Forced oscillation technique and impulse oscillometry CHAPTER 5

CHAPTER 5
Forced oscillation technique and impulse
oscillometry
H.J. Smith*, P. Reinhold#, M.D. Goldman}
*Research in Respiratory Diagnostics, Berlin, Germany. #Friedrich-Loeffler-Institute, Jena, Germany.
}
David Geffen School of Medicine, University of California, Los Angeles, USA.
Correspondence: H.J. Smith, Research in Respiratory Diagnostics, Bahrendorfer Str. 3, 12555 Berlin,
Germany.
Conventional methods of lung function testing provide measurements obtained during
specific respiratory actions of the subject. In contrast, the forced oscillation technique
(FOT) determines breathing mechanics by superimposing small external pressure signals
on the spontaneous breathing of the subject [1]. FOT is indicated as a diagnostic method
to obtain reliable differentiated tidal breathing analysis. Because FOT is performed
without closure of a valve connected to the mouthpiece, and without maximal or forced
respiratory manoeuvres, it is unlikely that FOT itself will alter airways smooth muscle
tone [2].
FOT utilises the external applied pressure signals and their resultant flows to determine
lung mechanical parameters. These pressure–flow relationships are largely distinct from
the natural pattern of individual respiratory flows, so that measured FOT results are, for
the most part, independent of the underlying respiratory pattern. Therefore, oscillometry
minimises demands on the patient and requires only passive cooperation of the subject:
maintenance of an airtight seal of the lips around a mouthpiece and breathing normally
through the measuring system with a nose-clip occluding the nares. Potential
applications of oscillometry include paediatric, adult and geriatric populations,
comprising diagnostic clinical testing, monitoring of therapeutic regimens, and
epidemiological evaluations, independent of severity of lung disease. Oscillometry is
also applicable to veterinary medicine.
The last two main sections Relevance of oscillometry in clinical practice and
Oscillometry in the clinical pulmonary laboratory emphasise clinical aspects of
application and interpretation of FOT rather than methodological details and
technological solutions, which are discussed in the two sections that follow immediately
below. Clinical application of FOT does not require mastery of the mathematical
infrastructure of the technical methodology, and readers interested in the clinical use of
FOT may find it more useful to begin with these clinical sections and refer subsequently
to methodological and technological details.
Methodology of impulse oscillation technique
The mechanical basis of oscillometry concerns use of external forcing signals, which
may be mono- or multifrequency, and applied either continuously or in a time-discrete
manner. The impulse oscillation technique is characterised by use of an impulse-shaped,
time-discrete external forcing signal.
Eur Respir Mon, 2005, 31, 72–105. Printed in UK - all rights reserved. Copyright ERS Journals Ltd 2005.
72
OSCILLOMETRY: FOT AND IOS
The most useful aspect of applying FOT pressure pulses rather than pseudo-random
noise (PRN) is improved time resolution of the measurement. The impulse oscillation
technique allows measurement of up to 10 impedance spectra per second. This permits a
useful analysis of intra-breath variation in impedance, comparable to that obtained with
mono-frequency applications. However, a disadvantage of such high impulse rates is the
inability to record longer respiratory time constants that may be more informative
concerning respiratory abnormalities. For this reason, the common application of
impulse oscillation utilises recordings of 5 impedance spectra (5 impulses) per second.
An additional benefit of impulse oscillation is the simplicity of the hardware needed to
generate the forced signals, allowing smaller, more efficient electronic and mechanical
structures with minimal power loss.
A unique aspect of applying pulses of pressure to the respiratory system is the fact that
the entire energy of all applied pressure harmonics is applied within a very short time
period. This causes a higher impact to the respiratory system compared with sinusoidal
or PRN applied pressures, and may be perceived by some patients as a slightly
unpleasant respiratory sensation during measurement.
Peculiarities of aperiodic waveforms
The impulse oscillation method applies aperiodic waveforms using an impulse
generator that produces pressure pulses of limited magnitude and 30–40 ms duration.
These pulses define specific amplitudes and phases of the inherent sinusoidal
components. The time-course of such practical pressure pulses applied to the respiratory
system is not a true Dirac-impulse, defined as having virtually infinite magnitude and
infinitesimal time duration, which would provide a continuous spectrum of frequencies
with the same amplitude. Thus, the terms "impulse-shaped" oscillations and "impulse
pressures" are used to indicate realistic practical pressure pulses rather than
mathematically defined impulses.
The short duration of the impulse-shaped waveform itself provides linearity of
pressure and flow signals in the face of within-breath dynamic changes in the respiratory
system. In contrast, the longer time needed with PRN to embed a range of periodic
functions decreases time resolution, resulting in increased noise of calculated impedance
related to any time-dependence of dynamic changes in the respiratory system.
The characteristic feature of any aperiodic waveform is the resulting continuous
spectrum after transformation of its time course into the frequency domain, using a
Fourier integral rather than a Fourier series, in the fast Fourier transform (FFT).
Thus, the advantage of continuous spectra is particularly important in abnormal
respiratory systems with regional nonhomogeneities (fig. 1), where resistance, reactance
and coherence spectra may manifest deviations from the normally smooth and uniformly
continuous spectral courses.
In contrast, spectra resulting from FFT analyses of periodic multifrequency forcing
such as PRN [3] are discontinuous. Discrete values of impedance are obtained with a
frequency resolution determined by the frequencies of the included sinusoidal
components. As a result, the course of such discrete spectra often may require postprocessing to smooth the PRN spectra [3]. To improve interpretation of discrete PRN
spectra, it is common to approximate the overall spectral range by smoothing with linear,
quadratic or logarithmic functions. However, such smoothing inherently diminishes
information contained in characteristic peaks and plateaus of impedance that may
otherwise provide insight into superimposed parallel resonance phenomena, e.g. related
to upper airway constriction.
Impulse power spectra of pressure and flow generated by the impulse oscillometry
73
kPa·s·L-1
H.J. SMITH ET AL.
Rrs
0.5
Xrs
0.3
0.4
0.2
0.3
0.1
0.2
0
Coherence g2 (ƒ)
Regional
nonhomogeneity
ƒres Reactance Xrs(ƒ)
0.9
0.8
Resistance Rrs (ƒ)
0.7
Reactance area (AX)
0.1 -0.1
0 -0.2
g2
1.0
0
5
10
15
20
Frequency ƒ Hz
0.6
25
30
35
0.5
Fig. 1. – Representative data for spectra of respiratory resistance (Rrs(f); ––), reactance (Xrs(f); - - -) and
coherence (c2(f); - – - – ) are plotted, between 3 and 35 Hz, for a normal adult, during forced oscillation using
pulse-shaped forcing generated by the impulse oscillometry system. Resonant frequency (fres) is shown where the
Xrs(f) tracing crosses zero. The shaded area, below zero Xrs and above Xrs(f) tracing between 5 Hz and fres, is
the integral of Xrs(f) from 5 Hz to fres, and is designated the reactance area (AX). Regional nonhomogeneities
may manifest deviations from the normally smooth and uniformly continuous spectral courses.
system (IOS) are shown in figure 2 over a frequency range of 0.1–35 Hz. The energy
distribution provides practical assessment of low (ƒ5 Hz), as well as high (w20 Hz)
frequency ranges, with decreased amplitude at higher frequencies to minimise nonlinearities due to acceleration of the moving air column [4]. Enhanced amplitudes at the
5
Attenuation dB
0
-5
-10
-15
-20
-25
0
5
10
15
20
Frequency ƒ Hz
25
30
35
Fig. 2. – Power spectra of flow (––), and pressure (----), for the discrete pulse-shaped forcing signal generated by
the impulse oscillometry system. Spectra plotted at frequencies 0.1–35 Hz. Pressure and flow power are highest
at 3–20 Hz. Less power is needed at frequencies w20 Hz, because "competing" higher harmonics of the patient’s
respiratory flow are very small at these frequencies.
74
OSCILLOMETRY: FOT AND IOS
lower frequencies limit the influence of higher harmonics of spontaneous breathing
frequencies.
Impulse oscillometry system
The IOS measuring-head (fig. 3) is functionally similar to PRN systems designed for
the determination of input impedance [1, 5–12]. The characteristic feature of the IOS [13]
is the generation of recurrent aperiodic impulse-shaped forcing signals of alternating
direction.
Flow is measured by a Lilly-type heated screen pneumotachograph with a resistance of
36 Pa?s?L-1, providing a common-mode rejection ratio ofw60 dB up to 50 Hz [12, 14, 15]
for the combination of pneumotachograph and flow transducer system. At flow rates
v15 L?s-1 the heated pneumotachograph is linear within 2%. The proximal side of the
pneumotachograph is connected to a pressure transducer. To guarantee suppression of
technical influences and to avoid phase differences, both pressure and flow channels use
matched transducers of the same type, SensorTechnics SLP 004D [16]. Pressure and flow
signals are sampled at a frequency of 200 Hz and digitally converted by a 12-bit
analogue-to-digital converter. Analogue anti-aliasing low-pass filtering is realised by a
fourth-order Bessel filter at a border frequency of 50 Hz, providing a damping at Nyquist
frequency of y75 dB.
Tuning of the IOS impulse generator involves both volume displacement of the
loudspeaker membrane and magnitude of the terminating resistor. The terminal resistor
RS 232 to computer
DSP
Loudspeaker
Impulse generator
Y-adapter
Metal screen
w
flo
lse flow
pu
y
Im ator
ir
sp
Re
Terminal
resistor
Pneumotachograph
(heated)
Flow
transducer
Mouthpiece
Pressure transducer
Fig. 3. – Schematic diagram of the impulse oscillometry system measuring-head and connectors: loudspeaker
enclosure at top, connected to a y-adaptor at one upper arm, an exit for flow with terminal resistor at the
second upper arm and a lower arm connected to the pneumotachograph. A mouthpiece is connected to the
open side of the pneumotachograph. Pulsatile flows generated by the loudspeaker are shown as a lightly shaded
thick line, part of which exits through the terminal resistor and part of which flows through the
pneumotachograph and mouthpiece. The patient’s normal respiratory flow is shown as a shaded thick line from
the mouthpiece though the Y-connector, exiting through the terminal resistor. The resistance of the terminal
resistor is 0.1 kPa?s?L-1 and the deadspace of the Y-connector/pneumotachograph/mouthpiece is y70 mL.
75
H.J. SMITH ET AL.
provides a low-impedance pathway for normal respiratory flow, which, at the same time,
is high enough to minimise loss of energy of superimposed impulses so that sufficient
impulse pressure is transmitted into the respiratory tract. Both components determine
the linear working range of the unit and range of input impedances, which can be
measured to maintain international recommendations [16, 17]. A terminal resistor of
y0.1 Pa?s?L-1, in combination with a volume displacement of 40 mL, which is
accelerated by the loudspeaker membrane in v40 ms, results in maximal peak-to-peak
impulse pressures of 0.3 kPa and minimises interference of underlying higher harmonics
of respiratory frequency that contribute "noise" to the oscillatory pressure and flow
signal [10].
International recommendations for electromechanical performance are maintained in
the IOS by use of advanced transducer technology and global mean spectral data derived
from IOS are generally comparable to those obtained by the pseudo-random noise
method of Làndser [6], Delecourt et al. [8] and Skloot et al. [18].
The measurement is performed as follows: while the subject spontaneously breathes
ambient air via the tubing between mouthpiece and terminating resistor, the loudspeaker
generator transmits brief pressure impulses via Y-adapter, pneumotachograph and
mouthpiece into the respiratory tract; pneumotachograph and pressure transducer
register the composite signals containing breathing activities and the forcing impulse
signal for further processing.
Further processing of digitised impulse data. Flow and pressure channels contain both
the underlying respiratory system flow and pressure, and the superimposed forced
oscillation signals.
By definition, respiratory input impedance is the transfer function or ratio of effective
pressure (Prs) and flow (V9rs), derived from the superimposed forced oscillations, after
being discriminated from underlying respiratory pressure and flow and their harmonics.
In the mathematical sense, all components are considered "complex", characterised by
modulus and phase.
Prs (f )
ð1Þ
Multifrequency input impedance Zrs(f )~ |0
f0 < f ƒf maxg
V rs (f )
|
Discrimination of superimposed forced oscillations from the underlying respiratory
pressure and flow in the IOS is focused on individual impulses, based on pressure and
flow sampling intervals that include both the impulse stimulus and the respiratory
system reaction to the impulse. Figure 4a gives an example of such a sampling
interval for flow.
A "baseline" straight line segment is inserted between the start- and end-points of
separate sample segments of both pressure and flow. The baseline is a simple linear
approximation of the underlying respiratory flow and pressure throughout the single
impulse excitation. Baseline approximation has proved to be a useful and reliable
technique to decrease the respiratory component of the composite signals for pressure
and flow. Spline reconstruction, sinusoidal approximation of underlying respiratory
pressure and flow or high-pass digital filtering were not as useful. Baseline correction and
offset elimination, as can be seen in figure 4b, allow rectangular windowing prior to the
FFT to effectively reduce spectral leakage and improve the signal-to-noise ratio.
Resolution of calculated pressure and flow spectra is increased by adding numerical
zero values to the real sampling points of the corrected primary data segment. This
procedure allows formation of exactly 2n samples, compatible with FFT requirements.
Choice of sampling interval as well as addition of zero values to this interval allow
76
OSCILLOMETRY: FOT AND IOS
Segment 160 ms
0.75
0.50
Approximated
baseline
0.25
0.00
Pulserate 5·s-1
200 ms
-0.25
-0.50
Corrected impulse flow L·s-1
b)
0.0
0.1
0.4
0.2
0.3
0.4
Recording time s
150
Resulting impulse pressure
0.2
0.7
0.6
0.5
75
Reactive response of respiratory system
0.0
-0.2
Duration
of generator
impulse
0
30
0
Baseline
Impulse flow
60
90
Sampling time ms
120
150
Corrected impulse pressure Pa
Amplitude of primary flow L·s-1
a) 1.00
-75
Fig. 4. – a) Primary flow recording. Note that the primary flow includes the patient’s expiratory respiratory flow
with pulses of "loudspeaker flow" superimposed. The dash-dot line shows the linearly approximated respiratory
flow if there were no superimposed pulsatile flow from the loudspeaker included. By referring all pulsatile flow
and with a similar process utilised for the continuous pressure tracing to the approximated baseline, the flow
and pressure related purely to the pulse generated by the loudspeaker, with the patient’s respiratory flow and
pressure subtracted from the total pressure and flow signals, may be derived. b) Corrected impulse tracings of
flow (––) and pressure (----), derived from baseline correction shown in figure 4a, as prepared for input into the
fast Fourier transform. Duration of impulse corresponds to actual movement time of the loudspeaker diaphragm
(y40 ms in duration). Initial flow response of the respiratory system begins almost immediately. After
loudspeaker movement has ended, the respiratory system continues to respond in a "reactive" manner, with
pressure reaching its peak and then declining, while flow falls below baseline, and then gradually returns to
baseline.
adjustment of spectra concerning low-end border frequency as well as numerical
resolution.
To further improve quality of calculated impedance data, impulses that do not fulfill
defined reliability criteria are rejected. The critical segments of respiration are the phase
transitions between inspiration and expiration. At these zero-crossings of pressure and
flow, gradients of pressure and flow versus time are maximal, and the following principles
are implemented to establish reliability. Slopes of baseline corrections for pressure or flow
w0.7 indicate dominance of the underlying respiratory pressure–flow pattern, and the
77
H.J. SMITH ET AL.
impulse is rejected because separation of the superimposed impulse pressure and flow is
not reliable. Absolute peak flow within the impulse segment must exceed 0.02 L?s-1.
Pulses with less flow are rejected because of very small flow values in the denominator of
the input impedance Equation (1) [19] and the resulting mathematical errors. Finally,
impulses that yield negative resistance values at any frequency after FFT are rejected.
Impulse rate and sampling interval. Impulse rate and selected sampling interval effects
on calculated impedance have been evaluated in vitro as well as in calves of comparable
size to adult humans [20, 21]. No significant effect of impulse rate was observed between 1
and 5 impulses per second.
In contrast, different sampling durations led to significantly different low-frequency
respiratory system reactance (Xrs) results. Using 16 sampling points (80 ms) for data
analysis, no useful information was obtained for Xrs ƒ5 Hz. Use of 32 sampling points
(160 ms) per impulse for data analysis provided useful Xrs5 data. However, sampling
durations of 320 ms did not improve impedance results and coherence c2 ƒ5 Hz was
significantly decreased, consistent with deterioration of calculated impedance quality due
to interactions with spontaneous breathing signals. These findings underlie the current
recommendation to use sampling intervals of 32 sampling points per impulse,
corresponding to an optimised impulse rate of either 3 or 5 impulses per second.
Coherence. The coherence function is defined as the square of the cross-power spectrum
divided by the product of the auto-spectra of pressure and flow at any forcing frequency.
Ranging between 0 and 1, it is a measure of the available linearity [22].
jGV 0 P (f )j2
f0 < f ƒf maxg
ð2Þ
GV 0 V 0 (f ):GPP (f )
2
É et al. [6] found that when the coherence c i0.95, PRN impedance data
Làndser
show a coefficient of variation CV%v10%. Subsequently, coherence value thresholds
of 0.9 or 0.95 have been widely used to accept FOT data. However, if methods other
than PRN forcing input signals or data acquisition are used, this original threshold
value of coherence is not applicable. Miller and Pimmel [23] showed that estimated
variance of calculated impedance is a function of coherence and the number of
estimates averaged. Use of pseudo-random noise techniques commonly includes three
measures of impedance of 16 s each [5]. Three replicate measures require coherence c2
w0.9 to yield an estimated standard error of 10%. In contrast, IOS commonly
includes the average of w100 separate FFT analyses and, accordingly, requires less
perfect coherence for the average data to provide an estimated standard error of
v10%. For clinical purposes it is recommended to use a coherence value of c2 i0.6 at
5 Hz for the acceptance threshold, provided that at least 100 FFT analyses are
averaged. Coherence improves as a function of oscillatory frequency to c2 i0.9 at
10 Hz and higher frequencies (fig. 1).
c2 (f )~
Interpretation of oscillation mechanics
Monofrequency oscillations provide a measure of total respiratory impedance (Zrs)
that includes airway resistance, and elastic and inertive behaviour of lungs and chest wall
at one oscillation frequency. In contrast, multifrequency oscillation methods, such as
pseudo-random noise or impulse oscillation provide measures of respiratory mechanical
properties in terms of Zrs, as a function of frequency (f), allowing the recognition of
characteristic respiratory responses at different oscillation frequencies.
78
OSCILLOMETRY: FOT AND IOS
Zrs has been described in engineering terms by so-called "real" and "imaginary"
components. In medical use, preferred terms are resistance (Rrs) and reactance (Xrs),
respectively.
Zrs(f )~Rrs(f )zjXrs(f ) f0 < f ƒf maxg
ð3Þ
|
In contrast to Rrs, concepts of Xrs are not yet widely appreciated, largely because of
greater complexity of reactive parameters, as well as their numerical characteristics.
The present discussion emphasises the importance of consideration of both Xrs as
well as Rrs for interpretation of respiratory mechanical properties.
Most commonly, the oscillation frequency scale utilised for multifrequency oscillation
methods includes about 5–30 Hz [7, 17, 24]. Oscillation frequenciesv5 Hz are affected by
higher harmonics of underlying natural respiratory frequency [25]. Higher oscillation
frequencies are increasingly affected by "shunt" properties of the upper airways [6, 13, 26]
and capacitive impact of face masks [27] when used.
Respiratory resistance
The resistive component of respiratory impedance, Rrs, includes proximal and distal
airways (central and peripheral), lung tissue and chest wall resistance. Normally, central
resistance dominates, depending on airway calibre and the surface of the airway walls,
while lung tissue and chest wall resistance are usually negligible [7, 28].
Rrs may be considered within normal limits if Rrs at 5 Hz (Rrs5) is within ¡1.64 sd of
the predicted value. Rrs5 values between 1.64 and 2 sd above predicted may be considered
minor, w2 sd moderate and w4 sd above predicted severe obstruction.
In previous reports the calculation of per cent predicted has been used. Rrs5 values that
did not exceed 150% predicted, defined in bronchial challenge comparing changes in Rrs5
to a 20% decrease in forced expiratory volume in one second (FEV1) and 50% increase in
airway resistance (Raw), were considered within normal limits [29–31]. However, it is now
recognised that a 20% decrease in FEV1 is a substantial abnormality, and normal limits
for Rrs might be more profitably defined in their own right, without requiring a specific
relationship to arbitrary spirometric criteria.
In healthy subjects, Rrs is almost independent of oscillation frequency [7, 32, 33], but
may increase slightly at higher frequencies due to the upper airways shunt effect [6, 26].
When proximal (central) or distal (peripheral) airway obstruction occurs, Rrs5 is
increased above normal values. The site of airway obstruction is inferred from the
pattern of Rrs, as a function of oscillation frequency, adjusting as necessary for subject
age [2, 25, 34–40]. Proximal airways obstruction elevates Rrs evenly independent of
oscillation frequency [32].
In distal airways obstruction, Rrs is highest at low oscillation frequencies and falls with
increasing frequency. This negative frequency-dependence of Rrs has been explained in
terms of intrapulmonary gas flow redistribution, due either to peripheral pulmonary
nonhomogeneities or to changes in peripheral elastic reactive properties [6, 8, 34, 35]. As
peripheral resistance increases, Rrs becomes more frequency dependent [26, 36–38].
Frequency dependence of Rrs may be a normal finding in small children [39, 40] and may
be greater than in adults in the presence of peripheral airflow obstruction [8].
Respiratory reactance
The reactive component of respiratory impedance, Xrs incorporates the mass-inertive
forces of the moving air column in the conducting airways, expressed in the term
inertance (I) and the elastic properties of lung periphery, expressed in the term
79
H.J. SMITH ET AL.
capacitance (Ca).
1
v~2:p:f f0 < f ƒf maxg
ð4Þ
Xrs(f )~v:I{ :
v Ca
Most importantly, in medicine, it is emphasised that respiratory Ca is not identical to
compliance. The component of Xrs associated with Ca is defined to be negative in
sign. It is most prominent at low frequencies. In contrast, the component of Xrs
associated with inertance is always positive in sign and dominates at higher
frequencies. Thus, interpretation of Xrs is primarily influenced by the oscillation
frequency range under consideration.
Low frequency capacitive Xrs essentially expresses the ability of the respiratory tract to
store capacitive energy, primarily resident in the lung periphery. In both fibrosis and
emphysema this ability is reduced: in fibrosis because of the stiffness of the lung; in
emphysema because of hyperinflation and loss of lung elastic recoil. Distal capacitive
reactance at 5 Hz (Xrs5) manifests increasingly negative values either in restriction or in
hyperinflation. Thus, Xrs5 characterises the lung periphery, but is nonspecific as to the
type of limitation. Additional information is needed to differentiate peripheral
obstruction from peripheral restriction. This is not usually problematic in clinical
practice.
Capacitive and inertive elements have been modelled by a number of authors [2]. Many
simplifications have been attempted that include serial and parallel circuit elements, to
define an approximation of a normal Xrs spectrum with a zero-crossing exactly at
resonant frequency and positive slope throughout. The frequency range utilised in
multifrequency oscillometric forcing signals should allow for determination of the serial
resonance of the respiratory system under investigation [5].
Resonant frequency. Resonant frequency (fres) is defined as the point at which the
magnitudes of capacitive and inertive reactance are equal.
1
v0 :I~ :
v0 ~2:p:f res
v0 Ca
ð5Þ
1
pffiffiffiffiffiffiffiffiffiffi
ð6Þ
:
:
2 p I :Ca
Because fres can vary over a considerable range and, thereby, appear in close
proximity to oscillation frequencies dominated by either capacitative or inertive
properties, this parameter should not be directly interpreted in terms of a particular
mechanical property of the respiratory system. However, it is a convenient marker to
separate low-frequency from high-frequency Xrs. Thus, low-frequency capacitive Xrs
is dominant at oscillation frequencies below fres, while high-frequency inertive Xrs is
dominant at frequencies above fres. In normal adults, fres is usually 7–12 Hz [33]. In
healthy young children, fres is larger than in adults and increases with decreasing age.
In respiratory disease, both obstructive and restrictive impairments of the distal
respiratory tract cause fres to be increased above normal [7, 26, 36]. The relevance of fres is
normally revealed in within-individual trends over time during bronchial or therapeutic
challenge.
f res~
Capacitive spectral range of reactance. Thoraco-pulmonary elasticity is commonly
viewed as a static property, and normally is investigated in the absence of resistive or
inertive mechanical losses. However, in oscillometry, capacitive Xrs is believed to
comprise useful information concerning peripheral airways mechanical properties. In
80
OSCILLOMETRY: FOT AND IOS
practice, determination of peripheral capacitive Xrs is determined at the lowest frequency
that is not highly interfered with by fundamental respiratory frequency and its harmonics
[41]. In the IOS method, Xrs5 is commonly utilised. In children breathing at high
respiratory frequencies, reactance at 10 Hz may be useful [42] in following bronchial and/
or therapeutic challenge.
Interpretation of Xrs5, is clearly different from that of conventional lung function test
parameters and, in particular, lung compliance. One striking feature of Xrs5 is its negative
value. The minus sign is derived from a general definition in natural sciences to
differentiate elastic properties from moments of inertia, the latter of which is always
positive. Therefore, the minus sign simply confirms a relationship with elastic properties.
Definition of abnormality has previously been based on increased negative readings
related to expected normal values of Xrs5. A differencew0.15 kPa?s?L-1 is most definitely
agreed to imply abnormal lung function, independent of Rrs, although abnormal lung
function may be present with smaller differences.
Capacitance versus dynamic pulmonary compliance. Dynamic pulmonary compliance
is derived from the relationship between oesophageal pressure and changes in lung volume
[43]. In contrast, oscillometry assesses the elastic properties of the respiratory system from
the out-of-phase relationship of simultaneously recorded transrespiratory pressure (Prs)
and central flow signals (V9rs), measured from superimposed oscillations and transformed
into Xrs. Therefore, the term capacitance, Ca, an equivalent of capacitive phase
information between the primary signals Prs and V9rs should be used. The frequency range
for such measures is always below fres.
In pulmonary fibrosis, dynamic lung compliance (CLdyn) is decreased below normal. In
a similar manner, oscillometry yields a decreased estimate of Ca, due to negative
displacement of low frequency Xrs. Both dynamic lung compliance and Ca reflect elastic
limitation and they trend together. Previous oscillometry studies have reported less
sensitivity than dynamic lung compliance in the early stages of restrictive disease [7, 17].
In contrast, pulmonary hyperinflation is associated with loss of lung elastic recoil and
increased CLdyn. Because of the loss of lung elastic recoil, peripheral airways are not
supported externally by lung recoil and the resultant partial peripheral airway
obstruction prevents the applied oscillometric signals from reaching peripheral
compliant areas. In this way, loss of lung elastic recoil indirectly causes a decrease in
Ca, with associated increased negative magnitude of low frequency Xrs, [26, 36]. Indeed,
low frequency Xrs is particularly sensitive to pulmonary hyperinflation, and while Rrs5
may be nearly normal or only moderately increased, Xrs5 is highly abnormal [44].
Reactance area. The index designated reactance area (AX) is a quantitative index of total
respiratory reactance Xrs at all frequencies between 5 Hz and fres. The integration of these
negative values of Xrs [45] creates an area between the reactance zero axis and Xrs,
providing an integrative function to include changes in the magnitude of low-frequency
reactance Xrs, changes in fres and changes in the curvature of the Xrs(f)-tracing. It is
represented graphically in figure 1 as the area under the zero axis of the reactance graph
above the Xrs(f) tracing.
fð
res
AX ~
Xrs(f ):df
ð6Þ
5
This integrative index provides a single quantity that reflects changes in the degree of
peripheral airway obstruction and correlates closely with frequency dependence of
resistance [18].
81
H.J. SMITH ET AL.
Inertive spectral range of reactance. During resting breathing at normal respiratory
frequencies, transrespiratory pressure is dissipated in resistive and elastic losses, whereas
inertive pressure losses are negligible [46]. In contrast, during forced oscillation, when
oscillatory frequencies are more than 10-times greater than normal respiratory frequency,
inertance (I) contributes significantly to dissipation of the externally applied pressures [16,
46]. As noted above, the inertive spectral range of Xrs is at frequencies above fres. These
frequencies reflect mechanical properties of the proximal conducting airways. However,
specific clinical interpretation of Xrs in this range is limited due to the wide variety of
influences that may appear in the upper respiratory tract and resultant resonant effects
that may change Xrs unpredictably. Changes in central airway calibre correlate more
strongly with resistive parameters and are less well represented in the inertive spectral
range.
Finally, it should be noted that oscillometric reactance occasionally demonstrates a
low-to-mid frequency plateau in the Xrs (f) tracing, which is suggestive of possible upper
airway obstruction [47–50].
Variability of oscillometric parameters
The majority of oscillometric parameters can usefully be assessed using the coefficient
of variation (CV%). Short-term variability should not exceed 10%, for magnitude of Zrs
and Rrs at frequencies i5 Hz [17]. Variability of Xrs is larger, because of physiological
and numerical characteristics. Xrs can be positive or negative and is commonly close to
zero. As a result, the calculation of CV% is not suitable to estimate the variability of most
of the Xrs values. Therefore, it is recommended to estimate variability of Rrs and Xrs
using standard deviation, 95% percentiles for normally distributed values or calculating
the absolute difference (range) between minimum and maximum of the Xrs parameters
[20, 51].
Methodological versus biological variability. Low methodological variability in
measures of impedance (Zrs) has been shown using physical models with rather high
reproducibility [20].
Biological variability is much more complex and incorporates intra-breath and intraand inter-subject variability. Intra-subject variability of consecutive measurements
within a specified time period, including circadian variability, day-to-day variability and
variability associated with changes in diseased airways has been reported previously [52–
56].
Intra-breath variability is of specific physiological interest. Commonly, Zrs is
determined as an average over a number of consecutive breathing cycles within 15–
30 s. However, flow- and volume-dependence of Rrs and Xrs within each breathing cycle
may be apparent during both inspiration and expiration, and have been shown in a
number of investigations to reflect specific pathophysiological characteristics [57–61].
Special application of impulse oscillometry system to animals
Application of the impulse oscillation technique has been described in different animal
species. The standard IOS device, originally developed for humans, has been validated
carefully in calves aged up to 6 months and weighing 35–150 kg [20, 27, 62] and in pigs
[63, 64]. For large animals, such as horses or adult cattle, a specially designed IOS unit
has been developed, which is capable of analysing larger flow and volume characteristics.
While no data are available in adult bovines, methodological validation and clinical
application of IOS in horses has been reported [65–67] and is still in progress.
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OSCILLOMETRY: FOT AND IOS
Oscillometry in spontaneously breathing conscious animals requires the imposition of
applied pressure signals via a rigid mask. Without correcting measured impedance for the
facemask, the limit of frequencies that can be clinically analysed is v15 Hz. Higher
frequencies are substantially influenced by the capacitance of the facemask itself [27].
The most useful frequency range for clinical evaluation of respiratory impedance
differs in different species, primarily dependent on animal size. The lower the specific
frequency is, the more sensitive the measurements to the periphery of the respiratory
system are. For example, while the resonant frequency is between 5–12 Hz in calves,
depending on body weight, it isv5 Hz in horses. Accordingly, frequencies that reflect the
lung periphery in horses are lower than in calves.
In agreement with results in human medicine, peripheral airway obstruction is
characterised by a marked increase in magnitude of low frequency respiratory reactance
(|Xrs|) and in fres. In addition, the resistance spectrum of Rrs shows increased negative
frequency dependence and increase in low frequency Rrs (v5 Hz). Upper airway
narrowing is characterised by a parallel increase in Rrs at all frequencies with no change
in the frequency dependence of Rrs. No significant changes occur in reactance with upper
(large) airway narrowing.
Relevance of oscillometry in clinical practice
This section offers a perspective on clinical use of the FOT method of determining Zrs
that may be summarised as follows:
1) FOT provides useful clinical information that prominently includes functional
assessment of small, peripheral airway behaviour beyond that available from
commonly used pulmonary function tests (PFT).
2) Because of its sensitivity to peripheral airway function, FOT in its own right, apart
from other PFT results, provides useful guidance in clinical patient management.
3) The prominence of peripheral airway functional assessment provided by FOT
derives both from Xrs as well as Rrs.
4) The importance of Xrs is amplified by recognition of different Xrs-characteristics at
low, i.e. below resonant frequency (vfres), and high (wfres) oscillation frequencies.
The last issue is considered in detail in the foregoing technological sections.
Briefly, it is noted here that original technical descriptions of FOT included calculation
of the magnitude (|Zrs|) and phase (Q) of Zrs, i.e. polar coordinates [1, 5]. This engineering
description gave way to clinical research descriptions of Rrs and Xrs in Cartesian
coordinates. As noted in the technology section, Xrs relates to peripheral airway
properties at oscillation frequencies vfres, and to central conducting airways at
frequencies wfres. The use of the magnitude of Xrs (|Xrs|) rather than Xrs itself in
algebraic manipulation of reactance data is emphasised, because this increases sensitivity
to changes in peripheral airway mechanical properties, as demonstrated later in this
section in reference to previously reported studies.
The section that follows includes discussion of monofrequency, pseudo-random noise
and pulse-shaped pressure oscillations, as these three methods are currently in common
use. The general principles apply to all methods of FOT for the most part where issues
concern specific use of multifrequency rather than monofrequency or IOS rather than
PRN this difference is stated explicitly. Previous published reviews have discussed
theoretical and modeling aspects of FOT [2, 45, 68]. The present discussion does not
include an exhaustive review of clinical research investigations from the Barcelona group
[69–73], Leuven [6, 29, 32, 36, 39, 74–78], London [7, 79–81], Paris [8, 82–86] and
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H.J. SMITH ET AL.
Vandoeuvre-les-Nancy [25, 87–91], which have all helped to provide the essential
infrastructure for clinical application of oscillometry. Instead, the authors focus on
published studies in relation to current work that permit practical establishment of
oscillometry in the routine clinical pulmonary function laboratory. Furthermore,
because the authors have worked more intimately with IOS, illustrative examples of
current work with this technology are included.
The relative advantages of each type of FOT may be summarised by noting that the
simplest form for clinical practitioners is monofrequency sinusoidal pressure application
[2, 68]. Measurement of Rrs with this method is applicable to patients with sleep apnoea
and those using continuous positive airway pressure or mechanical ventilation.
Multifrequency FOT provides further characterisation of respiratory mechanics,
including variation of Rrs and Xrs with oscillation frequency. PRN FOT has been applied
to the description of patients with asthma, bronchitis, emphysema, diffuse interstitial
lung disease and thoracic wall deformities, and to assess bronchial or therapeutic
challenge [6, 29, 32, 36, 74–78]. Multifrequency FOT using PRN imposes a more gentle
forcing signal perturbation than IOS, and has not been noted to provoke
bronchoconstriction. IOS differs from PRN by utilising brief pressure pulses of 30–
40 ms duration. These pulses result in respiratory pressure responses that may be
perceived as a slightly unpleasant respiratory sensation in some subjects. The brief
pressure pulses provide convenient time-trend analyses and within-breath changes of Rrs
and Xrs not available with PRN. IOS is most familiar to the current authors, and
therefore, this and the following section relate current clinical work with IOS to
previously published reports of both PRN and IOS.
The clinical relevance of FOT may be assessed, as with any test of physiological
function, in terms of its utility in diagnosis. Two general approaches are considered: first,
the use of FOT as part of an initial complete diagnostic evaluation, including spirometry,
body plethysmography, and gas distribution and exchange measures; secondly, the use of
FOT as a means of monitoring response to treatment can include both bronchial and
therapeutic challenge.
Summary information is presented here concerning the utility of FOT in assessing
severity of lung disease, degree of airway reactivity, reversibility of airflow obstruction,
and stratification of breathing mechanics between central and peripheral airways.
Current clinical relevance of FOT relates significantly to the broad range of patients
that may conveniently be evaluated. In contrast to standard PFT requiring maximal
coordinated efforts, FOT requires only normal quiet breathing with the lips tightly closed
to avoid airflow leak, and the wearing of a nose-clip. For this reason, children can be
easily studied, often as early as 3 yrs [8, 19, 92–94]. Similarly, elderly subjects, those with
severe airflow obstruction or those with neuromuscular disease who find maximal forced
respiratory efforts difficult to perform are able to breathe normally for FOT testing [95–
98]. Portability of commercial FOT instruments permits lung function testing at the
bedside or, for occupational lung disease studies, at the place of work [18].
FOT places minimal performance demands upon the patient, often described as
passive cooperation. However, the operator must take considerable care with the test
procedure. Because of the freedom offered to patients by simply breathing normally,
moment-to-moment changes in respiratory resistance may be anticipated. Accordingly, a
minimum of three technically acceptable FOT tests of 20–30 s duration or longer should
be performed. The mouthpiece of the FOT instrument must be supported at a position to
ensure maintenance of a neutral relaxed head and neck posture, avoiding body postures
that might affect Zrs. Children should be seated in an appropriately-sized chair to
comfortably support their legs and adults should avoid crossing their legs, which requires
abdominal muscle contraction that may lead to end-expiratory lung volumes below
relaxation volume. Patients should be comfortably relaxed to maintain a constant body
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OSCILLOMETRY: FOT AND IOS
position without muscular effort. In contrast, firm contraction of the facial muscles is
necessary to support airtight closure of the lips about the mouthpiece. It is also desirable
that FOT testing be performed in a quiet examination room, sufficiently far from others
undergoing spirometry so as to be undisturbed by vigorous operator instructions for
spirometry. The operator must review each FOT test immediately to ensure adequate
recording time free of artefacts; a minimum of 20 s of consecutive artefact-free recording
time is advisable. Lack of attention to these fundamental principles may result in highly
variable FOT tests in an individual that are not clinically interpretable. This is not a
troublesome issue in experienced clinical investigators’ laboratories but it is an important
consideration in clinical PFT laboratories who have not previously used FOT.
An important perceived concern about the clinical relevance of FOT is the availability
of a normal database from which to judge results in a particular patient. Published
reports of normative FOT data in children and adults are available, but the number and
size of these studies represent a much smaller normal population than is available for
spirometry [6, 32, 39, 74, 79, 80, 93]. Differences in techniques of FOT and more recently
in mouthpiece design may allow some degree of uncertainty concerning ranges of normal
expected values for both Rrs and Xrs, in both adults and children. Nevertheless, the
similarity of FOT data using monofrequency sine-wave oscillations, PRN or pulseshaped multifrequency FOT over the past four decades supports the acceptance of
clinically useful guidelines at this time. As expected, Rrs and Xrs are dependent on body
size, and recent data suggest the possibility of racial/ethnic differences [99].
It is suggested that concern over precise definition of "normality versus abnormality" in
an individual should not preclude clinical implementation of FOT at this time, because
bronchial and therapeutic challenges are very helpful in assessing airway responsivity. If
initial baseline Rrs/Xrs data do not clearly identify abnormality relative to existing
normative data, retesting after b-agonist inhalation will immediately identify increased
airway responsivity, and sequential studies over time provide similarly useful guidelines
for clinical patient management.
Diagnostic evaluations
The most obvious relationship with other PFT procedures concerns the widespread use
of spirometry. At the outset, it must be emphasised that spirometry measures maximal
forced respiratory efforts, while FOT measures quiet breathing. Accordingly, it is not
appropriate to demand that FOT and spirometric parameters be closely correlated as a
mandatory requirement for FOT to be considered valid. For example, children with
asthma most commonly manifest normal spirometry [100] with no spirometric response
to inhaled b-agonist [42], while they may manifest abnormal baseline FOT parameters
that are responsive to therapeutic challenge [101]. At the other end of the spectrum,
patients with advanced chronic obstructive pulmonary disease (COPD) commonly
manifest marked dynamic airway compression during spirometry with little spirometric
response to pharmacological treatment, but may often manifest significant FOT
responses [45]. For these reasons, use of spirometry to define severity of obstructive lung
disease or receiver-operating characteristic of true sensitivity and specificity of
oscillometry must no longer be considered the optimal standard.
In some patients, spirometry cannot provide optimal clinical information. Patients
with significant neuromuscular disease are unable to provide the motive force needed for
clear interpretation of spirometric results [97, 98]. Patients with lung allograft
transplantation have obvious thoracic wall limitations that preclude truly maximal
respiratory efforts until many months after surgery, during which time it is often not
possible to detect adverse events, such as infection or acute allograft rejection by
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H.J. SMITH ET AL.
spirometry alone. It is common for forced vital capacity (FVC) and FEV1 to increase
over the first 18–26 weeks post-lung transplantation [102]. Despite this apparent
improvement in spirometric parameters, peripheral airway disease, if it occurs, will lead
to substantial worsening of FOT parameters [103] or of gas distribution [104].
Spirometric determination of responses to bronchial or therapeutic challenge may be
limited by the necessary deep inspiration immediately prior to maximal expiration,
allowing for distinctly different FOT responses [105–108]. This disagreement between
spirometric and FOT parameters during bronchial challenge may be readily documented
by IOS during quiet breathing immediately before and after a deep inspiration, which
commonly reveals immediate but transient bronchodilation in asthmatic subjects during
bronchial challenge. Figure 5 illustrates a 70-s recording of tidal breathing and a deep
inspiration with simultaneous display of calculated magnitude of impedance at 5 Hz
(Zrs5) using impulse oscillometry.
Rrs5 in this patient had increased markedly from 0.3 kPa?s?L-1 at baseline to
1.2 kPa?s?L-1 after cumulative inhalation of 0.25, 0.5 and 1.0 mg?mL-1 methacholine,
when FEV1 had changed by only 260 mL from a baseline of 2.73 L. Zrs5 during normal
breathing and following a deep inspiration with relaxed expiration shows that, at the
onset of the IOS test, Zrs5 is much increased, while after an inspiration to maximal lung
volume, there is a marked fall in Zrs5, which gradually "recovers" with time. Since deep
inspiration to maximal lung volume must immediately precede the FEV1 measurement,
patients like the one whose data are shown in figure 5 will manifest FEV1 responses to
methacholine that are altered by the immediate decrease in airway smooth muscle tone
following maximal inspiration [106, 107].
With these caveats it is suggested that FOT can provide useful supplementary
information to spirometry that may not be tightly correlated with spirometric results. To
put such FOT information into proper perspective, it is necessary to review commonly
observed patterns of FOT results in lung disease (primarily airflow obstruction), and in
response to bronchial and therapeutic challenge.
3
Volume L
2
1
0
-1
2.0
Zrs5 kPa·s·L-1
1.6
1.2
0.8
0.4
0.0
0
10
20
30
40
Recording time s
50
60
70
Fig. 5. – Tidal volume and magnitude of respiratory impedance at 5 Hz (Zrs5) plotted as a function of time
during methacholine challenge. First 40 s are resting breathing. After 40 s, subject inspired to total lung
capacity, followed by relaxation back to normal resting breathing. Note that Zrs5 increases markedly during
each exhalation. After the deep inspiration, Zrs5 decreases transiently, with gradual return towards initial levels
over the following 24 s. The moving average of Zrs5 is shown by the dash-dot line.
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OSCILLOMETRY: FOT AND IOS
Oscillometry in relationship to other diagnostic pulmonary functional tests
An important body of work has related FOT to body plethysmography [29, 76–78]. A
group led by Van Noord have reported high correlations between Raw and FOT
parameters in patients with obstructive lung disease and between absolute total lung
capacity (TLC) and FOT parameters in patients with diffuse interstitial lung disease. In
further studies comparing plethysmography, spirometry and FOT to assess reversibility
of airflow obstruction, Van Noord’s group reported the distinctly lower sensitivity of
FOT than plethysmography [77]. The importance of this and other work by the Van
Noord group is discussed further in the following sections.
It is widely recognised that body plethysmographic resistance, Raw includes only the
resistance of the extrathoracic and intrathoracic airways, while Rrs includes that of the
chest wall and lung tissue in addition to airway resistance. Resistance of the chest wall
has been reported [75], but there has been limited clinical interest in this parameter
because of the technical difficulty of the measurements. Another difference between Raw
and Rrs relates to the status of the glottic aperature: it is commonly assumed that the
glottis is maximally open during panting, but Jackson et al. [109] have shown that this
occurs only in totally unrestricted panting. During voluntary attempts to control panting
frequency and tidal volume, there is significant adduction of the vocal cords. Similarly,
during quiet breathing, normal subjects commonly manifest a small, but variable, degree
of vocal cord adduction during expiration. In patients with obstructive lung disease, this
phasic expiratory adduction, visualised during the course of bronchscopy, does not
appear to be systematically different from that observed in normal subjects. Thus, it is to
be expected that average Rrs will differ systematically from panting plethysmographic
Raw.
It is also well established that Raw is more prominently influenced by large airway than
by small airway resistance. Thus, Smith and Dubois [110] reported a comparable increase
in deadspace when compared to the decrease in Raw in response to scopolamine in
normal subjects. In addition, Hensley et al. [111] reported similar changes in Raw and
deadspace after inhaled atropine. These results are consistent with the idea that Raw is
primarily influenced by large airways. In contrast, Rrs is importantly influenced by small
airway resistance, and, accordingly, it may be expected that FOT responses to
interventions that improve peripheral airway obstruction will be more prominent than
Raw responses. Because of the prominent effect of peripheral airway obstruction on FOT
measurements, it may be expected that FOT indices of peripheral airway obstruction
might correlate more closely with indices of gas distribution ("Closing volume" [104]) and
areas of lung hyperinflation manifested by computerised tomography [112] than with
plethysmographic or spirometric indices, although there are no published comparisons at
this time.
Oscillometry as a clinical monitor of response to treatment
By way of summarising the clinical relevance of FOT, it is worth considering the
special value of FOT as a means of monitoring response to interventions. FOT has been
reported to show greater sensitivity to inhaled corticosteroid or to b-agonist inhalation
[8, 113–115] than spirometry. Both inhaled corticosteroids and b-agonists improve small
airways function, and FOT responses manifest prominent changes in indices of
peripheral airway obstruction. In contrast, spirometric sensitivity to small airways
function is less prominent. Accordingly, it is expected that FOT might provide useful
indices of peripheral airway change in response to therapeutic interventions. Such use of
FOT provides a clinically valuable monitoring tool to follow therapeutic changes in small
87
H.J. SMITH ET AL.
airways function over time. This use of FOT for therapeutic monitoring is not dependent
on the use of FOT as an initial diagnostic evaluation.
Finally, as a matter of practical convenience, FOT is more readily utilised in the
clinical pulmonary function laboratory than body plethysmography. This issue is
relevant to recent interest in the therapeutic value of anticholinergics in patients with
COPD. As noted above, anticholinergics result primarily in large airway bronchodilation, and changes in Raw and deadspace are considerable [110, 111]. Thus, effective
airway cholinergic blockade decreases large airway bronchomotor tone and increases
deadspace, with relatively little effect on small peripheral airways disease. Whereas body
plethysmography may be considered a useful technique to monitor such treatment
effects, it is substantially less convenient to use routinely than FOT.
Oscillometry in the clinical pulmonary laboratory
Clinical interpretations of FOT responses in patients have often been related directly
to the application of a particular mechanical or electrical model of the respiratory
system. Van Noord et al. [78] discussed their results in diffuse interstitial lung disease
with respect to an electrical analogue of the respiratory system. They further confirmed
earlier work (vide infra) that ascribed negative frequency dependence of resistance to
peripheral airway obstruction [116, 117]. Engineering models of the respiratory system
have provided predictions of FOT characteristics in normal human subjects, and changes
in FOT parameters in lung disease. However, the fact that many of these predictions have
been observed empirically does not constitute proof of validity of one or other
engineering models. Rather, it provides evidence that under the particular conditions of
the FOT measurements undertaken, the empirical results show patterns that would be
intuitively expected in normal subjects and those with lung disease. Over the past 3
decades, a body of empirical evidence has accumulated that relates FOT results to
particular lung diseases, indeed establishing patterns that are characteristic of lung
disease. The following sections draw heavily upon this clinical research and codify FOT
results with respect to obstructive lung disease, with very limited data in diffuse
interstitial lung disease. These FOT data are not intended as validations of engineering
models, but instead, to illustrate commonly observed patterns of FOT characteristics
associated with lung disease.
Obstructive lung disease
The relationships of FOT to spirometry noted above have a common theme.
Spirometry does not provide a clear indication of peripheral airway obstruction, despite
the general information contained within the shape of the flow–volume curve, and values
of mid-flow rates (forced expiratory flow between 25 and 75% of the forced vital
capacity). Thus, the most striking characteristic of FOT in relation to spirometry is the
relatively greater sensitivity of FOT to peripheral airway disease [2, 18, 25, 29, 32, 42, 45,
52, 68, 82].
Peripheral airway disease. The most well-known FOT result empirically observed in
peripheral airway disease in adults is frequency dependence of resistance (fdr). Grimby
et al. [116], using multiple replicates of monofrequency FOT, were the first to demonstrate
the pattern of frequency dependence, wherein calculated Rrs was greater at 3 Hz than at 5,
7 or 9 Hz in patients with chronic airflow obstruction (CAO). As calculated Rrs decreased
as oscillation frequency increased, patients with CAO might manifest nearly normal
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OSCILLOMETRY: FOT AND IOS
values of Rrs at sufficiently high frequencies. For this reason, Grimby et al. [116] focused
on low (3 Hz) monofrequency Rrs to avoid masking differences between patients with
airflow obstruction and normal subjects [118]. Many subsequent reports [18, 32, 36, 74,
82, 117, 119] confirmed that subjects with early peripheral airways disease, including
smokers, certain industrial workers and normal subjects after histamine infusion,
manifested frequency dependence, even with normal values of low-frequency Rrs in
smokers. Importantly, the abnormal frequency dependence of resistance occurred in the
presence of normal spirometry in those subjects with early peripheral airways disease [18,
32, 117]. This body of clinical research is largely empirical, although it had been shown on
autopsy many years earlier that cigarette smokers who died early in life had manifested
peripheral airway inflammation on autopsy [120]. Similarly, there is now ample evidence
of peripheral airway inflammation in patients with asthma, and, as will be illustrated
below, frequency dependence of resistance occurs prominently in asthma.
The sensitivity of frequency dependence to peripheral airway disease is the first
discriminant between methods of FOT in general: while monofrequency FOT is
convenient to dissect within-breath patterns of change in Rrs [61, 68] or changes in Rrs
during sleep-disordered breathing or in patients on mechanical ventilators [2],
multifrequency FOT is most convenient to document frequency dependence of resistance
in practical use in the clinical pulmonary function laboratory. Monofrequency FOT may
be used at two or more single frequencies; however, multifrequency FOT uses different
oscillation frequencies applied within a single burst to dissect patterns consistent with
peripheral rather than central airway obstruction. This dissection is based upon
established observations that pressure oscillations at frequencies w15 Hz are severely
damped out before reaching peripheral airways, while those at frequencies v10–15 Hz
penetrate much further to the lung periphery [25, 121].
The transition between "large central" airways and "small peripheral" airways is
neither precisely fixed anatomically nor precisely defined in terms of airway lumen
diameter. The illustrations in figures 6 and 7 reflect common patterns observed in
children with asthma and in adults with COPD.
Figure 6 shows representative IOS tests pre- and post-salbutamol in a 6-yr-old patient
Resistance Rrs kPa·s·L-1
1.0
0.8
0.6
0.4
0.2
0.0
0
5
10
20
15
Frequency ƒ Hz
25
30
35
Fig. 6. – Conventional plots of respiratory resistance (Rrs(f)), as a function of oscillation frequency, in a 6-yr-old
child with asthma. Note that frequency axis is shown between zero and 35 Hz, while data are plotted between
3–35 Hz. A vertical dotted line is shown at 5 Hz, the lower limit at which most impulse oscillometry system
data are reported. ––: data prior to nebulised b-agonist bronchodilator; ----: data after bronchodilator.
89
H.J. SMITH ET AL.
Resistance Rrs kPa·s·L-1
1.0
0.8
0.6
0.4
0.2
0.0
0
5
10
20
15
Frequency ƒ Hz
25
30
35
Fig. 7. – Respiratory resistance (Rrs(f)) in an adult patient with chronic obstructive pre- and post-nebulised bagonist bronchodilator. ––: pre-bronchodilator; ----: post-bronchodilator. Note that Rrs(f) is unchanged after
bronchodilator at frequencies w12 Hz.
with mild asthma. Rrs is plotted as a function of oscillation frequency (Rrs(f)-tracing).
Note that prior to b-agonist, Rrs5 is 0.93 kPa?s?L-1. Rrs falls steeply with increasing
oscillation frequency to a minimum at 18 Hz, after which it increases with further
increases in oscillation frequency. While Clement et al. [39] have shown that normal
children manifest a mild degree of frequency dependence, the very large fall in Rrs
between 5 and 15 Hz in figure 6 is consistent with abnormal peripheral airways function
in a 6 yr old. This is confirmed by administration of nebulised b-agonist, after which Rrs5
decreased to 0.59 kPa?s?L-1 (37% change). Note also that the fall of Rrs between 5–15 Hz
post b-agonist is much less than pre b-agonist. Baseline and post b-agonist IOS data in
this child may be compared with data in normal children of this age, who manifested
v15% fall in Rrs from 5–15 Hz [122]. The response to b-agonist in figure 6 may also be
compared with responses of normal nonatopic children who manifested an average
change in Rrs5 after salbutamol of 19% [122]. Finally, it can be seen in figure 6 that Rrs(f)
at frequencies w20 Hz decreased substantially after b-agonist. Adult patients with
asthma show similar findings to those in figure 6. Rrs may be nearly independent of
oscillation frequency in adult asthmatics after beta agonist.
Figure 7 illustrates an adult patient with COPD, pre- and post-b-agonist. In contrast
to asthma, Rrs(f) decreases continuously with oscillation frequency between 5–25 Hz at
baseline, and after b-agonist there is a decrease in Rrs(f) only at low frequencies,v12 Hz.
The findings in figures 6 and 7 are consistent with bronchodilation produced by bagonist in both large and small airways in the asthmatic subjects, but only in small
airways in the patient with COPD. In some patients with COPD who also have reactive
airways, b-agonist results in bronchodilation of large airways as well.
Central airway obstruction. Because of the frequency-dependent distribution of
oscillatory pressures within the airway tree, FOT provides separate, although not entirely
independent, indices of large and small airway responses. Thus, changes of resistance in
the larger airways are manifest by FOT as uniform changes in Rrs at all oscillation
frequencies, both low and high. An increase in resistance of the large airways was reported
in a recent study of rescue workers at the World Trade Center site in New York [18].
Rescue workers with no history of cigarette smoking exposed to large-particle air
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OSCILLOMETRY: FOT AND IOS
pollution at the World Trade Center site manifested, at baseline, uniformly increased Rrs
at all oscillatory frequencies studied between 5–35 Hz, as shown in figure 8, pre- and postnebulised b-agonist.
Ironworkers with a history of cigarette smoking showed greater baseline increases in
low-frequency Rrs5, and, accordingly, a frequency dependence of resistance that is
characteristic of peripheral airway obstruction [7, 18, 29, 36, 82, 116, 117]. Responses to
nebulised b-agonist showed uniform decreases in Rrs across all frequencies in
nonsmokers, while smokers manifested larger decreases in Rrs5 than in Rrs20 [18].
Nonresistive components of forced oscillation technique. A second discriminant
between mono- and multifrequency FOT concerns reactive components of applied
pressure oscillations, reactance Xrs(f)-tracings, which appear prominently in
multifrequency FOT. Reactance can be assessed by computer-assisted analyses
utilising FFT; however, monofrequency FOT has not been widely adapted to
conveniently calculate Xrs.
Just as with the interpretation of Rrs, oscillation frequency provides a means of
examining different regions of the airway tree using Xrs (vide infra): at low oscillation
frequencies, elastic elements in peripheral airways are the dominant reactant to applied
pressure, and reflect small airway mechanical properties. In airflow obstruction, small
airways are functionally obstructed, due to peripheral airway inflammation in both
asthma and COPD. This results in portions of the distal lung periphery that are "in the
shadow" of effective obstruction of small airways. This pathological process leads to an
increase in the magnitude of Xrs at low frequencies. At high frequencies, accelerative
forces are the predominant reactant to applied pressures and occur virtually exclusively
in large airways where they are related to inertial properties. It should be noted that Van
Noord et al. [78] reported qualitatively similar changes in Xrs(f) tracings in patients with
diffuse interstitial lung disease and obstructive lung disease. Accordingly, changes in lowfrequency Xrs are not specific to obstructive lung disease, but rather reflect peripheral
airway disease. Mechanical interpretations of changes in low-frequency Xrs in obstructive
and restrictive lung disease are considered in detail in the methodology section.
Resistance Rrs kPa·s·L-1
1.0
0.8
0.6
0.4
0.2
0.0
0
5
10
20
15
Frequency ƒ Hz
25
30
35
Fig. 8. – Respiratory resistance (Rrs(f)), plotted as a function of oscillatory frequency pre- (––) and post (----)
-bronchodilator in an ironworker exposed to large-particle air pollution at the World Trade Center site. Note
increased Rrs at all frequencies, with no significant frequency dependence of resistance at baseline. After
nebulised b-agonist, Rrs(f) decreases in a parallel manner relative to baseline pre-bronchodilator.
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H.J. SMITH ET AL.
Figure 9 illustrates IOS Xrs(f) tracings in the asthmatic child whose Rrs(f) tracings preand post-nebulised b-agonist are shown in figure 6. Figure 9 shows that after b-agonist,
Xrs at 5 Hz (Xrs5) changes from -0.31 to -0.26 kPa?s?L-1 and the frequency at which Xrs is
zero (resonant frequency = fres, vide infra) changes from 18 to 17 Hz (6%). More
strikingly, the overall curvature of the Xrs(f) tracing changes from concave to the zero-X
axis to being convex to the zero-X axis. This change in curvature is consistent with Xrs(f)
tracings described by Clement et al. [36], who reported that patients with airflow
obstruction manifested a loss of the downward concavity of Xrs(f) tracings that is
commonly seen in normal subjects. b-agonist produced only small changes in Xrs5 and
fres in figure 9; however, the change in the overall Xrs(f) tracing curvature at frequencies
below fres was dramatic.
Previous investigations have emphasised that low-frequency Xrs and Rrs are most
sensitive to changes in peripheral airway function, and Xrs5 has been used as a primary
efficacy variable [113–115, 122, 123]. However, in small children, respiratory frequency is
commonlyw20–30 breaths?min-1, and, accordingly, the higher harmonics of fundamental
respiratory frequency may encroach on the lowest FOT frequencies analysed [41, 68]. As
a result, Xrs5 manifests relatively greater measurement noise. Some IOS studies in
children have reported failure of Xrs5 to manifest significant changes after inhaled
corticosteroids or b-agonists [42, 115, 124]. Marotta et al. [42] showed that the Xrs10
response to b-agonist, but not the Xrs5 response, manifested a significant difference
between asthmatic and nonasthmatic atopic children. This was associated with less
variability in Xrs10 responses compared with Xrs5.
The absolute value of Xrs (|Xrs|) changes differently as a function of oscillation
frequency below and above fres. At low frequencies of oscillation, below fres, |Xrs|
decreases as oscillation frequency increases up to fres. At fres, |Xrs| is zero. As oscillation
frequency increases above fres, |Xrs| increases with further increases in oscillation
frequency.
Because of this difference in the relationship between magnitude of Xrs and oscillation
frequency below and above fres, a quantitative index of Xrs magnitude at frequencies
below fres was developed by integrating all negative values of Xrs [18, 45, 52]. This index,
0.5
Reactance Xrs kPa·s·L-1
0.4
0.3
0.2
0.1
AX post
0
-0.1
-0.2
-0.3
AX pre
-0.4
-0.5
0
5
10
15
20
Frequency ƒ Hz
25
30
35
Fig. 9. – Respiratory reactance (Xrs(f)), plotted as a function of oscillatory frequency pre- (––) and post- (----)
bronchodilator. Same subject as figure 6. The integrated low-frequency reactance area (AX), is shown by vertical
hatching pre-bronchodilator, and by diagonal hatching post-bronchodilator. This area is reduced by y50% from
pre- to post-bronchodilator, associated with marked change in curvature of the Xrs(f) tracing. In comparison,
there are small changes in Xrs at 5 Hz and resonant frequency from pre- to post-bronchodilator.
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OSCILLOMETRY: FOT AND IOS
designated AX, provides an integrative function to include changes in the magnitude of
low-frequency Xrs, changes in fres and changes in curvature of the Xrs(f) tracing. AX
includes Xrs magnitudes at 5 Hz and slightly higher oscillation frequencies which
manifest improved signal-to-noise ratio, as noted above for atopic asthmatic children
[42]. It is represented graphically in figure 9 as the area under the zero Xrs axis above the
Xrs(f) tracing. As discussed below, this integrative index provides a single quantity that
reflects changes in the degree of peripheral airway obstruction and correlates closely with
frequency dependence of resistance. In figure 9, AX decreases by 50% after b-agonist,
closely comparable to the decrease in frequency dependence of resistance measured
between 5 and 15 Hz in the same child shown in figure 6, when R5-R15 decreased from
0.36 kPa?s?L-1 to 0.16 kPa?s?L-1 after b-agonist.
The perspective presented here of AX in relation to peripheral airway function, results
directly from the details presented in the methodology section, namely that lowfrequency Xrs essentially expresses the ability of the respiratory tract to store capacitive
energy, which is primarily resident in the lung periphery. In contrast, at frequencies
above fres, I, which is primarily resident in proximal conducting airways, contributes
significantly to the dissipation of externally applied pressures [6, 46]. Thus, oscillation
frequencies above fres reflect mechanical properties of more proximal conducting
airways. Because of these differences in mechanical properties reflected by low- and highfrequency oscillation, calculation of the arithmetic mean Xrs is not likely to be optimally
useful to assess pulmonary mechanical responses. Thus, Van Noord et al. [29] reported
that the mean value of Xrs change was less sensitive than FEV1 in assessing the effect of
histamine. However, their graphic mean Xrs–frequency data reveal changes in the
estimate of AX from y0.15 at baseline, to 1.7 or 2.5 kPa?L-1 when mean decrease in
specific airway conductance (sGaw) was 40% or 15% in FEV1. These increases in AX of
1,000–1,500% are comparable to those measured using IOS in the current author’s
laboratory during methacholine challenge: the patient shown in figure 6 manifested an
increase in AX from 0.34 at baseline to 7.5 kPa?L-1 (w2,000% increase) after cumulative
exposure to methacholine up to 1.0 mg?mL-1. Furthermore, the study of Van Noord
et al. [77] during assessment of reversibility of airflow obstruction by FOT, body
plethysmography and spirometry reported that changes in mean Xrs did not contribute
significantly to discriminant function beyond spirometry, Raw and Rrs at 6 Hz. In
contrast, estimated AX, approximated from their graphic mean Xrs–frequency data,
showed a 50% reduction after salbutamol, from y3.1 to 1.5 kPa?L-1. Both the baseline
AX in patients with airflow obstruction and the AX decreases in response to b-agonist are
comparable to those recently reported using IOS [101].
The empirical observations discussed above do not prove that any particular
engineering model is a true representation of the lung, especially the diseased lung as
emphasised by Van Noord et al. [78]. Nevertheless, FOT results predicted by models
may correlate usefully with independent clinical physiological and pathophysiological
evidence. Quite apart from engineering models, an intuitive understanding of Xrs may be
appreciated from the physical principles elucidated above and amplified in the foregoing
discussion of methodology. The applicability of high frequencies to large central airways
and low frequencies to peripheral airways is not a consequence of any particular
engineering model, but is observed empirically both in Rrs and Xrs.
Clinical interpretation of forced oscillation technique
As also noted in the methodology discussion of FOT, abnormalities of Xrs are not
specific to obstructive lung disease, because these same patterns have been reported in
lung fibrosis [78]. In clinical diagnostic lung function testing including FOT, spirometry,
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H.J. SMITH ET AL.
gas diffusion and body plethysmography, the problem is not usually distinguishing
between obstructive and restrictive disease. The more important issue is the relative
severity of pathophysiological abnormality. Furthermore, there is evidence to suggest
that the early pathological lesion in lung fibrosis is inflammation of the small airways
[125]. Thus, changes in Xrs magnitude in lung fibrosis and in peripheral airflow
obstruction may both reflect peripheral airway inflammation. If these nonspecific Xrs
abnormalities in lung fibrosis represent small airway inflammation, they may respond to
anti-inflammatory treatment, analogous to the way asthmatic peripheral airway
inflammation responds to corticosteroids. Such responses are more likely to be found
in FOT parameters than in spirometry. Clinical interpretation may then be considered in
the setting of response to treatment interventions.
Clinical interpretation of FOT can be related both to effects of airway smooth muscle
tone and airway inflammation. Below, effects of anticholinergic, b-agonist or
corticosteroid medications are represented, because these agents are most commonly
utilised clinically. Commonly observed changes in FOT measures in patients with
obstructive lung disease are illustrated. Rrs is considered first.
Rrs effects. While inflammation is a cellular process, it has mechanical consequences.
These consequences may be considered in relation to bronchoconstriction, defined as
increased tone of airway smooth muscles, and the common perception of bronchodilation
defined as a decrease in smooth muscle tone.
When airway smooth muscle tone increases, Rrs increases because of decreased airway
lumen. Airway lumen is also decreased with inflammation or oedema in the walls of the
airways. Therefore, Rrs increases as a result of inflammation and oedema. Peripheral
airways have much smaller lumina than central (large) airways, and inflammation/
oedema in the walls of peripheral airways can reasonably be expected to have a
proportionately larger effect on lumen size than inflammation/oedema in larger airways.
In the discussion that follows, "low-frequency Rrs" will be denoted as Rrs at frequencies
v15 Hz and "high-frequency Rrs" as Rrs at frequencies w20 Hz, with the latter term
synonymous with large airway resistance.
If an intervention, such as inhaled anticholinergic, achieves bronchodilation with no
effect on inflammation, it may be expected that large airway lumen will increase, with
little effect on peripheral airway lumen. In this event, large airway Rrs will decrease. Lowfrequency Rrs will decrease to a similar degree and little or no change in frequency
dependence occurs. This is illustrated in a 55-yr-old patient with COPD in figure 10.
If an intervention such as inhaled b-agonist achieves bronchodilation with little or no
effect on inflammation, it may be expected that peripheral airway lumina will increase, in
addition to any release of bronchoconstriction in large airways. In this case, lowfrequency Rrs will decrease out of proportion to high-frequency Rrs.
In asthmatic patients, both high-frequency and low-frequency Rrs may decrease, with
relatively greater decrease in low-frequency Rrs and associated decrease in frequency
dependence of resistance as illustrated in figure 6.
In patients with COPD, a decrease in low-frequency Rrs after b-agonist with little or
no change in high-frequency Rrs is commonly observed, as illustrated in figure 7. In COPD
patients with lung hyperinflation, little or no decrease in Rrs may occur after
b-agonist inhalation, particularly if there is an associated fall in resting end-expiratory
lung volume. If Rrs remains the same after b-agonist while end-expiratory lung volume
decreases, this represents "functional bronchodilation", because the same resistance
pertains at lower operating lung volumes. Accordingly, failure of Rrs to decrease in patients
with COPD need not be considered as "no response" to b-agonist bronchodilator.
If an intervention such as inhaled corticosteroids achieves a decrease in inflammation
94
OSCILLOMETRY: FOT AND IOS
Resistance Rrs kPa·s·L-1
2.0
1.6
1.2
0.8
0.4
0.0
0
5
10
20
15
Frequency ƒ Hz
25
30
35
Fig. 10. – Respiratory resistance (Rrs), plotted as a function of oscillation frequency in a 55-yr-old male with
chronic obstructive pulmonary disease pre- (––) and post- (----) anticholinergic bronchodilator. Note that Rrs at
5 Hz is markedly elevated with marked frequency dependence of Rrs. After inhaled anticholinergic bronchodilator, there is a significant decrease in Rrs that is nearly identical at all frequencies, indicating a decrease in
proximal airway resistance, with little or no effect on peripheral airways
with no effect on airway smooth muscle tone, FOT responses might be expected to reflect
a relatively greater impact due to decrease in peripheral airway inflammation with
resultant increase in peripheral airway lumina. Such an effect results in a significant
"dilation" of peripheral airways due to decreased inflammatory encroachment on
peripheral airway lumina. Thus, a decrease in peripheral airway resistance can be
expected, manifest as a greater decrease in low-frequency than in high-frequency Rrs, and
concomitant decrease in frequency dependence.
In asthmatic patients, a decrease in large airway Rrs (high-frequency Rrs) may also
occur. In patients with COPD, there may be a decrease in low-frequency Rrs; however,
little or no decrease in Rrs may be manifest, especially if lung hyperinflation is present.
Xrs effects. How then does decreased inflammation manifest itself in patients with
COPD? As noted in the preceding section, describing nonresistive components of FOT,
the magnitude of low-frequency Xrs is increased in COPD due to functional peripheral
airway obstruction, with resultant contraction of surface area of the lung periphery
exposed to low-frequency oscillations. Indeed, low-frequency Xrs is more sensitive to
peripheral airway obstruction in COPD/emphysema than Rrs. In the presence of
peripheral airway obstruction in patients with COPD, relatively small increments to
airways resistance may occur because of the large cumulative cross-sectional diameter of
all airways in the lower generations of airways, as manifest in the trumpet model of
Weibel [126]. Accordingly, body plethysmographic measurement of airway resistance
may be nearly normal, and only by measuring absolute thoracic gas volume is the
abnormality manifest.
If peripheral airway inflammation is decreased by administration of inhaled
corticosteroids, peripheral airway lumina increase and the patency of small airways
expands in the direction of the lung periphery. As a result, a portion of the lung periphery
comes "out of the shadow" of small airway obstruction and a larger surface area is
presented to the low-frequency oscillations. This acts to decrease the magnitude of lowfrequency Xrs. This is illustrated in figure 11a showing IOS tracings in a COPD patient at
95
H.J. SMITH ET AL.
a) 0.5
Reactance Xrs kPa·s·L-1
0.4
0.3
0.2
0.1
AX post
0.0
-0.1
-0.2
-0.3
AX pre
-0.4
-0.5
Resistance Rrs kPa·s·L-1
b)
1.0
0.8
0.6
0.4
0.2
0.0
0
5
10
15
20
Frequency ƒ Hz
25
30
35
Fig. 11. – a) Respiratory reactance (Xrs), plotted as a function of oscillatory frequency in a 73-yr-old male with
chronic obstructive pulmonary disease before and after 4 weeks inhaled corticosteroid (ICS) therapy. ––: preICS; ----: post-ICS. Integrated low-frequency reactance area (AX) is vertically hatched pre-ICS and diagonally
hatched post-ICS. AX is decreased by y50% after 4 weeks of therapy, resonant frequency by 10% and Xrs at
5 Hz decreased by 0.12 kPa?s?L-1. b) Respiratory resistance (Rrs) plotted as a function of oscillation frequency in
the same patient. ––: pre-ICS; ----: post-ICS. Note that Rrs at 20–22 Hz is relatively unchanged, while Rrs at 5
and 10 Hz are substantially decreased. High-frequency resistance (Rrs at 25–35 Hz) is decreased after ICS
therapy. See text for discussion.
baseline (–––) and after 4 weeks of inhaled corticosteroids treatment (-----). AX decreased
from 3.0 to 1.3 kPa?L-1 after inhaled corticosteroid treatment. In this patient, Rrs and
frequency dependence of the Rrs(f) tracing show significant decreases, as illustrated in
figure 11b; Rrs5 improved from 0.68 to 0.48 kPa?s?L-1, Rrs15 from 0.41 to 0.35 kPa?s?L-1.
Furthermore, this patient with COPD manifests somewhat "responding" large airways,
as his high-frequency Rrs (at 30–35 Hz) also decreased by y20%.
Figure 12 shows tracings in a COPD patient when stable at baseline and during the
onset of an exacerbation. Figure 12a shows baseline reactance area AX = 1.2 kPa?L-1,
with increases to 1.6, 2.4 and 4.3 kPa?L-1 over a duration of 9 days of exacerbation. Rrs5
increased significantly, but less dramatically from 0.51 at baseline to 0.54, 0.59 and
0.65 kPa?s?L-1 during exacerbation, shown in figure 12b. Frequency dependence,
calculated as the fall in Rrs from 5 to 15 Hz, was 0.15 kPa?s?L-1 when stable at baseline,
and increased to 0.2, 0.23 and 0.31 kPa?s?L-1 during exacerbation.
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OSCILLOMETRY: FOT AND IOS
a) 0.5
Reactance Xrs kPa·s·L-1
0.4
0.3
0.2
0.1
0.0
-0.1
-0.2
-0.3
-0.4
-0.5
Resistance Rrs kPa·s·L-1
b)
1.0
0.8
0.6
0.4
0.2
0.0
0
5
10
15
20
Frequency ƒ Hz
25
30
35
Fig. 12. – a) Respiratory reactance (Xrs(f)) in a 73-yr-old male chronic obstructive pulmonary disease patient
when stable at baseline and during onset of exacerbation over a duration of 9 days. Note progressive increase in
the reactance area (AX) from trial 1 to trial 4. b) Respiratory resistance (Rrs(f)) in the same patient. Note
progressive increase in Rrs at 5 Hz (Rrs5) from trial 1 to trial 4. Changes in Rrs5 were relatively smaller than
changes in AX over a duration of 8 days. –––: trial 1, baseline; -----: trial 2, 7 days after trial 1; –– - ––: trial 3,
8 days after trial 1; –– -- ––: trial 4, 9 days after trial 1.
The close correlation between changes in AX and changes in frequency dependence of
resistance in individual patients shown in figures 6–12 are confirmed across individuals in
the occupational study reported by Skloot et al. [18], who found a correlation of 0.92
between frequency dependence of resistance and AX across a sample of ironworkers at
the World Trade Center site, with variable exposure to cigarette smoking and largeparticle air pollution, and resultant variability in both large and small airway
obstruction. The close correlation between frequency dependence of resistance and
AX is consistent with both indices reflecting small airway function.
Coherence. Coherence, first introduced by Michaelson et al. [5], is defined as the autoand cross-correlations of phase and amplitude of oscillatory pressure and flow
components. It reflects, in an "engineering sense", the linearity of the respiratory
system and, in a "biological sense", the variability of the respiratory system from time to
time within the sample of data. Marked temporal variability of the respiratory system
within a breath occurs commonly in COPD, where even during quiet breathing, dynamic
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H.J. SMITH ET AL.
compression of intrathoracic airways may occur. As a result, Rrs and Xrs may increase
substantially during expiration.
Figure 13a illustrates a patient with severe COPD, with volume and Zrs5 as functions
of time. Figure 13b shows coherence plotted as a function of oscillation frequency, with
separate tracings for average combined inspiration/expiration as well as for inspirationonly and expiration-only.
Figure 13a shows marked changes in Zrs5 with respiratory phase, similar to those
shown by Marchal and Loos [68]. There is a clear decrease in Zrs5 at the onset of
inspiration, keeping minimal values until end-inspiration. A marked abrupt rise in Zrs5
occurs at the onset of expiration with elevated values including end-expiration. In figure
13b, the value of averaged coherence at 5 Hz, 0.4, is distinctly lower than at frequencies
i10 Hz.
Volume L
a) 1.5
1.0
0.5
0.0
Zrs5 kPa·s·L-1
-0.5
3
2
1
0
0
10
20
Time s
30
40
b) 1.0
0.9
Coherence g2
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
5
10
15
20
Frequency ƒ Hz
25
30
35
Fig. 13. – a) Volume and magnitude of respiratory impedance at 5 Hz (Zrs5) plotted as a function of time
during a 40-s impulse oscillometry system (IOS) test in a 53-yr-old patient with severe chronic obstructive
pulmonary disease. Note marked increase in Zrs5 during the expiratory phase of every tidal volume. b)
Coherence of all IOS data (global average (–––) and separated inspiratory (–– - ––) and expiratory (-----)
respiratory phases) plotted as a function of oscillation frequency during the 40-s test. Note low coherence for
average data (v0.5) at 5 Hz with prominent increase to 0.7 at 10 Hz. See text for discussion.
98
OSCILLOMETRY: FOT AND IOS
Numerical calculations of coherence during the separate respiratory phases reveal that
inspiratory-only and expiratory-only coherences are systematically greater than the
combined coherence over the entire spectrum of oscillatory frequencies. The tracings in
figure 13 are consistent with more uniformity of respiratory mechanics within the
separate inspiratory and expiratory phases than for the combined total breath average.
At 10 Hz, the coherence averaged across both respiratory phases is 0.7, while that for
separate inspiratory and expiratory data are both 0.9, reflecting differences in respiratory
mechanical parameters that pertain to the separate respiratory phases. Despite the very
low coherence for combined inspiration/expiration, three consecutive 40-s impulse
oscillometry system recordings obtained within 5 min manifested an average respiratory
resistance at 5 Hz of 1.08, 1.0 and 1.02 kPa?s?L-1 and reactance area of 5.9, 6.1 and
6.2 kPa?L-1. Thus, the within-phase uniformity of mechanical parameters reflected by
separate inspiratory and expiratory coherences is borne out by standard deviations of
v5% for triplicate measures.
Summary
The aim of this chapter has been to describe the unique and clinically relevant
information that forced oscillation technique (FOT) provides. This may be derived
without mathematical mastery of technological principles of the equipment and/or of
numerical models. It is emphasised that recognition of the change in respiratory
mechanical parameters as a function of oscillation frequency is necessary to appreciate
the outstanding value of FOT in its ability to assess peripheral airway function. This
has been one of the major challenges in respiratory diagnostics up to the present time.
The short duration of the FOT test, 20–30 s, makes it particularly useful as part of a
diagnostic programme of lung function testing; it is not suggested that FOT be used in
lieu of conventional pulmonary function testing, but rather in addition. FOT measures
resting breathing while spirometry assesses maximal respiratory performance of the
patient. The special value of FOT in terms of short-term response to bronchial and
therapeutic challenge has been emphasised as well as its value in monitoring long-term
trend responses to therapy.
The simplicity of FOT measurements and its minimal requirements on subject
cooperation are in rather sharp contrast to its current limited clinical acceptance. Two
primary reasons for the present limited application of FOT include the need for
viewing respiratory mechanical parameters over a range of frequencies and the
resultant central-peripheral specificity of oscillatory parameters, with specific
emphasis on the reflection of peripheral airway function by low-frequency reactance.
Indeed, lack of awareness of this ability of FOT to assess peripheral airway function
has turned physicians to the use of multiple replicates of high-resolution computed
tomography lung scans to assess small airway function. Other reasons for limited use
of FOT currently may include the greater variability of FOT measures compared with
spirometry. Despite such variability, use of at least three replicate FOT measures
combined with therapeutic challenge can provide sensitive evaluation of small airway
function.
The freedom allowed to the subject to breathe "naturally" imposes increased demands
for vigilance on the operator, who must maintain a quiet environment for forced
oscillation technique testing. Operators must also reassure subjects that their
relaxation is needed, except for the facial musculature ensuring tight lip closure on
the mouthpiece. Posture must be supported to maintain subject comfort and the
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H.J. SMITH ET AL.
instrument mouthpiece must be brought to the subject to avoid stretching of the neck.
Finally, the availability of results from a brief test must not lead the operator to accept
a single measurement, but rather, the usual clinical testing procedure of at least three
replicate measures is required.
Keywords: Forced oscillation technique, impulse oscillation technique, reactance,
resistance, respiratory impedance.
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