of normal for the FEV1/FVC ratio. This ratio should
be used to detect borderline to mild obstruction.

4.2. Restrictive Spirometry

Disorders, that cause reduction of lung volumes (restriction), may be divided into three
groups:

o Intrinsic lung diseases (parenchymal diseases), which cause inflammation or

scarring of the lung tissue (interstitial lung disease) or fill the airspaces with
exudate or debris (eg. acute pneumonitis).

o Extrinsic disorders (extraparenchymal diseases), such as disorders of the chest wall

or the pleura, which mechanically compress the lungs or limit their expansion.

o Neuromuscular disorders, which decrease the ability of the respiratory muscles to

inflate and deflate the lungs (consider as extraparenchymal diseases).

Spirometry is useful in detecting restriction (reduction) of lung volumes, but it rarely helps
in establishing the cause. Both FEV1and FVC are reduced proportionately, however, in
contrast to obstructive spirometry the FEV1/FVC ratio is maintained or may even be
increased.

4.3. Post-bronchodilator spirometry

Administration of a bronchodilator (eg, salbutamol) by nebulization or metered-dose
inhaler (MDI) may be useful if baseline spirometry demonstrates airway obstruction or if
one suspects asthma. There is no absolute contraindication to the administration of a
bronchodilator in an ambulatory patient. Spirometry should be repeated five minutes after
salbutamol.
In a patient with mild to moderate obstruction, an increase in the FEV1 of more than 12
percent and greater than 0.2 L suggests acute bronchodilator responsiveness.
Pulmonary Function 5

5. Lung Volumes

5.1. Lung Volumes

There are four primary lung volumes that do not overlap.
Tidal volume (VT)
-the depth of breathing; the volume of gas inspired or expired during each
respiratory cycle

Inspiratory reserve volume (IRV)

-the maximal amount of gas that can be inspired from the end-inspiratory position
of normal tidal breathing

Expiratory reserve volume (ERV)

-the maximal amount of gas that can be expired from the end-expiratory level of
normal tidal breathing

Residual volume (RV)

-the amount of gas remaining in the lungs at the end of a maximal expiration

5.2. Lung Capacities

There are four capacities, each of which contain two or more volumes.
Total lung capacity (TLC)
-the amount of gas contained in the lungs at the end of maximal inspiration

Vital capacity (VC)

-the maximal amount of gas that can be expelled from the lungs by forceful effort
following a maximal effort to TLC

Inspiratory capacity (IC)

-the maximal volume of gas that can be inspired from the resting expiratory level

Functional residual capacity (FRC)

-the volume of gas remaining in the lungs at the resting expiratory level

Lung volumes and capacities

Pulmonary Function 6

5.3. Reference values for lung volumes

Lung volumes and capacities of healthy individuals, even though they may be of same
age, height, sex and ethnic origin may vary ~ ±20% from the average values (see the
Appendix for how we declare normal).

5.4. Disease and changes in volumes and capacities

FRC: If the lungs are abnormally stiff or the elastic recoil (tendency to retract) is
increased, the FRC will be lower than normal. If on the other hand, the lung's elasticity is
reduced, the lung collapses less readily, and the FRC will be greater than normal
(hyperinflation).

TLC: A decreased TLC may be due to stiff lungs, weak respiratory muscles or chest cage
deformity. An increased TLC is usually due to decreased lung elastance, as in
emphysema.

VC: Changes in vital capacity may be due to pulmonary or extrapulmonary factors.

Pulmonary factors:
 absolute reduction in distensible lung tissue (lung resection)
 increased lung stiffness that limits expansion
 increased RV (inability to empty gas).

Extrapulmonary factors:
 limitation to thoracic expansion
 limitation to descent of diaphragm
 neuromuscular dysfunction (muscle weakness)

Lung volumes and capacities in disease

Measurement of the total lung capacity (TLC) may be helpful when there is a decrease in the vital
capacity. In the setting of chronic obstructive pulmonary disease (COPD) with a low vital capacity,
Pulmonary Function 7

for example, measurement of the TLC can help determine if there is a superimposed restrictive
disorder.

5.5. Measuring lung volumes

Ventilatory function is measured under static conditions for determination of lung volumes
and under dynamic conditions for determination of forced expiratory flow rates. VC,
expiratory reserve volume (ERV), and inspiratory capacity (IC) is easily measured by having
the patient breathe into and out of a spirometer, a device capable of measuring expired or
inspired gas volume while plotting volume as a function of time. However, other volumes,
specifically, RV, FRC, and TLC cannot be measured in this way because they include the
volume of gas present in the lungs even after a maximal expiration.

Two techniques are commonly used to measure these volumes: helium dilution and body
plethysmography. You do not need to know the details of these techniques!

1. Helium dilution technique

In the helium dilution method, the subject repeatedly breathes in and out from a
reservoir with a known volume of gas containing a trace amount of helium. The helium
is diluted by the gas previously present in the lungs (for example, FRC ) and is not
absorbed into the pulmonary circulation. From knowledge of the reservoir volume and
the initial and final helium concentrations, the volume of gas present in the lungs at
the start (FRC) can be calculated. The helium dilution method may underestimate the
volume of gas in the lungs if there are slowly communicating airspaces, such as bullae
in emphysema.

2. Body plethysmography
If there are slowly communicating airspaces, such as bullae in emphysema, lung
volumes can be more accurately measured with a body plethysmograph, a sealed box
in which the patient sits while panting against a closed mouthpiece. Because there is
no airflow into or out of the plethysmograph, the pressure changes in the thorax
during panting cause compression and rarefaction of gas in the lungs and
simultaneous rarefaction and compression of gas in the plethysmograph. By
measuring the pressure changes in the plethysmograph and at the mouthpiece, the
volume of gas in the thorax can be calculated using Boyle's law, where P1V1 = P2V2
(when temperature constant).

6. Diffusing Capacity
Clinical measurement of diffusing capacity of the lung (DL) is frequently used to assess the
functional integrity of the alveolar-capillary membrane, which includes the pulmonary capillary
bed. Diseases that affect solely the airways generally do not lower DL, whereas diseases that
affect the alveolar walls or the pulmonary capillary bed will have an effect on DL. Even though
DL is a useful marker for assessing whether disease affecting the alveolar-capillary bed is
present, an abnormal DL does not necessarily imply that diffusion limitation is responsible for
hypoxemia in a particular patient (as other physiologic reasons may exist).

Carbon monoxide (CO) is the gas that is used for measuring DL as it is difficult to measure
diffusing capacity for oxygen. CO has a similar solubility in blood and tissue as oxygen.
Pulmonary Function 8

Measurement of the single-breath diffusing capacity for carbon monoxide (DLCO) is quick,
safe, and useful in the evaluation of both restrictive and obstructive disease. In the setting of
obstructive disease, the DLCO helps distinguish between emphysema and other causes of
chronic airway obstruction.

In this test, a small concentration of CO (0.3%) is inhaled, usually in a single breath that is held
for approximately 10 s. The CO is diluted by the gas already present in the alveoli and is also
taken up by hemoglobin as the RBC’s course through the pulmonary capillary system. The
concentration of CO in exhaled gas is measured, and DLCO is calculated as the quantity of
carbon monoxide absorbed per minute per mmHg pressure gradient from the alveoli to the
pulmonary capillaries. The value obtained for DLCO depends on the alveolar-capillary surface
area available for gas exchange and on the pulmonary capillary blood volume. In addition, the
thickness of the alveolar-capillary membrane, the degree of V(ventilation) /Q(perfusion)
mismatching, and the patient's hemoglobin level will affect the measurement. Because of this
effect of hemoglobin levels on DLCO, the measured DLCO is frequently corrected to take the
patient's hemoglobin level into account. The value for DLCO, ideally corrected for hemoglobin,
can then be compared with a predicted value, based either on age, height, and gender

6.1. Causes of a High Diffusing Capacity

o increased lung volume
o increase in pulmonary capillary blood volume
o increase in hemoglobin concentration in blood
o blood (Hb) within the alveolar space (fictitious increase)

6.2. Causes of a Low Diffusing Capacity

o normal person with low lung volume or low hemoglobin level
o cigarette smoking, as an increase in CO in blood
o restrictive lung diseases with disordered pulmonary gas exchange
o reduced alveolar or pulmonary capillary surface area, e.g., emphysema and
pulmonary vascular obstruction

7. Maximal Respiratory Pressures

Measurement of maximal inspiratory and expiratory pressures is indicated whenever there is
an unexplained decrease in vital capacity or TLC, and whenever respiratory muscle weakness
is suspected clinically. Maximal inspiratory pressure (MIP) is the maximal pressure that can be
produced by the patient trying to inhale (from a low lung volume) through a blocked
mouthpiece. Maximal expiratory pressure (MEP) is the maximal pressure measured during
forced expiration (with cheeks bulging) through a blocked mouthpiece after a full inhalation.
Repeated measurements of MIP and MEP are useful in following the course of patients with
neuromuscular disorders. The vital capacity may also be followed, but it is less specific and
usually less sensitive.

8. Arterial Blood Gases

The most commonly used measures of gas exchange are the partial pressures of O2 and CO2
in arterial blood, i.e., PaO2 and PaCO2, respectively. These partial pressures do not measure
directly the quantity of O2 and CO2 in blood but rather the driving pressure for the gas in
blood.
Pulmonary Function 9

8.1. Assessment of oxygenation

Normal partial pressure of oxygen in arterial blood is 80-100 mmHg, but decreases with
age. An elevation in PaO2 is due to administration of oxygen or hyperventilation. Low
PaO2 is due to either alveolar hypoventilation or impaired gas exchange.

8.2. Clinical causes of hypoxemia

o right to left intrapulmonary shunt or cardiac shunt
o alveolar ventilation to perfusion imbalance (VA/Q inequality)
o hypoventilation

A useful calculation in the assessment of oxygenation is the alveolar-arterial O2 difference

(PAO2 - PaO2), commonly called the alveolar-arterial O2 gradient (or A - a gradient). This
calculation takes into account the fact that alveolar and, hence, PaO2 can be expected to
change depending on the level of alveolar ventilation, reflected by the arterial PaCO2.
When a patient hyperventilates and has a low alveolar and arterial PCO2, alveolar and
arterial PO2 will rise; conversely, hypoventilation and a high alveolar and arterial PCO2 are
accompanied by a decrease in alveolar and arterial PO2. To determine the alveolar-arterial
O2 difference, the alveolar PO2 (PAO2) must first be calculated. The equation most
commonly used for this purpose, a simplified form of the alveolar gas equation, is as
follows:

P ACO 2
P AO2 = P IO 2 - 0.8

For example, at sea level the partial pressure of oxygen of inspired air (PIO2) would be 150
Hg, assuming a barometric pressure of 760 mmHg and a water vapor pressure of 47
mmHg {0.21 x (760-47)}. Hence the estimated PAO2 would be ~ 100 Hg, assuming PCO2 is
normal at 40 mmHg.

The alveolar-arterial O2 difference can then be calculated by subtracting measured PaO2

from calculated PAO2. In a healthy young person breathing room air, the PAO2 - PaO2 is
normally less than 15 mmHg; this value increases with age and may be as high as 30
mmHg in elderly patients.

8.3. Assessment of CO2 elimination

The adequacy of CO2 elimination is measured by the partial pressure of CO2 in arterial
blood, i.e., PaCO2. A more complete understanding of the mechanisms and chronicity of
abnormal levels of PaCO2 also requires measurement of pH and/or bicarbonate, since
PaCO2 and the patient's acid-base status are so closely intertwined.

PaCO2 is directly related to carbon dioxide production and inversely related to alveolar
ventilation.

PaCO 2  V CO 2 
VA
Thus, if the alveolar ventilation decreases the PaCO2 will rise, called alveolar
hypoventilation. Doubling of the ventilation would halve the PaCO2 , called alveolar
hyperventilation. Normal PaCO2 is 35-45 mmHg.
Pulmonary Function 10

Causes of a rise in PaCO2:

o blunted ventilatory drive
o abnormal respiratory mechanics
- severe airways obstruction
- weak respiratory muscles
o severely deranged lung parenchyma causing VA/Q mismatch

Causes of a depression in PaCO2:

o central stimulation of the respiratory centre due to
- acidemia, or
- hypoxemia, or
- acute/chronic lung disease affecting lung parenchyma, or
- the status of cerebral irritation

9. Pulse Oximeter
Because measurement of PaO2 requires arterial puncture and provides intermittent rather
than continuous data about the patient's oxygenation, it is not ideal for close monitoring
of unstable patients. An alternative method for assessing oxygenation is pulse oximetry.
The pulse oximeter measures oxygen saturation (rather than PaO2) using a probe usually
clipped over a patient's finger. The device measures absorption of two wavelengths of light
by hemoglobin in pulsatile, cutaneous arterial blood. Because of differential absorption of
the two wavelengths of light by oxygenated and nonoxygenated hemoglobin, the
percentage of hemoglobin that is saturated with oxygen, i.e., the SaO2, can be calculated
and displayed instantaneously.

However, the clinician must be aware of the relationship between oxygen saturation and
tension as shown by the oxyhemoglobin dissociation. Because the curve becomes relatively
flat above an arterial PO2 of 60 mmHg (corresponding to SaO2 = 90 percent), the oximeter
is relatively insensitive to changes in PaO2 above this level. In addition, the position of the
curve and therefore the specific relationship between PaO2 and SaO2 may change
depending on factors such as temperature, pH, and the erythrocyte concentration of 2,3-
diphosphoglycerate. The clinician must also remember that the often-used goal of SaO2 ≥
90 percent does not indicate anything about CO2 elimination and therefore does not
ensure a clinically acceptable PaCO2.

Oxyhemoglobin dissociation curve

Pulmonary Function 11

10. Practice Questions

10.1. Pulmonary function studies on a 35 year old woman reveal the following:

Study Result
PaO2 55 mmHg
PaCO2 32 mmHg
FEV1 (% predicted) 50%
FVC (% predicted) 55%
FEV1/FVC ratio 0.90
TLC (% predicted) 55%
DLco (% predicted) 60%

This patient most likely has:

(A) obstructive disease of the lung.

(B) restrictive disease of the lung.
(C) primarily abnormal ventilatory control.
(D) primarily pulmonary vascular disease.
(E) combined obstructive and restrictive disease of the lung

10.2. Pulmonary function studies on a 25 year old woman reveal the following:

Study Result
PaO2 (on room air) 65 mmHg
PaCO2 (on room air) 32 mmHg
FEV1/FVC ratio 0.80
TLC (% predicted) 100%
DLco (% predicted) 60%

This patient most likely has

(A) obstructive disease of the lung.

(B) restrictive disease of the lung.
(C) primarily abnormal ventilatory control.
(D) primarily pulmonary vascular disease.
(E) restrictive disease of the thorax.

11. Appendix:

11.1. Reference values for pulmonary function testing

Correct interpretation of pulmonary function tests requires the use of appropriate reference
values with which the patient's results are compared.

Predicted values of pulmonary function depend upon age, height, gender, and race.
Pulmonary Function 12

Interpretation of pulmonary function tests must take these and other factors into
consideration. In practice, this is usually done by a computer using linear regression equations
(reference equations) for calculation of "predicted values," as determined by published studies
of large numbers of healthy individuals.

Healthy nonsmokers experience a gradual decline in lung function throughout adulthood and
old age, apparently due to slowly developing, very mild, subclinical emphysema.

• The FEV1 falls approximately 30 mL per year.

• The vital capacity (VC) decreases while the residual volume (RV) increases, leaving the TLC intact.
• The diffusing capacity (DLCO) declines linearly with age.

Cigarette smoking (starting during the early teens) is associated with an earlier peak in lung
function and therefore an earlier onset of decline. In addition all of the changes due to aging
are accelerated in susceptible cigarette smokers.

11.2. Upper and lower limits of normality

A traditional rule of thumb was to use 80 percent of predicted as the lower limit of the normal
range (LLN) for most pulmonary function test results.
Pulmonary Function 1

12. An algorithm for the interpretation of pulmonary function tests

Interpreting Pulmonary Function Tests

Spirometry

Reduced FEV
1 Normal FEV
1

FEV1/FVC > 80% FEV1/FVC < 80% Normal ?

non obstructive defe obstructive defect lung volumes asthma

Low Give Low Normal Bronchoprovocati

lung volumes bronchodilator DLco DLco testing
restrictive defect

DLco FEV1 No change PVD NORMAL No change FEV1

improves in FEV
1 in FEV
1 decreases

Normal Low ASTHMA Lung volumes ASTHMA

DLco

Low Low DILD High RV but High RV

TLC & FRC TLC & FRC normal TLC & F TLC & FRC
+ + + +
high RV normal RV Normal LDco Low D
Lco

Reduced CHEST CHRONIC EMPHYSEM

maximal WALL BRONCHITI
Pres DISEASE

NMD

PVD = pulmonary vascular disease; NMD = neuromuscular disease; RV = residual volume;

Pres = respiratory muscle pressures; DPLD = diffuse parenchymal lung disease;