Vol. 91, Issue 6, 2767-2775, December 2001
INNOVATIVE TECHNIQUES
Flowmetric comparison of respiratory inductance
plethysmography and pneumotachography in horses
Andrew
Hoffman1,
Heike
Kuehn1,
Klaus
Riedelberger2,
Rachel
Kupcinskas1, and
Mary Beth
Miskovic1
1 Department of Clinical Sciences, Tufts University School
of Veterinary Medicine, North Grafton, Massachusetts 01536; and
2 Internal Medicine Clinic, Veterinary University, 1210 Vienna,
Austria
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ABSTRACT |
Respiratory inductance
plethysmographic (RIP) and pneumotachographic (Pn) flows were compared
dynamically in horses with bronchoconstriction. On a
breath-by-breath basis, RIP was normalized to inspiratory volume from
Pn, and peak [peak of subtracted final exhalation waveform
(SFEmax)] and selected area [integral of subtracted final waveform during first 25% of exhaled volume (SFEint)]
differences between RIP and Pn flows during early expiration were
measured in three settings: 1) healthy horses
(n = 8) undergoing histamine bronchoprovocation;
2) horses with naturally occurring lower airway obstruction
(AO) (n = 7); and 3) healthy horses
(n = 6) given lobeline · HCl to induce
hyperpnea. In setting 1, histamine challenge induced a
dose-dependent increase in SFEmax and SFEint
differences. A test index of airway reactivity (interpolated histamine
dose that increased SFEmax by 35%) closely correlated
(rs = 0.93, P = 0.001) with
a conventional index (histamine dose that induced a 35% decrease in
dynamic compliance). In setting 2, in horses with AO,
SFEmax and SFEint were markedly elevated, and
their absolute values correlated significantly (P < 0.005) with pulmonary resistance and the maximum change in
transpulmonary pressure. The effects of bronchodilator treatment on the
SFEmax and SFEint were also highly significant
(P < 0.0001). In setting 3, hyperpnea, but not tachypnea, caused significant (P < 0.01) increases
in SFEmax but not in SFEint. In conclusion,
dynamic comparisons between RIP and Pn provide a defensible method for
quantifying AO during tidal breathing, without the need for invasive instrumentation.
noninvasive; dynamic; resistance; gas compression; heaves
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INTRODUCTION |
INFLAMMATORY AIRWAY
DISEASES and more severe recurrent airway obstructions are common
clinical problems encountered in veterinary medicine (27,
32). Clinical examination is limited in sensitivity (28); therefore, more objective tests have been sought to
improve early detection of these exercise-limiting problems. In
contrast to human medical practice, in which lung function tests are
employed routinely, the complexity, invasiveness, and limited
sensitivity of conventional lung function tests performed during tidal
breathing have hampered more widespread use of these in animals. Recent progress in the development of lung mechanical function tests, however,
has been made on two fronts: 1) the application of a forced
expiratory maneuver (6) or 2) forced
oscillatory mechanics, which provide information concerning frequency
dependence of resistance (22, 23). Both methods have been
employed during histamine challenge, providing further information on
airway reactivity and improving sensitivity to detect airway
obstruction at a very early stage (6, 12, 13). These more
sensitive diagnostic tests have facilitated earlier interventions,
which theoretically should reduce or prevent the decline in lung
function that can be seen in older horses. Unfortunately, even these
newer tests, which are more sensitive, have not been adapted for field
application and require significant energy supplies. Evaluation of lung
function in the animal's natural setting would empower the
veterinarian to detect problems early in their course, encourage serial
examinations, and permit study of risk factors for these highly
prevalent obstructive lung diseases.
Previously, our laboratory considered the use of respiratory inductance
plethysmography (RIP) for field application (23), because
previous work suggested that relative changes in phase angle (i.e.,
thoracoabdominal asynchrony) derived from RIP could be employed as a
measure of airway obstructions in humans (1, 10, 29). In
contrast to these earlier studies, our laboratory found in horses that,
despite remarkable changes in breathing pattern and phase shifts in rib
vs. abdominal displacement, the severity of both phase-shift and airway
obstruction did not correlate sufficiently for diagnostic use
(23). This was also evident in earlier studies in humans
with chronic obstructive pulmonary disease (29).
Furthermore, RIP, being a plethysmographic measurement, is prone to
errors in the measurement of volume or flow, because of gas compression
or rarefaction during obstructions (15, 17, 21).
That volume displacement at the airway opening and thorax differ during
obstruction served as a basis for unique indexes of airway obstruction
in animals measured from double-chamber plethysmography (8, 18,
26, 31). This concept was also applied to the development of
barometric whole body (single-chamber) plethysmography (3-5,
9, 11).
In this paper, we explore an analogous technology for use in large
animals. For practical reasons, we chose boxless plethysmography for
large animals (RIP) and compared the flow-derived indexes from RIP
(volume, flow) with flow-derived measurements at the airway opening,
which were measured using pneumotachography. Although there are clear
differences between RIP and body plethysmography, we hypothesized that
compression and rarefaction of gas due to airway obstruction would
create similar phase and magnitude shifts that could be quantified.
A comparison between RIP and nasal flow was made in three settings:
1) histamine bronchoprovocation, 2) severe lower
airway obstruction before and after bronchodilation, and 3)
during experimentally induced hyperpnea in nonobstructed horses.
Settings 1 and 2 were used to test the hypothesis
that this new method of measurement gives similar results to
conventional mechanics, and setting 3 was employed to
examine the effects of increased respiratory frequency or flows in
nonobstructed horses, as would occur during stress, excitement, and
exercise (i.e., situations that might confound the measurements of
airway obstruction).
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MATERIALS AND METHODS |
All procedures described were approved by the Institutional
Animal Care and Use Committee at Tufts University.
Details of the bench-top models of the test device.
The frequency response of the flow derived from RIP
(
dSum) and that of flow derived from
pneumotachograph (pn) signals were compared using a
step test and an oscillatory model. For the step test, one inflated
balloon (20-liter internal volume) was attached to one side of the
pneumotachograph; the other side was closed with a rubber seal. The
11th intercostal space (Rib) and 18th rib [abdominal (Abd)] sensors
were secured around the balloon. To perform the test, the rubber seal
was pierced, and the time delay between dSum and
pn to reach a flow of 40 l/s (i.e., higher than the
maximal flow encountered in our study) was measured for three runs. The
average time delay was 12 ms. A second system was employed to examine
potential phase differences between pn and
dSum during oscillation. This system employed a
two-element (resistance and elastance) series model of the horse's respiratory system. The resistance element was a 0.4-m noncompliant length of polyvinyl chloride (7.2-cm ID) attached to an elastic element, a large animal anesthesia bag (30 liters). The
pneumotachograph was positioned at the proximal end of the tubing, and
the inductance bands were wrapped in parallel around the spherical
anesthesia bag, located at the distal end of the model. The model was
oscillated (0.25-4.0 Hz) using constant end-expiratory pressure
(2-5 cmH2O), with either a mechanical ventilator (Bear
1, model BV-512, Bourns Medical Systems, Riverside, CA), or forced
oscillatory mechanics delivery system (On the Nose, Scientific
Solutions, Eden Mills, Ontario).
Calibration, signal acquisition, and signal processing.
The pneumotachograph (Fleisch no. 5, OEM Medical, Lenoir, NC) was
calibrated using a precision syringe (3-liter volume syringe, Hans
Rudolph, Kansas City, MO). The pneumotachograph was connected via
tubing to a differential pressure transducer (DP45-14, Validyne Engineering) and carrier demodulator amplifier. An esophageal balloon
catheter was placed to the level of the midthorax and connected to a
differential pressure transducer (DP45-28, Validyne Engineering)
and amplified. The opposite pole of the pressure transducer was
connected to a side port in the gas-collection mask to obtain
transpulmonary pressure measurements.
For calibration of RIP, an oscillator (large-animal oscillator,
Ambulatory Monitoring, Sawmill, NY) was used, the signal from which was
demodulated downstream using standard diagnostic hardware (Respitrace
Interface, Ambulatory Monitoring, Saw Mill, NY). The sensitivity of the
two RIP sensors (Rib and Abd bands) was made equal by adjusting their
analog gain settings while stretching them dynamically (0.25-0.5
Hz) off the horse to identical lengths. This required a system of
hangers, and their equivalence was later confirmed by placing them as
close as possible to each other on a horse.
The Rib and Abd volume signals were summed to obtain a third analog
volume signal, Sum (RIP interface, Ambulatory Monitoring). The three
analog signals that were derived from these sensors (Sum, Rib, and Abd)
were digitized (30 Hz; ADAPC, Buxco Electronics, Sharon, CT),
displayed, and recorded on a personal computer by using
data-acquisition software (XA BioSystem, Buxco Electronics). We
differentiated the Sum signal to obtain Sum flow
(dSum) and applied smoothing (50 ms) to
dSum and pn equally.
The waveforms (dSum and pn)
acquired in horses in each of parts I-III were analyzed
post hoc using commercial software (AcqKnowledge, BIOPAC Systems). The
RIP volume signal (dSum) was calibrated to the
inspired volume recorded from the pneumotachograph by adjusting the
gain setting of dSum (volume) signal post hoc to
correct for the difference in their amplitudes by using a
multiplicative constant. The rationale to calibrate the Sum signal to
pn during inspiration was to normalize the signal to
correct tidal volume (VT) while tracking the dynamic events
that represent compression or rarefaction. This permitted within- and
between-subject comparisons. After calibration of the Sum signal, this
signal was differentiated to obtain dSum. Next, the
two flow waveforms (i.e., dSum 
pn flow) were digitally subtracted to obtain a third
waveform that represented the dynamic differences between these flows, which was subsequently analyzed. The following variables were derived
from the final subtracted waveform (see Fig. 2): 1) peak of
the subtracted waveform during exhalation (SFEmax) and
during inhalation (SFImax); and 2) the integral
of the subtracted waveform during the first 25% of exhaled volume
(SFEint) and first 25% of inspired volume
(SFIint). For calculation of these indexes, the beginning
of inspiration and expiration was defined by the upward and downward
directed zero crossings of the dSum signals, respectively.
Part I: Comparison of test system with conventional methods for
measuring airway responses to histamine (airway reactivity).
Eight standardbred mares, with no clinical, lung radiographic, or
airway endoscopic abnormalities, were included in part I. These horses were subjected to histamine bronchoprovocation as previously described (7, 22). Horses were sedated with
xylazine (0.75 mg/kg body wt), and their heads were maintained in a
horizontal position during measurements (22). Respitrace
(Ambulatory Monitoring, Saw Mill, NY) bands (4 cm wide) were placed on
the horses: one at the 11th intercostal space (Rib), and the other
placed directly behind the last (18th) rib (Abd). None of the horses
employed for study were conditioned to the placement of inductance
bands. First, baseline lung mechanisms, including pulmonary resistance (RL), dynamic compliance (Cdyn), maximum change in
transpulmonary pressure (
Ptpmax), breathing rate (f),
and VT, were recorded, in addition to the test variables
(SFEmax, SFImax, SFEint,
SFIint). Next, increasing concentrations of histamine
diphosphate in saline aerosol (saline plus 1, 2, 4, 8, 16, and up to 32 mg/dl histamine diphosphate; Sigma Chemical) were administered for 2 min each, through a nebulizer (Pari LC Plus, Pari Respiratory
Equipment, Monterey, CA) powered by a high-flow (10 l/min) compressor
(ProNeb Turbo, Pari Respiratory Equipment). The test was terminated
when the Cdyn for the horse dropped to <50% of the baseline,
respiratory rate doubled, or a horse was visibly dyspneic or coughing.
A dose-response curve was generated for Cdyn and for each test
variable. To compare the measurements of airway reactivity using a test
with conventional measurements, we compared the log of the provocative
concentration that induced a 35% decrease in Cdyn, as is standard in
the horse, with the log of the histamine concentration associated with
a 35% increase in SFEmax or SFEint. These
indexes were compared using Spearman's correlation coefficient.
Part II: Changes observed in the test and
conventional method during bronchodilation.
Seven horses that presented to Tufts University School of Veterinary
Medicine with spontaneous recurrent airway obstruction ("heaves")
were employed for part II. These horses exhibited severe clinical signs of lower airway obstruction, with baseline
Ptpmax >30 cmH2O. First, a baseline
recording of classical lung mechanics (RL, Cdyn,
Ptpmax, f, VT) and test variables was made
for at least 5 min. Next, the horses were administered albuterol (450 µg; ProVentil, Schering-Plough) through a commercial drug delivery device (Equine Aeromask, Trudell Medical International, London, Ontario). This caused marked improvement in all horses. A second 5- to
10-min recording was made at least 10 min after the administration of
the bronchodilator. We analyzed the percent change in RL,
Cdyn, and Ptpmax and compared this change to the percent
change in SFEmax and SFEint. The correlations
between the test and conventional variables were made using Pearson's
correlation coefficient.
Part III: Changes observed in the test and
conventional methods during experimental hyperpnea.
Six healthy horses were administered lobeline · HCl (0.2 mg/kg
iv; Lobeline, Boehringer-Ingelheim) as a bolus over 5 s to stimulate hyperpnea. Recordings were made for 5 min during normal tidal
breathing and throughout the period of hyperpnea (30-90 s). The
reaction included a stable period of hyperpnea with high frequency and
VT (30-45 s) followed by a decline in VT
but maintenance of high frequency for several breaths. The changes in
test variables among baseline, hyperpneic, and tachypneic periods were
analyzed using ANOVA.
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RESULTS |
Bench-top models.
In the step test, the time delay between dSum and
pn to reach a flow of 40 l/s in three successive
runs was 11, 12, and 14 ms. In the oscillatory model, there was a
slight phase delay between the pn and
dSum that varied nonlinearly with frequency (Fig.
1). There was a decay in peak amplitude
of the dSum signal with frequency, with the greatest
changes appearing at frequencies of 3 and 4 Hz.
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Fig. 1.
Volumetric (A) and phase-angle (B)
comparisons between respiratory inductance plethysmography (RIP) and
pneumotachography in 2 two-element series constant-pressure, physical
models of the system of measurement. A mechanical ventilator was used
to force the system at lower frequencies (0.25-1 Hz) and an
oscillator at higher frequencies (1-4 Hz). The flow derived from
pneumotachograph (pn) signals led the flow derived
from RIP (dSum) signals in all cases, suggesting a
slightly faster frequency response for the pneumotachographic sensor.
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Part I in vivo: Effects of histamine-induced bronchoconstriction of
horses.
None of the horses reacted adversely to placement of the inductance
bands, either before or after sedation with xylazine. Histamine
aerosols altered the waveforms of dSum in relation to pn, in that the peak dSum
increased in relation to pn during the early portion
of expiration, resulting in large increases in the subtracted
(dSum pn) waveform (Fig.
2). As a result, the test variables
(SFEmax, SFImax, SFEint, and
SFIint) were altered in relation to histamine dose. Seven
out of eight horses given histamine aerosol responded with a decrease
in Cdyn and increases in RL and Ptpmax. In
horse 8, there was minimal response to histamine other than
tachypnea and coughing; therefore, this horse was not included in the
comparison between test and conventional variables. In all of the seven
remaining horses, SFEmax increased with increased histamine
dose (Fig. 3). In six of seven horses,
there was an increase in SFEint, but, in one horse with a
tachypneic response, SFEint decreased at the highest
histamine dose, after initially increasing as in the other horses.
There were highly inconsistent changes observed for SFImax
and SFIint, with increases and decreases as a result of
histamine exposure. There was a significant correlation (rs = 0.929, P < 0.001)
between the log dose of histamine that decreased Cdyn by 35% and the
log dose of histamine that increased SFEmax by 35% (Fig.
4).
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Fig. 2.
Waveforms derived from RIP and pneumotachography in a
normal horse before (A) and after (B)
administration of histamine aerosol at a dose (4 mg/ml) that evoked a
clinical response. Traces include dSum and
pn, a waveform derived from their subtraction
(dSum pn), and change in
transpulmonary pressure (Ptp).
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Fig. 3.
Histamine aerosol-induced changes in the test variable peak of
subtracted final exhalation waveform (SFEmax) vs. dynamic
compliance (Cdyn), expressed as a percentage of baseline, in
n = 7 healthy horses.
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Fig. 4.
Correlation between the provocative dose of histamine
aerosol that evoked a 35% increase in the test variable (log
PC135 SFEmax) with the dose that caused a 35%
decrease in Cdyn (log PC65 Cdyn). Values for each variable
were interpolated from their respective dose-response curves.
n, No. of horses.
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Part II in vivo: Bronchodilation of horses with
heaves.
All horses in this category presented with RL, Cdyn, and
Ptpmax values compatible with severe, recurrent airway
obstruction (22) (Fig. 5).
The administration of albuterol aerosol caused significant decreases in
RL and Ptpmax and an increase in Cdyn (Fig.
5) within 5 min. Before bronchodilation, horses with heaves showed
marked differences between dSum and
pn, particularly in the early portion of expiration.
The subtracted waveform was characterized by large, positive expiratory
spikes and smaller inspiratory spikes in the negative direction (Fig.
6). Bronchodilation reversed these
qualitative changes, accompanied by significant (P < 0.005) decreases in SFEmax and SFEint. There
were highly significant (P < 0.005) correlations
between the test variables and RL or Ptpmax
when pre- and postbronchodilator values were pooled (Fig.
7). However, there was only a trend for
the correlation between Cdyn and SFEint (r = 0.49, P = 0.054) and no significant correlation
between Cdyn with SFEmax (r = 0.38,
P = 0.14). Furthermore, there were no significant
correlations between the test variables and VT (vs.
SFEmax: r = 0.3, P = 0.25; vs. SFEint: r = 0.1, P = 0.71) or frequency (vs. SFEmax:
r = 0.26, P = 0.32; vs.
SFEint: r = 0.02, P = 0.95). Bronchodilation did not significantly alter the inspiratory test
variables SFImax or SFIint. None of the
inspiratory test variables correlated with any of the conventional
variables, with the exception that SFImax showed a trend
toward correlation with Ptpmax (r = 0.47, P = 0.067) and RL (r = 0.46, P = 0.074).
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Fig. 5.
Effect of bronchodilator [albuterol, pressurized metered
dose inhaler (pMDI), 450 µg] on conventional [Cdyn, pulmonary
resistance (RL), Ptp] and selected test
[SFEmax, integral of subtracted final waveform during
first 25% of exhaled volume (SFEint)] variables in horses
(n = 8) with naturally occurring recurrent airway
obstruction ("heaves"). Ptpmax, maximum Ptp.
Values are means ± SE.
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Fig. 6.
Waveforms derived from RIP and pneumotachography in a
horse with naturally occurring recurrent airway obstruction (heaves)
before (A) and after (B) treatment with
bronchodilator (albuterol treated: pMDI, 450 µg). Flow traces were
derived from RIP (dSum), pneumotach
(pn), or their difference
(dSum pn).
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Fig. 7.
Correlations between conventional and test variables in horses
(n = 8) with naturally occurring recurrent airway
obstruction, before ( ) and after ( )
administration of bronchodilator (albuterol, pMDI, 450 µg).
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Part III in vivo: Effect of lobeline-induced
hyperpnea.
Lobeline infusion caused marked hyperpnea followed by a period of
tachypnea in all horses (Fig. 8). The
variables SFEmax and SFImax were found to
increase significantly with hyperpnea but not tachypnea
(P < 0.001) (Fig. 9).
The dSum, pn, and subtracted (dSum pn) waveforms
showed a distinct pattern during hyperpnea. During expiration,
for instance, there was a very early positive spike, followed rapidly
by a negative deflection during much of expiration (Fig. 9). This had
the effect of increasing the absolute value of SFEmax but
decreasing the absolute value of SFEint or causing
SFEint to be a negative quantity. As a group, the area measurements SFEint and SFIint were not
significantly altered by hyperpnea or tachypnea. The variables
SFImax and SFIint were altered by hyperpnea
in the opposite direction but to the same extent as SFEmax
and SFEint. During tachypnea, when VT returned to baseline, but f remained, on average, double that at baseline, there
was no significant change in any test or conventional variable. Hence,
hyperpnea, not tachypnea, produced changes in the test variables,
specifically in the peak values (SFEmax,
SFImax).
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Fig. 8.
Representative traces from horse 4 administered
lobeline · HCl (0.2 mg/kg iv; A) to induce hyperpnea
(B) followed by tachypnea (C). Shown are the
following: dSum, pn,
dSum Vpn, and Ptp. The
x- and y-axis scales are equivalent for each
segment, as shown in A.
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Fig. 9.
Effect of lobeline · HCl (0.2 mg/kg iv) to induce
hyperpnea, followed by tachypnea in horses (n = 6).
There was a significant effect (* P < 0.005) of
hyperpnea (but not tachypnea) on SFEmax and peak of
subtracted final inhalation waveform (SFImax) but no
significant effect of hyperpnea or tachypnea on area measurements
[SFEint, integral of subtracted final wavform during first
25% of inspired volume (SFIint)].
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DISCUSSION |
Critique of the materials and methods.
One potential confounding issue was the necessity for electronic
smoothing or filtering (16). These processes introduce potential sampling and analysis errors, which may consequently attenuate the peaks and nadirs in the waveforms and/or slow the frequency response. To avoid these pitfalls, we smoothed the
pneumotachographic and RIP signals in an identical fashion before our
post hoc analyses, but potential errors may remain. Therefore, one
should view our measurements as approximations of the difference
between dSum and pn. There would
be a clear advantage to employ a band system that achieved measurements
of external flow without the need for differentiation or smoothing,
such as the piezoelectric system (25).
Frequency effects on phase and amplitude must also be considered as
sources of experimental error. The phase shift that was observed in our
positive pressure model indicated that the pneumotach sensor had a
slightly better frequency response than Respitrace. It was not possible
to increase frequency to supraphysiological levels (>1 Hz) without
overall stiffening of the bag; therefore, this may have contributed to
the phase shift because of gas compression or hysteresivity of the bag
itself. The delay in dSum caused by differences in
the frequency response of the sensors would serve only to attenuate the
phase delays (dSum vs. pn)
observed in the horses; therefore, we can assume that our test system
underestimates rarefaction and compression occurring in vivo. The decay
in dSum amplitude observed in the physical model at
higher frequencies would further amplify this error, although the
quantitative contribution of each was not determined. In contrast to
our system, Jaeger and Otis (17) did not observe phase
delays between the volumetric displacement of a piston and a spirometer
driven by that piston when there was no resistance between them. The
phase shift in the oscillatory test was qualitatively in the same
direction as the step test, supporting the concept that frequency
responses differed slightly between the pneumotachograph and RIP.
Another technical problem with our study is the use of an arbitrary
method for calibrating the RIP waveforms. We were compelled to do so,
as it was not possible to assume that a standard calibration, using
pneumotachography as a gold standard, would be valid during the various
obstructions employed in the experiment. By correcting the
dSum waveform during inspiration, we removed as much
of the differences in VT as possible. This pragmatic
approach presumably contributed to an "overcorrection," as our
animals during obstructions clearly exhibited alterations in their
inspiratory waveforms as well, and there was a trend in the correlation
between conventional and inspiratory test variables in the horses with
heaves. Despite this process of calibration, marked dynamic compressive
and rarefactive events were observed early during inspiration and
expiration in obstructed horses that caused the test variables to
change significantly. Hence, the calibration could not have altered the
test variables to the extent that the whole breath was corrected.
Phase and magnitude differences between plethysmographic and
pneumotachographic measurement of flow and volume were previously observed (17, 24). These discrepancies are a function of
resistance, lung volume, f, breathing pattern, and barometric pressure,
as previously modeled by Jaeger and Otis (17), according
to the following equation for harmonic motion: 
= tan
1 2
fRC, where R is resistance and C is
compressibility of gas. Intrapulmonary gas compression is a
normal phenomenon (14, 19, 20) during exhalation that is
accentuated by hyperpnea and exercise. Differences in plethysmographic
and pneumotachographic measures of flow, due to gas compression, worsen
in humans with asthma, chronic bronchitis, or emphysema, especially if
compounded by hyperpnea (17, 21). We employed these
concepts to generate a hypothesis that gas compression as a result,
principally of changes in resistance, would be quantifiable using our
methods. However, we did not model our system using the approach of
Jaeger and Otis (17). The equation of motion assumes
sinusoidal harmonic motion, which, in our slow, irregularly breathing
subjects, was not evident.
Despite the plethora of studies that have examined the differences
between plethysmographic and pneumotachographic volume and flow
measurements, there were no studies that we are aware of that have
dynamically compared RIP and pneumotachography (i.e., flows). Jackson
and coworkers (16) indirectly approached this problem by
comparing the kinetics of RIP and pneumotachographic flows (comparing
time to reach peak expiratory flow to total expiratory time). They
found significant differences in this variable, particularly in infants
who wheeze and older neonates with thoracoabdominal asynchrony, and
suggested caution in interpretation of uncalibrated RIP. Pennock et al.
(26) later employed piezoelectric bands coupled with
spirometry and demonstrated a qualitative difference in the magnitude
and phase between these signals in normal humans, which he attributed
to gas compression. We have taken these observations one step forward
by quantifying gas compression in our horse model using boxless plethysmography.
In our horses, there was clear evidence of gas compression by phase
delay and magnitude differences in dSum
and pn that were associated with changes in
resistance and Cdyn. As expected, the horses with severe, natural,
lower airway obstruction had markedly elevated values for conventional
and the test variables. Examination of the waveforms demonstrated that
the expiratory portion of the new test waveforms was altered to a much
greater extent than the inspiratory portion. In support, a large
discrepancy between RIP and pneumotachographic flows persisted during
airway obstruction, even after normalization. During bronchodilation, the changes in test variables during expiration were comparable to
parallel changes in Ptpmax, RL, and
Cdyn, both qualitatively and quantitatively, with a statistically
significant correlation observed between absolute values for
SFEmax or SFEint and conventional variables.
This would suggest that the system used here could be employed to
measure bronchodilator effects, again with the distinct advantage of
noninvasiveness (no need for an esophageal balloon catheter). This
would greatly facilitate serial examinations, particularly in
pharmacological studies that require daily or more frequent
measurements, and for studies involving untrained horses. Whether our
system provides more sensitive or reproducible data than a clinical
scoring technique would require further validation.
This study further demonstrates that the change in SFEmax
and SFEint during airway obstruction can be used to
generate dose-response curves and interpolate those curves to obtain
valid indexes of airway reactivity. Further studies are required to
determine the reproducibility and feasibility of this system for field
measurements. The semilog dose-response curve for the test variables
was different in shape from the conventional semilog dose-response
(i.e., histamine-Cdyn) curve, with the latter appearing more linear.
The dose-related changes in SFEmax and SFEint
resembled more what is seen in barometric whole body plethysmography,
whereby changes occur only one or two doses before the clinical
reaction (5, 9, 11). To make a comparison with
conventional methods, we chose to examine a change in the test
variables (35% increase) that matched the magnitude of change in the
conventional method (35% decrease in Cdyn) by linear interpolation.
This may not be the optimal endpoint to evaluate the airway reactivity
in horses or to analyze these curves. However, we did not want to
confound the comparison by using different methods of interpolation
between our test and conventional methods. The excellent correlation in
a small number of horses suggests that the system constructed for this
experiment could be applied to horses noninvasively to obtain similar
information on airway reactivity.
The role of changing lung volume was not revealed by this study, as we
did not measure functional residual capacity (FRC). One would expect
that histamine-induced bronchoconstriction and spontaneous lower airway
disease, such as heaves, studied here, would be associated with dynamic
hyperinflation, adding to the volume of compressed gas measured with
our system. Similar effects were observed in humans with emphysema
(17, 21). Further evidence that FRC is important to our
measurements is suggested by the work of Johanson and Pierce
(18) and later Dorsch et al. (8), who showed
that gas compression closely correlated with changes in specific airway
conductance (which accounts for changes in FRC). We speculate that
SFEmax and SFEint are also variables that are
sensitive to changes in lung volume, as a component of gas compression,
and this was supported by the effects of hyperpnea during lobeline
challenges. The use of a volumetric correction factor may be
appropriate to decrease the confounding effects of changes in lung
volume and body size on absolute values.
In part III, we attempted to answer whether hyperpnea was
associated with discrepancies in dSum and
pn. During hyperventilation in horses, this
phenomena was visualized as a transient difference between the peak
dSum and pn (SFEmax,
SFImax) at the beginning of inspiration and
expiration. The appearance differed remarkably from the
waveforms during bronchoconstriction (natural and histamine induced), where differences occurred asymmetrically, i.e.,
predominantly during expiration. Hyperpnea effects also deviated from
the effects of increased frequency alone (tachypnea) on our physical
model, whereby dSum amplitude decreased relative to
pn. Tachypnea did not have that effect in the
horses. The effect of hyperpnea, therefore, is physiological, rather
than artifactual, and may result from compression of airways during
expiration, inhomogeneities in time constants of emptying in small
airways, or increased lung volume, providing a greater compressed mass
of air. Jaeger and Otis (17) noted gas compression in some
hyperventilating subjects who maintained a sinusoidal breathing
pattern. The sinusoidal pattern, they reasoned, increased the
compression of tissues. The breathing pattern during lobeline challenge
was also more sinusoidal, as seen during exercise in horses
(2).
Based on our observations, one could potentially construct flowmetric
variables that discriminate obstruction from hyperpnea. Our use of area
differences (SFEint, SFIint) was one such
attempt. These variables indeed were more "refractory" to the
effects of hyperpnea and tachypnea.
In conclusion, a method that directly compares plethysmographic and
pneumotachographic flow was found to be both feasible and valid in the
horse for measurement of relative changes in lung mechanics because of
experimental bronchoconstriction or during bronchodilation of horses
with severe, recurrent airway obstruction. The effects of lung volume,
barometric pressure, and f (when combined) require further observation
in a physical model of the measurement system and in the horse. The
advantages of this system for testing airway reactivity and
bronchodilator effects include its noninvasive platform and the lack of
requirement for energy input (pressure, loudspeakers) to drive the
system, making the system potentially portable.
| |
FOOTNOTES |
Address for reprint requests and other correspondence: A. Hoffman, Associate Professor, Large Animal Medicine, 200 Westboro Rd.,
North Grafton, MA 01536 (E-mail: andrew.hoffman{at}tufts.edu).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 6 March 2001; accepted in final form 27 July 2001.
| |
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ABSTRACT
INTRODUCTION
