The physiologic basis of spirometry

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Abstract
Spirometry is the most useful and commonly available tests of pulmonary function. It is a physiological test that measures individual inhalation and exhalation volumes of air as a function of time. Pulmonologists and general-practice physicians commonly use spirometry in their offices in the assessment and management of lung disease. Spirometric indices are well validated and easily interpreted by comparison with established normal values. The remarkable reproducibility of spirometry results from the presence of compliant intrathoracic airways that act as air flow regulators during forced expiration. Because of this anatomic arrangement, expiratory flow becomes dependent solely on the elasticity of the lungs and airway resistance once a certain degree of expiratory force is exerted. Insight into this aspect of respiratory physiology can help in the interpretation of spirometry.
Review Article
The Physiologic Basis of Spirometry
Don Hayes Jr MD and Steve S Kraman MD
Introduction
Background
Flow-Volume Curve
Starling Resistor
Equal Pressure Point
Elastic Recoil
Transmural Pressure
Wave Speed Theory
Effort
The Process of Spirometry
Central and Upper Airway Obstruction
Interpretation
Summary
Spirometry is the most useful and commonly available tests of pulmonary function. It is a physi-
ological test that measures individual inhalation and exhalation volumes of air as a function of time.
Pulmonologists and general-practice physicians commonly use spirometry in their offices in the
assessment and management of lung disease. Spirometric indices are well validated and easily
interpreted by comparison with established normal values. The remarkable reproducibility of
spirometry results from the presence of compliant intrathoracic airways that act as air flow reg-
ulators during forced expiration. Because of this anatomic arrangement, expiratory flow becomes
dependent solely on the elasticity of the lungs and airway resistance once a certain degree of
expiratory force is exerted. Insight into this aspect of respiratory physiology can help in the
interpretation of spirometry. Key words: spirometry, physiology, forced expiratory volume, FEV
1
, lung
function, pulmonary function testing. [Respir Care 2009;54(12):1717–1726. © 2009 Daedalus Enter-
prises]
Introduction
In pulmonary medicine, when more than a history and
physical examination is needed to evaluate a complaint of
breathlessness or dyspnea on exertion, the next step is
almost invariably spirometry. Not only can a properly done
and interpreted spirogram aid in diagnosis, but it can help
evaluate the severity of a respiratory problem or impair-
ment and, in many cases, assess response to treatment by
comparing the spirogram performed before and after an
inhaled dose of a bronchodilator. Spirometry requires co-
operation between the subject and the examiner, with re-
sults dependent upon technical factors and patient effort.
The forced vital capacity (FVC), forced expired volume in
the first second (FEV
1
), and the FEV
1
/FVC ratio are very
well standardized and validated after study in groups of
healthy individuals.
1
The relatively small testing variabil-
ity of a properly performed spirogram leads to reliable
Don Hayes Jr MD is affiliated with the Departments of Pediatrics and
Internal Medicine, and Steve S Kraman MD is affiliated with the De-
partment of Internal Medicine, University of Kentucky College of Med-
icine, Lexington, Kentucky.
The authors have disclosed no conflicts of interest.
Correspondence: Don Hayes Jr MD, Departments of Pediatrics and In-
ternal Medicine, University of Kentucky College of Medicine, Lexington
KY 40536. E-mail: ddhaye2@uky.edu.
RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12 1717
detection of air flow abnormalities. The simplicity of spi-
rometry hides the subtleties of the physiologic mecha-
nisms at work, especially the processes that result in air
flow limitation. These phenomena are responsible for the
remarkable consistency of spirometry when it is properly
done. This consistency applies once a certain degree of
effort is made by the subject, and is very difficult or im-
possible to falsify. It results from the flow limitation in-
herent in airway anatomy.
The benchmark studies that described the physiology of
forced expiratory maneuvers used for spirometry were pub-
lished in the 1950s and 1960s. The flow of a forced ex-
piration can be seen as a consequence of the subject’s
muscle strength and airway resistance, as is the case with
a mechanical bellows, but that analogy is seriously incom-
plete because of 2 fundamental structural features of the
respiratory system. First, the lungs are elastic, constantly
exerting an inward force against the stiffer chest wall and
respiratory muscles. Second, the intrathoracic airways are
compressible and subject to intrathoracic pressure gener-
ated by forced expiration. The result of this is that, under
forced expiration, airway resistance is dynamic and changes
with lung volume, effort (transpulmonary pressure), and
air flow. This airway resistance is not evenly distributed,
but occurs at certain points in the airways, because, as air
flows through the airways during forced expiration, the
intraluminal pressure diminishes with distance from the
alveolus, due to the distributed resistance of the airways.
At some point the intraluminal pressure equals the pres-
sure surrounding the airway (the equal pressure point
[EPP]), which will be discussed more extensively later in this
paper. Beyond the EPP or the segment upstream (ie, from the
alveoli to the EPP) the pressure falls below the surrounding
pressure, and the affected airway segment is compressed,
limiting flow. Thereafter, increased effort raises both the driv-
ing pressure and the airway resistance, and the result is that
flow becomes subject only to pulmonary recoil pressure that
is itself dependent on lung volume.
Background
Flow-Volume Curve
In 1958, Hyatt and colleagues published a benchmark
paper that described the functional relationship between
transpulmonary pressure, respiratory gas flow, and degree
of lung inflation.
2
The authors introduced the flow-volume
curve and a simple means of defining maximal expiratory
flow relating to lung volume. They showed that, over the
upper half of the vital capacity (VC), the relationship be-
tween maximal expiratory flow and degree of inflation
was effort-dependent, and over the lower half of the VC,
the relationship was determined by physical properties of
the lower airways, termed the
flow-volume (
FV) curve.
2
The
FV curves produced by the normal subjects and
cardiac patients identified similar measurements at differ-
ent points, without variation.
2
However, the curves pro-
duced by the patients with emphysema demonstrated vari-
ability that correlated with clinical status,
2
thus consistent
with worsening airway obstruction in the clinical setting of an
acute chronic obstructive pulmonary disease exacerbation.
In 1960, Fry and Hyatt demonstrated that the
FV curve
is relatively unaffected by a marked increase in upper
airway resistance in normal subjects.
3
They reported that
the basic element of 3-dimensional graphic representations
of pulmonary ventilation mechanics was the isovolume
pressure-flow curve.
3
Figure 1 illustrates the isovolume
pressure-flow curves obtained by the authors in relation to
flow, volume, and pressure on a 3-dimensional coordinate
system. This 3-dimensional representation included
transpulmonary pressure, respiratory flow, and lung infla-
tion.
3
The
FV curve was easily obtainable and reproduc-
ible, moderately dependent upon effort, essentially unaf-
fected by wide variations in upper airway resistance,
determined by the physical properties and dimensions of
the intrathoracic pulmonary system, and greatly altered in
emphysematous subjects.
3
Starling Resistor
Two studies identified evidence that the driving pres-
sure for expiratory air flow from the lungs is the difference
between alveolar and mouth pressures (P).
3,4
At constant
lung volumes, the expiratory flow rate increases as P
increases, until a critical pressure (P) is reached, at which
point expiratory flow rates are at their maximum.
3,4
In
1967, Pride and colleagues further expanded on these prin-
ciples and reported a method of simultaneously measuring
alveolar pressures and expiratory air flow at constant lung
volume.
5
Expiration was interrupted in subjects at a se-
lected lung volume, and then the subject increased alveolar
Fig. 1. Isovolume pressure-flow curves placed on a 3-dimensional
coordinate system with flow in L/s, volume in L above residual vol-
ume, and pressure in cm H
2
O. (From Reference 3, with permission.)
THE PHYSIOLOGIC BASIS OF SPIROMETRY
1718 RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12
pressures by an effort against a closed valve until the
pressure reached a preset level, at which time the valve
was reopened.
5
The pressure at the mouth immediately
before valve opening was measured by a pressure trans-
ducer.
5
When maximum expiratory flow was reached in an
isovolume pressure-flow curve, a “waterfall” or Starling
resistor effect developed in the airways.
5
The term “wa-
terfall” effect is used as an analogy to the concept that the
volume of water going over a waterfall is independent of
the height of the waterfall, so the downstream segment has
no effect. A Starling resistor is a compressible tube sur-
rounded by the same pressure used to drive flow through
the tube. Once the driving pressure reaches a certain point,
an upstream and downstream segment forms that is sepa-
rated by a point of narrowing. Two physiological phenom-
ena are characteristic of this situation: (1) flow becomes
independent of the downstream pressure, leading to this
“waterfall effect” and subsequent collapse, and (2) self-
developed oscillations form in the downstream segment.
Expiratory flow-limitation is an example of the first char-
acteristic, and snoring seen in obstructive sleep apnea is an
example of the second. Using the waterfall model, simple
equations have been developed to relate the roles of elastic
recoil of the lung, airway resistance, and bronchial col-
lapsibility in determining maximum expiratory flow, air-
way resistance, and P.
5
Equal Pressure Point
In 1967, Mead and colleagues developed a relationship
between static elastic recoil of the lungs and the maximum
rate at which gas is expelled, which they termed the max-
imum flow-static recoil curve.
6
The point where the pres-
sure at the inner wall of the airway is equal to the pleural
pressure was defined as the equal pressure point (EPP).
6
The authors demonstrated that isovolume pressure-flow
curves depict a relationship between pleural pressure and
flow at a particular lung volume, which was previously
described,
2-4
but then they showed how these curves are
interpreted in relation to EPP. During forced expirations,
the authors reported lateral pressures at points within the
airways that equaled pleural pressure, and the pressure
drop from the alveoli to these points approximated the
static recoil pressure of the lungs.
6
This concept of the
flow-limiting segment modeled the intrathoracic airways
as an upstream segment, the alveoli to the EPP, in series
with a downstream segment, the EPP to the mouth. The
distribution of pressures in the airways of the upstream
segment behaved as a Starling resistor, regulating the flow
as expiratory effort varied.
Elastic Recoil
The most important concept to grasp is that forced ex-
piratory flow is not limited by expiratory muscle effort
(once it achieves a certain level), but by the elasticity of
the lungs. In fact, the velocity of exhaled air is determined
by the degree of previous lung inflation and, therefore, the
strength of the inspiratory muscles. This is counterintuitive
because we only feel the active muscle effort associated
with forced exhalation.
To better comprehend this concept, it helps to see the
lung and chest wall as elastic structures balanced against
one another. The lung is stretched in partial expansion,
balanced against the chest wall, which is held in partial
compression (Fig. 2A). If allowed to disconnect from one
another, as in an open pneumothorax, a normal, healthy
lung will spontaneously contract to a size less than resid-
ual volume,
7
expelling its air by the force of the potential
energy stored in its elastic tissue, much like releasing a
stretched rubber band (see Fig. 2B and Fig. 3).
At the same time, the chest wall will spring outward,
without the involvement of muscle activity. With the men-
tal image of reconnecting the lung and chest wall, one can
envision that the lung is stretched on inspiration, storing
elastic energy created by the inspiratory muscles, and then,
Fig. 2. A: Cartoon of lung and chest wall, showing elastic tension
of each (thin, black arrows). The lung is shaded gray. The negative
pleural pressure results from the opposing pull of the chest wall
and lung. It remains negative during passive or mildly forced ex-
piration, as the lung tends to pull in on itself, even as it is allowed
to grow smaller. The situation changes during forced expiration,
as will be shown in Figure 4. The pleural pressure is transmitted
throughout the lung, so that when the pleural pressure is negative
(relative to the air pressure surrounding the body), so is the pa-
renchymal pressure. B: Pleural seal breached allowing lung and
chest wall to assume their un-apposed positions. Pleural pressure
approximates atmospheric pressure.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12 1719
during expiration, allowed to passively retract until it
reaches equilibrium with the passive elasticity of the chest
wall. A deeper breath leads to greater stretch and faster air
flow, which defines quiet breathing but not forced expi-
ration.
One can theorize that forced expiration should over-
whelm the elastic recoil of the lung and force the lung to
empty faster. This concept occurs at high lung volumes,
approximately 80% of vital capacity or higher, and would
be true for the entire expiration if the airways were rigid.
However, they are really quite pliable; even the cartilagi-
nous airways have a membranous portion that, under ex-
ternal pressure, can invaginate, substantially narrowing the
lumen. The smaller airways, imbedded within the paren-
chyma, reduce in size as well, causing expiratory flow to
decrease with lung volume.
At high levels of expiratory effort, the flow-limiting
segments form as illustrated in Figure 4. At the start of an
FVC maneuver, the muscle-generated pressure is applied
to the lung parenchyma and airways, with the airways held
open by the surrounding elastic tissue. As air flow pro-
ceeds toward the mouth, the driving pressure within the
airways is expended, overcoming airway resistance. At
some point, the intraluminal pressure falls below the pres-
sure that surrounds the airway. Beyond this point the in-
volved airways are partially constricted or “choked,” lim-
iting the air flow. This is the Starling resistor effect or
“waterfall,” as previously discussed. Changes in expira-
tory effort will change the position and luminal size of the
choke point, so that extra effort produces extra obstruc-
tion, but air flow remains steady, reflecting only the de-
gree of lung inflation. This variability in resistance is caused
by conditions around the choke point and upstream, to-
ward the lung periphery. Downstream conditions toward
the mouth have no controlling effect on air flow. This is
the reason it has been likened to a waterfall, as there too,
downstream conditions (the height of the waterfall) do not
affect water flow.
Transmural Pressure
In 1975, Jones and colleagues reported the ability to
predict flow during the plateau phase of the flow-volume
curve in a dog model.
8
After deriving an equation so that
maximum flow could be calculated from the area and trans-
mural pressure of the flow-limiting segment, the authors
demonstrated that when maximum flow was kept constant,
the area of the flow-limiting segment varied with trans-
mural pressure.
8
This relationship was confirmed by the
area-transmural pressure curves, which yielded flows iden-
tical to those measured during maximum expiration.
8
The
gradual fall in flow during the plateau phase was due to
flow limitation in more compliant segments located fur-
ther upstream.
8
In another study that same year, also in a
dog model, Jones et al assessed the effect of changing
airway mechanics on maximum expiratory flow, and dem-
onstrated that vagal stimulation resulted in an increase in
small-airway resistance, the EPP moved further toward the
alveoli, and maximum flow was reduced, compared to
control studies.
9
Changes in lung recoil pressure and up-
Fig. 3. Antero-posterior chest radiograph of a man with a complete
pneumothorax of the right lung. Notice the small, airless lung and
increased size of the right chest wall, as shown by the increased
intercostal distance on the side of the pneumothorax (double-
headed arrows).
Fig. 4. Cartoon of chest during forced expiration. Pleural pressure
is now positive, but the air flow through the bronchial tree is reg-
ulated by the choke segments that form when the intra-airway
pressure falls below the surrounding pressure in the lung tissue.
See text.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
1720 RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12
stream resistance were vital in the determination of the
position of EPP as flow accelerates to the peak.
9
Wave Speed Theory
In 1977, Dawson and Elliot further explained the mech-
anism responsible for the flow-limiting behavior of the
choke segment, when they proposed their wave speed the-
ory of flow limitation.
10,11
The basis of their theory is that
a mass flow of a fluid (air, in this case) cannot exceed the
velocity of the pressure differential that drives it (air can-
not flow faster than the speed of sound in the same air).
Dawson and Elliot presented evidence that this mechanism
was operational in airways under conditions of forced ex-
piration. This is not the speed of sound in air as usually
understood (340 m/s), but, rather, the speed of a pressure
wave along the airways, where the compliant airway walls
and air contained in them interact as one physical system.
Because of the airway mass and elasticity, the speed of the
pressure wave is much slower than sound speed in air
alone. The flow rate occurring at wave speed is described
by the following formula:
V
˙
c
A
3
dB
dA
q
1/2
in which V
˙
c is air flow, A is the area of the choke point,
B is the transmural pressure, dB/dA is the stiffness of the
choke segment, q is the correction factor for Poiseuille
flow, and
is the gas density.
Simplifying, we see that the air flow velocity varies
directly with airway cross-sectional area and stiffness, but
negatively with gas density. This makes sense, although
the differential term for choke point stiffness (dB/dA) can-
not be measured in vivo and so is an estimate. Several
researchers have tested this theory and found their results
to be “consistent” with wave speed limitation.
12-16
In 1985,
Webster and colleagues
12
addressed what they thought was
a critical weakness of Dawson and Elliott’s.
11
They pro-
posed a theory describing a mechanism for the dissipation
of energy when effort exceeded what was needed for max-
imal flow. These authors used a 2-dimensional mathemat-
ical model to approximate the physical characteristics of
the trachea, to predict that aerodynamic flutter occurs in
the zone of supercritical flow, as described in wave speed
theory. Such aerodynamic flutter in the supercritical zone
provided a potential means for energy dissipation at max-
imal flow. This also may explain the high-frequency tone
heard with flow limitation.
12
In a canine model, Mink and colleagues demonstrated,
in localized lung disease, that wave speed limitation is
reached in proximal airways if flows from the different
regions are high enough and a choke point occurs more
centrally rather than peripherally; however, if flows are
low, then wave speed is reached peripherally and a choke
point common to all lung regions does not occur.
13
In
1993, in 5 healthy adults, Kano et al tested the hypothesis
that wave speed could be reached at peak expiratory flow
(PEF); they were unable to reject this hypothesis using
maximal forced expiratory effort maneuvers with the neck
fully flexed and extended, after breath-holds at total lung
capacity of 2 seconds and 10 seconds, and with esophageal
pressure measurements, as well as using PEF measure-
ments with a spirometer and pneumotachograph.
14
A
breath-hold at total lung capacity could increase airway
wall compliance by allowing stress-relaxation of the air-
way and reduce the wave speed achievable.
14
In healthy
and asthmatic subjects, Pedersen and colleagues used an
esophageal balloon and a Pitot-static probe positioned in
5 locations between the mid-trachea and right lower lobe
to obtain dynamic area-transmural pressure curves that were
then used to determine wave speed in the central airways
at PEF, but the authors could not exclude that wave speed
is also reached in the more peripheral airways.
15
There remains some controversy, and it is possible that
both flow-limitation theories (choke point and wave speed)
operate together or under different conditions.
17,18
In 1980,
Hyatt and colleagues obtained static pressure-volume
curves and deflation pressure-area curves of the first 3 to
4 airway subsegmental divisions in 9 normal excised hu-
man lungs.
17
They found that the wave speed theory pre-
dicted flow over much of the vital capacity, but other
mechanisms may limit flow at low lung volume. More
recently, using a nonlinear dynamic morphometric model
of respiratory mechanics during artificial ventilation, Bar-
bini et al demonstrated that coupling between dissipative
pressure losses and airway compliance resulted in the on-
set of expiratory flow limitation in normal lungs when
driving pressure was significantly increased with the ap-
plication of subatmospheric pressures to the outlet of the
ventilator expiratory channel.
18
Wave speed limitation re-
mained predominant at even higher driving pressures.
18
Effort
In an important study, Krowka and colleagues demon-
strated a positive relationship between PEF and effort in 5
normal subjects, using flow-volume curves as a noninva-
sive index of expiratory effort with correlation of effort
obtained via esophageal balloon.
19
The investigators then
measured the difference between the largest FEV
1
and the
FEV
1
from the maneuver with the highest PEF during 10
test sessions in 10 normal subjects.
19
The FEV
1
difference
was always 0 mL, with a mean FEV
1
difference of
110 mL for all sessions, which decreased to 80 mL when
the maneuvers with poorly reproducible PEF or FVC val-
ues were discarded.
19
The authors concluded that the FEV
1
is inversely dependent on effort and that maximal effort
THE PHYSIOLOGIC BASIS OF SPIROMETRY
RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12 1721
decreases FEV
1
because of the effect of thoracic gas com
-
pression on lung volume during standard spirometry. The
flow-volume curves of superimposed efforts facilitate the
recognition of submaximal efforts.
19
The Process of Spirometry
The result of these physiologic processes is that, when
done properly, spirometry is remarkably consistent, and
repeated tests will look almost identical (Fig. 5), graphi-
cally confirming adequate effort. One major limitation of
spirometry is its dependence on patient effort, with high
potential for error if effort is suboptimal. Thorough expla-
nation of the procedure to the patient prior to performing
spirometry, followed by active encouragement during it,
will yield more accurate and consistent results. The inter-
preter should recognize if an error is present, and the mag-
nitude of that error. An examination of a flow-volume loop
shows that, after the initial blast, the air flow decreases
smoothly as the lungs empty, reflecting the progressive
decrease in lung elastic recoil and shrinking of the flow-
limiting segments (Fig. 6). A proper effort is nearly always
accompanied by polyphonic wheezes audible at a distance
from the mouth, that are probably generated at the choke
points in the larger airways,
20-22
as they are squeezed to
near closure.
Determining the starting point of the FVC is straight-
forward when the exhalation is optimal, when a volume-
time curve is available, and tidal volume breathing leading
up to the FVC maneuver is displayed. In other situations,
for purposes of timing, the back-extrapolation method is
used to determine the start of the test (Fig. 7). The back-
extrapolation traces back from the steepest slope on the
volume-time curve, as illustrated in Figure 7. To achieve
an accurate time zero and to assure the FEV
1
comes from
a maximal effort curve, the back extrapolated volume must
be 5% of the FVC or 0.150 L, whichever is greater.
23
The traditional way of evaluating the FVC maneuver is
by displaying the volume change against time. The FVC
and FEV
1
can be directly measured from such a plot. The
instantaneous flow at any time on this plot can be esti-
mated from the steepness (rate of change, or slope) of
volume change with time. If this slope itself (in L/s) is
plotted against exhaled volume, then we get a flow-vol-
ume loop, from which flow at any volume can be directly
measured, although time as an independent variable is lost.
This alternative method of examining the FVC is useful
for the easily perceived visual patterns that suggest certain
pathology (Fig. 8).
Central and Upper Airway Obstruction
The effect of central and upper airway (trachea and
above) obstruction on the flow-volume loop depends on
whether the obstruction is within the thoracic cavity (and
therefore subject to intrathoracic pressure changes) or out-
side of it, and whether it is fixed or variable. This creates
3 basic patterns that, in their pure state, are specific to the
Fig. 5. Three superimposed forced vital capacities, demonstrating
the remarkable reproducibility of near maximal efforts.
Fig. 6. Flow-volume loop (left) and volume-time trace (right) of a
healthy subject. This displays the slope of the volume-time trace
with respect to volume. Because time is on neither axis in a flow-
volume loop, time ticks are usually added to show the 1-second,
2-second, and 3-second points. Otherwise, the information is the
same as the volume-time display, although instantaneous flows at
defined volumes are much easier to measure from the flow-vol-
ume loop.
Fig. 7. Back-extrapolation method of determining a reasonable
starting point when initial expiratory effort is suboptimal but the
remainder of the forced vital capacity maneuver is adequate.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
1722 RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12
type and location of the pathology and are easily under-
stood from the physiology involved. A fixed obstruction,
such as is seen with a tracheal stenosis or tumor, will limit
air flow in both directions, whether it is in the chest or
upper airway, and the loop will appear similar in either
case. Flexible or floppy segments, such as those seen in
tracheomalacia, will widen or narrow in response to the
relative pressure differences between the airway lumen
and surrounding tissue, generating either a variable in-
trathoracic or variable extrathoracic obstruction, depend-
ing on the location of involvement. Miller and Hyatt
24
defined 3 classic flow-volume loop patterns that have been
published extensively elsewhere, but we feel this is more
easily understood when shown graphically, as in Figure 9,
where the conditions are idealized for clarity.
There are no actual standard definitions or measure-
ments pertaining to flow-volume loop patterns for the di-
agnosis of central or upper airway obstruction, but there
are several measurements that may predict or suggest it.
Miller and Hyatt
25
described the ratio of the maximum
expiratory flow at the half-way point in the forced expi-
ratory maneuver (MEF
50%
) to the maximum expiratory
flow at the half-way point in the forced inspiratory ma-
neuver (MIF
50%
) to address maximal flow during inspira
-
tion and expiration while performing spirometry, using
interval smaller orifices in the respiratory circuit while
performing a flow-volume loop procedure. The flow dur-
ing the midpoint of inspiration measured at 50% of the
FVC (MIF
50%
or FIF
50%
) is usually greater than the max
-
imal expiratory flow at 50% of the FVC (MEF
50%
or
FEF
50%
), so the MEF
50%
/MIF
50%
ratio is typically 1. In
variable extrathoracic lesions the ratio is increased, while
Fig. 8. Spirometry patterns from patients with restrictive lung dis-
ease and obstructive lung disease. Although the loop patterns on
the left are more visually striking, they do not accurately convey
the relative duration of the efforts; the volume-time tracing shows
that the patient with airways obstruction perseveres for an expi-
ratory time of 19.5 seconds, whereas the patient with restrictive
disease expels his entire vital capacity in little more than 1 second.
Fig. 9. Typical shapes of the flow-volume loop in different kinds of
central or upper airway obstruction. In each panel, the darker seg-
ment of the flow-volume loop indicates the portion of the maneu-
ver depicted above each loop. V
˙
is the flow. V is the volume. The
constricted airway segments are stenotic or floppy tracheal seg-
ments and are not meant to show choke segments, as in Figure 3
(although they look similar here for simplicity). Arrows and signs
indicating pressure changes are omitted to avoid clutter of the
figures. During forced inspiration, intra-airway pressure is lower
than atmospheric pressure, and pleural pressure is lower than
both. During forced expiration, intra-airway pressure is higher than
atmospheric pressure, and pleural pressure is greater than both.
The loops are idealized. In actual patients, some degree of ambi-
guity is often present, so the interpreter must have a high index of
suspicion. Note that patients are often not coached to take a
forceful inspiration, so the inspiratory portion of the loop is often
rather flat, even in healthy subjects. When upper airway obstruc-
tion is suspected, the pulmonary function technician should be
asked to coach both maximal expiratory and inspiratory efforts.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12 1723
in variable intrathoracic lesions the ratio is diminished,
at 0.2.
26
Empey used this same technique of reducing the orifice
diameter to demonstrate that an increased ratio of FEV
1
to
PEF was highly suggestive of central or upper airway
obstruction, with the FEV
1
/PEF index required value be
-
ing 10 mL/L/min.
27
Using these small orifices inserted
into mouthpieces of patients without upper airway ob-
struction, Empey demonstrated upper airway obstruction
in normal patients at an orifice 6 mm in diameter, which
resulted in the FEV
1
/PEF index 10 mL/L/min required
to develop upper airway obstruction; all patients with up-
per airway obstruction had a FEV
1
/PEF index 10 mL/
L/min.
27
Rotman and colleagues evaluated yet another ratio; when
the FEV
1
/FEV
0.5
was 1.5, a central or upper airway
obstruction should be considered.
28
The authors compared
patients with upper airway obstruction, defined as obstruc-
tion at or proximal to the carina, to patients with chronic
obstructive pulmonary disease, using measurements ob-
tained via body plethysmography, and demonstrated that 4
values usually distinguished patients with upper airway
obstruction: (1) forced inspiratory flow at 50% of the VC
(FIF
50%
) 100 L/min; (2) the ratio of forced expiratory
flow at 50% of the VC to FIF
50%
(FEF
50%
/FIF
50%
)or
MEF
50%
/MIF
50%
1; (3) FEV
1
/PEF 10 mL/L/min; and
(4) FEV
1
/FEV
0.5
1.5.
28
In our opinion, spirometry occupies a status similar to
that of auscultation. They are both mature, well estab-
lished techniques that have changed little over many de-
cades. Although simple to perform, their value relies crit-
ically on the experience and knowledge of the operator.
Like auscultation, spirometry evaluates lung function rather
than structure, and so effectively complements imaging
techniques. A working knowledge of the determinants of
flow limitation is helpful in interpreting spirometry.
Interpretation
First and foremost in the performance and interpretation
of spirometry is the issue of test accuracy and quality. The
American Thoracic Society (ATS) and the European Re-
spiratory Society (ERS) published standard recommenda-
tions on spirometric technique and lung function testing in
2005.
29
Avoidance of spirometric testing is recommended
within 1 month of a myocardial infarction or in patients
with chest or abdominal pain, oral or facial pain exacer-
bated by a mouthpiece, stress incontinence, or dementia or
confused state.
29
The goal of tests is to obtain accurate
results that are in agreement between the measurement
result and the actual true value. Reproducibility is vital to
achieve accurate measurements, so individual measure-
ments should be obtained under the same conditions, in-
cluding same method, same instrument, same observer,
same location, same condition of use, and repeated over a
short period of time.
29
As stated in the introduction, the FVC and FEV
1
, along
with their respective ratios, are the best validated param-
eters derived from the spirogram. Innumerable measure-
ments can be made from the time-volume curve and flow-
volume loop, and many have been evaluated in an attempt
to find better indices of lung function or indicators of
small airway disease. Table 1 lists most of the parameters
that have been formally studied. The subject of small air-
way disease and the decades-long search for a test to de-
tect it is beyond the scope of this paper, as it involves more
than spirometry. Automated pulmonary function machines
will easily report many of the measurements on this list,
along with predicted normal values. There is little evi-
dence that any of them provide information about the pa-
tient not already evident in FVC and FEV
1
, along with
their respective ratios.
The only exception is the forced midexpiratory flow
rate (FEF
25-75%
), which has undergone the most scrutiny
of any of these “lesser” tests (Fig. 10). Whether it is help-
ful or not remains controversial, even after decades of
research. The reason for this variability is that the failure
to completely empty the lungs will drive the middle half of
the curve toward the portion with the steepest slope and so
increase the value of the FEF
25-75%
even though the FEV
1
would be unaffected so long as the maximal effort lasted
at least 1 second. Despite controversy and years of re-
search, the use of FEF
25-75%
further illustrates the ever-
changing recommendations for spirometry. Fixed standard
Table 1. Common Derived Parameters Generally Reported by
Pulmonary Function Analyzers*
Parameter Description
FVC Forced vital capacity
FEV
1
Forced expired volume in the first second
FEV
1
/FVC
Ratio expressed as a percent of the FVC
FEV
0.5
Forced expired volume in the first half second
(Measurable but not standardized, and of
questionable value)
FEV
6
Forced expired volume in the first 6 seconds (used
as a surrogate for the FVC in patients with
severe airway obstruction and long forced
expiratory time)
FEF
25-75%
Average flow during the middle half of the FVC
(of controversial value in detecting small airway
disease)
PEF Maximal flow during the FVC
V
˙
max50%
Instantaneous flow at 50% of the FVC
V
˙
max75%
Instantaneous flow at 75% of the FVC
*Only the first three are of undisputed utility, as the others have not been studied in as many
diverse large groups as the first three. Clearly, an infinite number of other derived parameters
can be reported for air flows in shorter or longer time periods than the FEV
1
, or instantaneous
flows at any percentage of the FVC, but there is no evidence that this would be of benefit.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
1724 RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12
cutoffs are no longer recommended, especially with age,
ethnic, and sex differences.
30
In regards to using the FEF
25-
75%
, we recommend not using it, but many clinicians do. If
the FEF
25-75%
is used for clinical care, we suggest using it
for trends rather than true diagnostic purposes.
The ATS established the first statement regarding stan-
dards at the Snowbird workshop in 1979,
31
with subse-
quent updates to these standards in 1987
32
and 1994.
33
The
first initiative for spirometry standardization in Europe
was formulated by the European Community for Steel and
Coal in 1983,
34
which was later updated as the official
statement of the ERS on spirometry in 1993.
35
Airway
obstruction is assessed based on the FEV
1
/FVC ratio, with
these previous guidelines recommending a fixed ratio of
70% as the cutoff for normal. More recent recommenda-
tions by the ATS and ERS Task Force
30
discussed the
advantage of using VC rather than FVC; thus, the ratio of
FEV
1
to VC is capable of accurately identifying more
obstructive patterns than its ratio to FVC, since FVC is
more dependent on flow and volume histories, as demon-
strated by Brusasco et al
36
. Celli and colleagues demon-
strated that the use of fixed cutoffs, such as an FEV
1
/FVC
ratio 70% for airway obstruction, tended to markedly
misclassify subjects who were over 50 years of age.
37
The ATS and ERS Task Force thus recommended that
a decrease in a major spirometric parameter, including
FEV
1
, VC, and FEV
1
/VC, below their relevant 5th per
-
centiles is consistent with a pulmonary defect.
30
Problems
develop when these parameters lie near to the upper and
lower limits of normal, leading to a failure to describe the
function status, so the authors suggested additional stud-
ies, such as bronchodilator response, diffusion capacity,
gas-exchange evaluation, respiratory muscle strength mea-
surements, or exercise testing.
30
Briefly, a diagnosis of
obstruction requires an FEV
1
/VC ratio of 5th percentile
of predicted, while restriction requires a total lung capacity
of 5th percentile of predicted and a normal FEV
1
/VC
ratio; a mixed defect, where there is coexistence of ob-
struction and restriction, is defined when both FEV
1
/VC
ratio and total lung capacity are 5th percentile of pre-
dicted.
30
If an obstructive defect is determined to be present,
the severity of the obstruction is determined by percent of
predicted of the FEV
1
, as outlined in Table 2
.
30
The phys-
iological response of the lower airways to a bronchodilator
involves the airway epithelium, bronchial smooth muscle,
inflammatory mediators, and nerve cells, so individual re-
sponses to a bronchodilator can be variable. The ATS and
ERS Task Force recommended to test either a single dose
of bronchodilator agent in a pulmonary function testing
laboratory or after a clinical trial conducted over 2– 8 weeks,
with a defined significant positive bronchodilator response
in percent change from baseline and absolute changes in
FEV
1
and/or FVC being 12% and 200 mL, respectively.
30
It is important to remember that the comparison of pul-
monary function values to the “predicted” values (reported
as percent of predicted) is useful only for persons whose
lung function was unknown before the test in question.
The predicted values are those of healthy populations of
similar age, race, and sex. The percent of predicted values
help the interpreter decide whether the patient significantly
departs from the normal group. In the case of a patient for
whom previous studies exist, subsequent tests should re-
late to the previous ones. For example, a person who suf-
fers a fall in FEV
1
from 110% predicted to 85% predicted,
while technically still within the normal range, is clearly
deteriorating. His or her real normal value is the best pre-
viously recorded. Excessive importance should not be
placed on the predicted values that are inevitably printed
out by most every spirometer.
Other statistical parameters could also be monitored
rather than percent of predicted, including z scores or stan-
dard deviations of spirometric measurements, which can
account for variability. The key factor is to be consistent in
what parameter is monitored. Our suggestion is to follow
the FEV
1
, which is the most repeatable parameter that
changes in both obstructive and restrictive lung diseases.
Fig. 10. Diagram showing how the forced midexpiratory flow rate
(FEF
25-75%
) is measured from a volume-time tracing. Because the
middle half of the expired volume determines the FEF
25-75%
,an
incomplete forced vital capacity maneuver will shift the FEF
25-75%
toward the earlier part of the curve and raise its value, because the
rate of change in expired volume is greatest near the beginning of
the effort.
Table 2. Severity of Spirometric Abnormality, Based on Forced
Expired Volume in the First Second*
Degree of Severity FEV
1
(% of predicted)
Mild 70
Moderate 60–69
Moderately severe 50–59
Severe 35–49
Very severe 35
*As recommended by the American Thoracic Society and European Respiratory Society Task
Force.
22
FEV
1
forced expired volume in the first second.
THE PHYSIOLOGIC BASIS OF SPIROMETRY
RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12 1725
A short-term, 2-point change in the FEV
1
12% percent
of predicted and 0.2 L are usually statistically signifi-
cant and are probably clinically relevant.
30
Changes in the
FEV
1
less than these criteria may be as important, but
depend on the reproducibility of the pre-bronchodilator
and post-bronchodilator results.
30
Summary
The physiologic basis of spirometry includes the mea-
surement of individual inhalation and exhalation volumes
of air as a function of time. This simple lung function
measurement, which has well established normal values, is
very effective and well validated in diagnosing and mon-
itoring upper and lower airway abnormalities, including
numerous lung diseases. This article summarizes the com-
plex respiratory physiology of spirometry, which is depen-
dent on the elasticity of the lungs and airway resistance
and is determined by the degree of expiratory force ex-
erted. Understanding this complicated physiology is very
important in the field of respiratory care and the interpre-
tation of spirometry.
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THE PHYSIOLOGIC BASIS OF SPIROMETRY
1726 RESPIRATORY CARE DECEMBER 2009 VOL 54 NO 12
    • "residual capacity and expiratory reserve volume [16,17,29]. As expiratory flow velocity is dependent on the degree of previous lung inflation due to the elastic properties of the lung [30], lower static lung volumes would subsequently impact on expiratory flows. Our results support such mechanical changes in a longitudinal setting. "
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    Full-text · Article · Dec 2014
    • "First, the decrease in inspiratory muscle strength influenced the forced expiratory flow. Indeed, forced expiratory flow is not limited by expiratory muscle effort but rather by lung elasticity, given that the velocity of exhaled air is determined by the degree of previous lung inflation (Hayes & Kraman, 2009 ). So, as the lungs lose their elastic recoil (as evidenced by the decreases in VC, IRV, and ERV), expiratory flow limitation may have promoted progressive air trapping, leading to the observed decrease in IC and EILV (Johnson et al., 1999; Zaman et al., 2010). "
    [Show abstract] [Hide abstract] ABSTRACT: This study aimed to assess the effects of an extreme mountain ultramarathon (MUM, 330 km, 24,000 D+) on lung function. Twenty-nine experienced male ultramarathon runners performed longitudinally [before (pre), during (mid), and immediately after (post) a MUM] a battery of pulmonary function tests. The tests included measurements of forced vital capacity, forced expiratory volume in 1 s, peak flow, inspiratory capacity and maximum voluntary ventilation in 12-s (MVV12). A significant reduction in the running speed was observed (-43.0% between pre-mid and mid-post; P < 0.001). Expiratory function declined significantly at mid (P < 0.05) and at post (P < 0.05). A similar trend was observed for inspiratory function (P < 0.05). MVV12 declined at mid (P < 0.05) and further decreased at post (P < 0.05). Furthermore, significant negative correlations between performance time and MVV12 pre-race (R = -0.54, P = 0.02) as well as changes in MVV12 between pre- and post-race (R = -0.53, P = 0.009). It is concluded that during an extreme MUM, a continuous decline in pulmonary function was observed, likely attributable to the high levels of ventilation required during this MUM in a harsh mountainous environment.
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    • "Spirometry is the most useful and commonly available test of pulmonary function [1] . Prediction values are available only for conventional lung function devices using the mouth piece. "
    [Show abstract] [Hide abstract] ABSTRACT: Conventional oral spirometry is a commonly used test for respiratory functions. However, the nasal passages are the primary pathway for regulating ventilation and modulating ventilated air. Here, we tested the validity of using the nasal route (nasal spirometry) for the evaluation of respiratory functions. 250 healthy young adults (150 males and 100 females; 17 to 23 years of age) were subjected to two spirometry tests: oral spirometry by using a mouth piece and nasal spirometry by using a face mask. Measurement parameters included: Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume first second (FEV1), FEV1/FVC%, Forced expiratory flow (FEF25/75%). and maximum voluntary ventilation (MVV). In both males and females, only VC was significantly higher in nasal than oral spirometry, while FVC, FEV1, FEV1/FVC % FEF25/75% and MVV were significantly higher in oral than nasal spirometry. Prediction equations for different measurements of nasal spirometry were derived by multiple regression analysis using sex, height, and weight as independent variables. We conclude that nasal spirometry could be a valid procedure which may be more real in expressing normal respiratory functions.
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