Changes of respiratory input impedance during breathing in humans M. CAUBERGHS AND K. P. VAN DE WOESTIJNE Laboratorium moor Pneumolugie, Uniuersitair Ziekenhuis CAUBERGHS, M., AND K. P. VAN DE WOESTIJNE. Changes of respiratory input impedance during breathing in humans. J.
Appl. Physiol. 73(6): 23552362,1992.--Changes of total respiratory resistance (Rrs) and reactance (Xrs) were studied between 8 and 32 Hz at five momentsduring the respiratory cycle in healthy adults (group A) and children (group B) and in patients with chronic obstructive lung disease(group C) and with upper airway obstruction (group D). Two forced oscillation techniqueswere used:the conventional oneand the headgenerator, with the oscillationsapplied at the mouth and around the head of the subject,respectively. Both techniquesyielded similar results. Rrs is lowest during the transition from inspiration to expiration and highest in the courseof expiration, except in group D. Mean Xrs is highest at the transitions from inspiration to expiration or vice versa and lowest during expiration, except in group D. In groups C and D, the increasesof Rrs are accompaniedby a more pronounced negative frequency dependenceof Rrs. The variations of Rrs and Xrs appear to be markedly flow dependentand may be a consequenceof the interaction of breathing with oscillatory flows. forced oscillation technique; head generator; upper airway obstruction; chronic obstructive pulmonary disease
WHEN THE impedance
of the respiratory system (Zrs) is measured by means of a forced oscillation technique (12, 13) the investigated subject is usually allowed to breathe quietly as the oscillations are applied. This avoids unpredictable movements of the glottis during the voluntary performance of an apnea. Because the.measurement of Zrs, as obtained from spectral techniques, is based on averages over a period of several breaths, it will reflect the mean characteristics of the respiratory system over such a period. However, cyclic changes of Zrs during one respiratory cycle should be expected. Indeed, the dimensions of extra- and intrathoracic airway vary periodically during breathing (7); the glottis aperture widens during inspiration and narrows during expiration (1, 2, 6, 19), and the elastic properties of the lungs and chest wall vary with changes in lung volumes. It is possible, by slightly modifying the technique, to perform determinations at given moments during the respiratory cycle. Selective sampling of forced random noise was realized by Michaelson et al. (13) at functional residual capacity and during early inspiration and at midinspiration and midexpiration by Miller and Pimmel (14). Michaelson et al. investigated spontaneously breathing healthy subjects and patients with chronic obstructive pulmonary disease (COPD) within a frequency range of 3-45 Hz, and Miller and Pimmel investigated healthy nonsmokers from 5 to 25 Hz. The data were analyzed by means of a second0161-7567/92
$2.00 Copyright
Gasthuisberg, B-3000 Louuain,
Belgium
order resistance-inertance-compliance model. Whereas the variations of the real part of Zrs, respiratory system resistance (Rrs), during the respiratory cycle differed from subject to subject in the study by Michaelson et al., the resonant frequency was uniformly higher at midinspiration, compared with functional residual capacity, partly because of a fall in inertance in the normal subjects. Miller and Pimmel(14) observed a statistically significant decrease in Rrs and in total respiratory compliance and a significant increase in inertance during inspiration with respect to expiration. An increase of Rrs during expiration, compared with inspiration, was documented in healthy subjects at 3 Hz by England et al. (6) and at 10 Hz by Davidson et al. (4) and Sekisawa et al. (18) In addition to those variations related to the phase of the breathing cycle, a specific influence of the magnitude of respiratory flow on Rrs has been described. Peslin et al. (16) observed cyclical changes of Rrs, determined at one single frequency, with respiratory flow. The latter results were confirmed by Davidson et al. (4) in patients with airflow obstruction. Rrs, measured at the frequency of 10 Hz, was found to increase with the amplitude of flow, whether inspiratory or expiratory. Recently, Peslin et al. (17) analyzed the flow and volume dependence of Rrs separately during inspiration and expiration at 10, 20, and 30 Hz in healthy subjects. Rrs was markedly flow dependent, particularly at higher frequencies and during expiration. In these various studies, except for the studies of Peslin et al. (16, 17), the impedance values were obtained from forced oscillations applied at the mouth of the investigated subjects. The latter measurements are fraught with a systematic bias due to the shunt characteristics of the upper airway (15). We thought it might be interesting to reinvestigate the variations of Zrs during the breathing cycle, with use of a technique correcting for this bias, and in groups of human subjects with widely divergent values of airflow resistance. MATERIAL
AND METHODS
Satisfactory data were obtained from 7 healthy adults, 5 children (ages 6-8 yr), 5 patients with upper airway obstruction, and 13 patients with COPD. Among the patients with upper airway obstruction, two suffered from a fixed stenosis of the trachea due to a carcinoma and following tracheostomy, respectively, two suffered from a mainly inspiratory stenosis due to scarring of the glottis and unilateral paralysis of a vocal cord, and one suffered from an expiratory stenosis caused by compression of the
0 1992 the American
Physiological
Society
2355
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2356
RESPIRATORY
I
I
I
8
16
24
IMPEDANCE
1
32 Hz
DURING
BREATHING
I
I
1
8
16
24
I
32Hr
1
1
1
I
8
16
24
1 32 Hz
FIG. 1. Mean respiratory system resistance (Rrs; tep) and reactance (Xrs; bottom) values as a function of oscillatory frequency obtained in 7 healthy adults. Numbers (L-5) accompanying curves correspond to 5 distinct moments during breathing cycle: 1, transition from expiration to inspiration (solid line); 2, maximal inspiratory flow (dotted line); 3, transition from inspiration to expiration (dash-dot line); 4, maximal expiratory flow (dashed line); 5, half expiration (dash-double dot line). A: head generator technique. B: conventional technique.
trachea by a goiter. In the patients with COPD, the forced expiratory volume in 1 s was 40 and 70% of expected in 11 and 2 patients, respectively. All subjects
were instructed to breathe quietly during the measurements. Forced pseudorandom oscillations with a frequency content ranging from 2 to 32 Hz (by increments of 2 Hz) were applied at the mouth using, in a random order, both the conventional
and the head generator technique as
described previously
by Cauberghs and Van de Woesti-
jine (3). The resulting pressure and flow signals, recorded at the mouth during 32 s, were digitized at 128 Hz and
stored. An average respiratory input impedance and coherence function were then calculated. If the value of the latter did not exceed 0.95 at all frequencies above 10 Hz, the data were rejected. The measurements were repeated until at least three acceptable data sets were obtained for both techniques. If this was not feasible, despite repeated attempts, the subject was not included in the study. From each data set of pressure and airflow values, respiratory airflow vs. time was obtained over the period of 32 s by use of a moving average filter, with a period of 0.5 s, as described by Horowitz et al. (9). Briefly, a window of 0.5 s (i.e., the period of the fundamental oscillatory frequency) was moved along the recorded values of airflow and the mean of all 64 values within this window was calculated at each position of the latter. Those mean values correspond to respiratory airflow. Subtrkcting this respiratory component, point by point, from the recorded flow values yielded the oscillatory component of flow. The same filtering was used to split recorded pressure values into their breathing and oscillatory components.
To investigate the variability of Zrs within the respiratory cycle, five distinct moments within the breathing cycle were defined: 1) transition from expiration to inspiration: the lung volume is minimal; 2) maximal inspiratory flow; 3) transition from inspiration to expiration: lung volume is maximal; 4) maximal expiratory flow; and 5) halfway down the expiration. For each subject each of those five moments occurred several times, depending on the breathing frequency and the number of accepted trials. If one of those moments could not be distinguished clearly from the tracing of airflow vs. time, the corre-
sponding respiratory cycle was discarded. For each time block of 0.5 s centered around the selected moment, a spectral analysis of the corresponding oscillatory components of pressure apd flow data was performed. The data were averaged over all appropriate time blocks. The threshold value that the coherence function had to reach for accepting the impedance values was calculated as described by Franken et al. (8). This threshold is defined by the amount of spectra that have been averaged, the input impedance of the measuring device (different for both techniques), the input impedance of the respiratory system, the variability of the spectral composition of the respiratory flow at each of the five moments within the breathing cycle, and finally the maximum bias (5%) that one allows on the estimation of both real (Rrs) and imaginary part [respiratory system reactance (Xrs)] of the input impedance. On the data of Rrs and Xrs vs. oscillatory frequency, a fourth-order polynomial was fitted that incorporated all frequencies at which the coherence function exceeded the threshold value. From the values of coefficients of -this polynomial a mean value of the level (Rrs, Xrs) and of Rrs and Xrs frequency curves the slope (Rrs (l), &P)
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
RESPIRATORY
IMPEDANCE
DURING
2357
BREATHING
8
16
24
32Hz
.2
.Q
‘: 2
.
9.4 I
8 FIG. 2. Mean Rrs (top) See Fig. 1 for details.
and Xrs (bottom)
16
24
values
as a function
32 Hz
of oscillatory
was calculated in the frequency interval of 8-32 Hz (II). Values of level and slope for all subjects of the same group (healthy adults, healthy children) were averaged. For both measuring techniques, and for each of the four groups of subjects, differences in level and slope of Rrs and Xrs between the five distinct moments within the respiratory cycle were analyzed by means of a Duncan’s multiple range test. To investigate the influence of the duration of the time blocks (0.5 s) on the measurements we modified the excitation signal. A pseudorandom signal containing only the frequencies 8,16,24, and 32 Hz was applied in the head generator technique. Pressure and airflow signals were digitized at a frequency of 512 Hz. This allowed us to estimate Rrs and Xrs at a particular moment in the breathing cycle over a period of 0.125 s. The influence of actual volume and airflow on instantaneous Rrs and Xrs at times 2 and 4 of the respiratory cycle was investigated separately in five healthy adults, four patients with COPD, and three patients with upper airway obstruction. In those subjects, a multiple regression was calculated between level and slope of Rrs or Xrs, measured at each of these moments, and corresponding values of flow (V) and volume (V) obtained from the investigated breathing cycles Rrs(Xrs)
or Rr&,Xrs(‘))
= av + bV + c
As a reference value for V, mean midtidal volume was used. The individual values of the coefficients of the regression were pooled to evaluate their statistical significance within each group of subjects.
8
frequency
obtained
1
1
16
24
in 5 healthy
1
32Hr
children.
RESULTS
Results in the four groups of subjects. The variations of average values of Rrs and Xrs, expressed as a function of frequency, during a respiratory cycle are represented for each of the four groups in Figs. lA-4A concerning the results obtained with the head generator and in Figs. 1% 4B for the conventional technique. Keeping only the statistically significant differences into account, the observed variations of Rrs and Xrs can be described as follows. For the healthy adults (Fig. l), Rrs shows a slightly positive frequency dependence, which does not vary during the respiratory cycle. Rrs during expiration (times 4 and 5) is on the average significantly higher than during the transitions I and 3. The slope of Xrs is similar from times 1 to 5, but the mean value of Xrs is less at maximal expiratory flow (time 4) than at time 1. With the conventional technique, Rrs at times 4 and 5 is larger than at time 3. This increase is accompanied by a negative frequency dependence at times 4 and 5. For Xrs, the average values at time 3 (or times 3 and 1) differ from those at times 4 and 5 (time 4, respectively). The slopes are similar. In children (Fig. 2) resistance values are higher than in adults; Rrs is on the average higher during expiration (time 4) than at time 3. The slope of Rrs vs. frequency is slightly negative and does not change significantly during the breathing cycle. With the conventional technique both average and slope of Rrs are similar from times l-5. Xrs, measured with the head generator, is less positive at times 4 and 2 than at time 1 and has a less pronounced
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2358
RESPIRATORY
IMPEDANCE
DURING
/ 5
5
l* I 8
I
1
I
16
24
32
Hz
BREATHING
t
I
1
1
8
16
24
32
I 16
I 24
1 32
/’ I 8
Hz
3. Mean Rrs (top) and Xrs (bottom) values as a function of oscillatory frequency obtained in 13 patients with chronic obstructive pulmonary disease. See Fig. 1 for details. FIG.
slope at times 4 and 5 than at time 2. With the conventional technique Xrs at times 1 and 3 is higher than at tl’me 4, and the slope at time 3 is steeper than at times 1 and 5. In people with COPD (Fig. 3) there is a marked negative frequency dependence of Rrs; the Xrs frequency curves are shifted to the right compared with healthy adults. In both head generator and conventional techniques, Rrs at times 4 and 5 is larger than at time 3 and its frequency dependence is more negative at time 5 than at times 2 and 3. Xrs at times 4 and 5 (or 5) is less than at times 3 (2 and 3, respectively). The slope of Xrs is steeper at time 5 than at times 2 and 3 with the head generator and than at times 1 to 4 with the conventional technique. In upper airway obstruction (Fig. 4), there is a slightly negative frequency dependence of Rrs, also with the head generator. The variability of the data is larger than in the &her groups: the differences between Rrs and Xrs at various times in the breathing cycle, although on the average larger, are less significant. Mean Rrs is significantly larger at time 2 than at flow zero (times I and 3). The mean values and the slopes of Xrs do not differ significantly. With the conventional technique only the mean values of Rrs at times 2 vs, 3 and of Xrs at time 3 vs. 4 and 5 are significantly different. Influence of duration of time ~Z~cFzs.In two adults, one healthy subject and one patient with moderate asthma, we compared the values of Rrs and Xrs determined at given miments in the respiratory cycle (times L-5) when the data were sampled over a period of 0.5 or 0.125 s. Figure 5 shows that-sampling over a longer perio d of time leads to some underestimation of the vari ation s of Rrs:
the largest values are reduced and the smallest are increased. The underestimation is small, however, and even less for Xrs (not shown). Influence of airflow on instantaneous values of Rrs and Xrs. The influence of respiratory flow on the instantaneous values of Rrs and Xrs (head generator) was evaluated by investigating the relationship between the latter values and the spontaneous variations of flow at two moments of the respiratory cycle: maximal inspiration (time 2) and expiration (time 4). Table 1 shows for 12 subjects the regression coefficients between flow (taking into account a possible influence of volume) and the mean level and slope of the Rrs and Xrs frequency curves. Only the statistically significant coefficients (P s 0.05) are indicated. In healthy subjects as well as in COPD patients, the mean level of Rrs tends to increase with the absolute value of flow, whereas the mean level and slope of Xrs tend to decrease. This is observed both at times 2 and 4. The frequency dependence of Rrs is not affected by flow in most subjects. Examples of the relationship between mean level of Rrs or Xrs and corresponding flow are shown in Fig. 6 for a healthy adult and a COPD patient. In patients with upper airway obstruction only a few regression coefficients reached the limit of statistical significance, likely because of the variability of the impedance measurements. DISCUSSION
Although the variations of Rrs and Xrs during the breathing cycle are not identical among the four groups of subjects, a common pattern can be noticed. Rrs is sys-
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
RESPIRATORY
A
IMPEDANCE
DURING
B
:.. : : .... .,..= ..
1.2 2
2359
BREATHING
.8
l .
n P !&
5 4
.8
r
1 3
E a .4*
c
.l'
.o-
3
1
I
8
10
24
;I
16
1 32
Hz
.l
.o
-a-
--
r l
t s x
3 5
E
-.2 4 2
3 1
-.0.42 I
-. 4
2 4 5
241
161
;,
i2Hz
2b
1
32
FIG.
upper
4. Mean Rrs (top) and Xrs (bottom) values airway obstruction. See Fig. 1 for details.
as a function
of oscillatory
tematically lowest at the transition between inspiration and expiration (time 3) and highest during expiration (times 4 and 5), except in the presence of upper airway obstruction. Then, Rrs is larger at top inspiratory flow (time 2) than during expiration. These changes are mirrored in the variations of Xrs; the latter is less posi-
frequency
obtained
in 5 patients
Hz
with
tive during expiration (times 4 and/or 5) than at the transition from expiration to inspiration (time 1) or from inspiration to expiration (time 3). In upper airway obstruction (head generator) Xrs is lowest at time 2. However, this difference is not statistically significant. The fact that Rrs is larger and Xrs lower during expiration at
8
A
.8
.8
5 .6 4
.4
t
1
I
0
16
24
1
32 Hz
r;
16
l
-1
24
32
Hz
5. Rrs as a function of oscillatory frequency in two subjects. A: 1 healthy subject breathing at a frequency of 12 breathsjmin. B: 1 obstructive patient breathing at 22 breathsimin. Numbers l-5 indicate corresponding moments during breathing cycle. Processing of signals has been performed in 2 ways: using time blocks of 0.5 (solid lines) and 0.125 s (dotted lines). FIG.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2360
RESPIRATORY A
IMPEDANCE
0.51
0.1:
0.2
0.2
0.4
0.4
0.6
0.6
0.8
0.8
1.0
LO
1.2
1.2
i (I ’ s-l) FIG. 6. Cycle-per-cycle values of mean level of Rrs and Xrs in a healthy adult (A) and a patient with COPD (B) as a function of absolute values of respiratory flow at two times during the breathing cycles. l , Maximal inspiratory flow; 0, maximal expiratory flow.
DURING
BREATHING
way shunt in parallel with Zrs (13). This shunt also explains the negative frequency dependence of Rrs observed in healthy adults at times 4 and 5. We were surprised to observe a negative frequency dependence of Rrs and a shift to the right of the Xrs frequency curves with increased resonant frequency in patients with upper airway obstruction and also when the upper airway shunt was dealt with by means of the head generator technique. A negative frequency dependence of Rrs and increase in resonant frequency was observed in all patients of this group, particularly at times 2,4, and 5, i.e., in the course of inspiration and expiration. The TABLE 1. Individual and common regression coefficients (P s 0.05) of mean level and slope of instuntuneous respiratory resistance and reactance vs. corresponding flow at times 2 and 4 of the respiratory cycle in healthy subjects and patients with COPD and upper airway obstruction v,
R’“‘,
ml/s
x10
Rrd’), x1o-4
Xrs,
X1O-4
Xrdl’, x1o-4
Time2
Healthy subjects
maximal expiratory flow or halfway throughout the expiration1 and, in upper airway obstruction, at maximal inspiratory flow than at times of minimal flow (times 1 and 3) points to a flow dependence of the values of Rrs and Xrs. A volume dependence is not marked. Rrs or Xrs do not differ significantly when the transitions from inspiration to expiration &me 3) or from expiration to inspiration (time I) are compared. Still, Rrs tends to be less at time 3 than at time 1. The influence of respiratory flow on the values of Rrs and Xrs is substantiated by the study of the relationship between the spontaneous fluctuations of flow and the corresponding values of Rrs and Xrs at two moments in the breathing cycle (times 2 and 4). Mean levels of Rrs and Xrs increase and decrease, respectively, at larger flows in healthy subjects and patients with COPD. Simultaneously, the slope of the Xrs frequency curve tends to decrease. However, all variations of Rrs and Xrs cannot be reduced to an effect of airflow. Except in the group of upper airway obstruction, Rrs values are on the average higher and Xrs values less during expiration (time 4) than at a similar moment during inspiration (time 2; Figs. l--3), despite the fact that maximal flows are generally less during expiration than during inspiration (Table 1). This is illustrated in Fig. 6 for separate measurements from consecutive breathing cycles and confirms the conclusion of others (4,6,17,18) that, besides the amplitude of flow, the phase of the breathing cycle influences the values of Rrs (and Xrs). With respect to the head generator, the conventional technique yields similar variations of Rrs and Xrs during breathing. However, the variations are less pronounced. This smoothing effect, especially marked in upper airway obstruction, is because of the influence of the upper air’ A decrease of the values of Xrs during expiration results in an apparent decrease of inertance, calculated from the Xrs frequency curve assuming a one-alveolar model. This might explain the findings of Miller and Pimmel (14).
1 2 3 4 5
-0.339”
755-t-113
6541-49 718t163 5861~54 781+105
Common
-0.304
3.249+
0.095t
0.829
0.559* -1.029* -0.036* -0.488t -0.425
COPDpatients 933+97 924k-45
6 7 8
885_+50
9
1,011+80
6.403t
Common Upper airway patients 10 11 12
556+26 564+37 63Ok26
-1.862t
-8.923 -9.415 Time
2 3 4 5
-3.430 -1.328t
3.0897 -2.085*
Common Healthy subjects 1
-1.748.t -0.210*
-2.517.f
4
-723kll.9 -511+53
-479t98 -488~180 -580288
Common
0.204
-4.839t -2.397*
0.101*
-1.156”
1.320? 0.814-f
0.096
0.265
0.080
COPD patients 6 7 8
9
-943t114 -441+29
11 12
1.962* -0.594 2.390
-1.016
-606-t22 -716t30
Common Upper airway patients 10
1.753
5.255 -556t42 -403t53 -564t38
-14.742
Values are means t SD. Common, values of the common fegression line of the -group (given only when statistically significant), V, respiratory flow; Rrs, XPS, level of respiratory system resistance and reactance, respectively; Rrs (l) , Xr#), slope of respiratory system resistance and reactance, respectively. * P < 0.01; t P < 0.001.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
MG5YlfCA'l'UK.
Y llVlk’~UAN
L;r;
A
U UMN
ti
l5fCEA’l’HlN
ti
Z;Jbl
B 1.5 R.V.
0
33 yrs
1.0
.5
.O 8
16
24
32 Hz
8
16
24
32
Hz
16
24
32 Hz
-. 5
t
1
1
8
16
24
I
32 Hz
8
7. Rrs and Xrs values vs. frequency obtained with head generator in a healthy and during simulated upper airway obstruction (B) (see text). Numbers 1-5 correspond cycle.
adult during quiet breathing (A) to 5 moments within breathing
FIG.
average curves of Rrs and Xrs, obtained over a period of 32 s, i.e., over several breathing cycles, also demonstrated this phenomenon. We do not think that this is the result of an artifact or attributable to lower airway disease; none of these patients had a history of COPD. In addition, the phenomenon can be reproduced by asking healthy subjects to narrow voluntarily the glottis during breathing. In two of four subjects, this maneuver resulted in the appearance of a marked negative frequency dependence of Rrs mainly at times 2 and 4 and in a simultaneous shift to the right of the Xrs frequency curves (Fig. 7). In one subject, resistance simply increased without becoming frequency dependent, and in the other subject breathing became totally irregular. This suggests that 1) the findings in patients with upper airway obstruction are caused, indeed, by a narrowing of the upper airway; and 2) the increase of Rrs, the negative frequency dependence of Rrs, and the shift of the resonant frequency at times 2,4, and 5 in these subjects are a consequence of the influence of airflow on the values of Rrs and Xrs and are thus comparable to the flow-dependent changes in Rrs and Xrs observed in patients with COPD. In people with upper airway obstruction the effect of flow is more pronounced during inspiration; it is more prevailing during expiration in patients with COPD. The influence of a steady flow on the oscillatory impedance of the larynx has been studied on excised human larynx preparations by Jiang et al. (10). Superposition of
a steady flow on the forced oscillations, generated to determine the impedance of the larynx, results in an increase of resistance, a change of its frequency dependence (from positive to absent or even slightly negative), and a decrease of reactance mainly at higher frequencies. Although the mechanisms of the influence of steady flow on oscillatory resistance are not fully elucidated (5), the study on the excised larynx reproduces qualitatively the variations of Rrs and Xrs observed in the present study. Finally, one might wonder to what extent the changes of Rrs and Xrs observed during breathing are influenced by the fact that the computed values are not truly instantaneous but are sampled over a period of 0.5 s. This was investigated by reducing the sampling time to 0.125 s. Figure 5 shows that, as expected, a longer sampling period only reduces the actual variations of Rrs. This work was supported by a grant of the Fonds voor Geneeskundig Wetenschappelijk Onderzoek. Address for reprint requests: K. P. Van de Woestijne, Laboratorium voor Pneumologie, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Received
8 May
1991; accepted
in final
form
13 July
1992.
REFERENCES 1.
BAIER, H., A. WANNER, S.~ARZECKI,AND M. A. SACKNER. Relationships resistance
among glottis opening, respiratory flow and upper airway in humans. J. Appl. Physiol. 43: 603-611, 1977. 2. BRANCATISANO, T.,P.W. COLLETT,AND L.A. ENGEL. Respiratory
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2362
3, 4.
5.
6. 7. 8.
9.
10.
RESPIRATORY
IMPEDANCE
movements of the vocal cords. J. Appl. Physiol. 54: 1269-1276, 1983. CAUBERGHS, M., AND K. P. VAN DE W~ESTIJNE. Effect of upper airway shunt and series properties on respiratory impedance measurements. J. Appl. Physiol. 66: 2274-2279, 1989. DAVIDSON, R. N., C. A. GREIG, A. HUSSAIN, AND K. B. SAUNDERS. Within-breath changes of airway calibre in patients with airflow obstruction by continuous measurement of respiratory impedance. Br. J. Dis. Chest 80: 335-352, 1986, DORKIN, H. L., A. C. JACKSON, D. J. STRIEDER, AND S. V. DAWSON. Interaction of oscillatory and unidirectional flows in straight tubes and an airway cast. J. Appl. Physiol. 52: 1097-1105, 1982. ENGLAND, S. J., D. BARTLETT, JR., AND J. A. DAUBENSPECK. Influence of human vocal cord movements on airflow and resistance during eupnea. J. Appl. Physiol. 52: 773-779, 1982. FOUKE, J. M., A. D. WOLIN, K, P. STROHL, AND G. M. GALBRAITH. EIastic characteristics of the airway wall. J. Appl. Physiol. 66: 962967,1989* FRANKEN, H., J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Systematic and random errors in the determination of respiratory impedance by means of the forced oscillation technique: a theoretical study. IEEE Trans. Biomed. Eng. 30: 642-651,1983. HOROWITZ, J. G., S. D. SIEGEL, F. P. PRIMIANO, JR., AND E. H. CHESTER. Computation of respiratory impedance from forced sinusoidal oscillations during breathing. Comput. Biomed. Res. 16: 499521, 1983. JIANG, T. X., M. CAUBERGHS, AND K. P. VAN DE WOESTIJNE. Resistance and reactance of the excised human larynx, trachea and main bronchi. J. Apple. Physiol. 63: 17881795, 1987.
DURING
BREATHING
11. LANDSER, F, J., J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Normal values of total respiratory resistance and reactance determined by forced oscillations. Influence of smoking. Chest 81: 586591,1982. 12. LANDSER, F. J., J. NAGELS, M. DEMEDTS, L. BILLIET, AND K. P. VAN DE WOESTIJNE. A new method to determine frequency characteristics of the respiratory system. J. Appl. Physiol. 41: 101-106, 1976. 13. MICHAELSON, E. D., E. D. GRASSMAN, AND W. R. PETERS. Pulmonary mechanics by spectral analysis of forced random noise. J. Clin. Inuest. 56: 1210-1230, 1975. 14. MILLER, T. K,, AND R. L. PIMMEL. Forced noise mechanical parameters during inspiration and expiration. J. Appl. Physiol. 52: l53O1534, 1982. 15. PESLIN, R., C. DUVIVIER, J. DIDELON, AND C. GALLINA. Respiratory impedance measured with head generator to minimize upper airway shunt. J. Appl. Physiol. 59: 1790-1795, 1985. 16. PESLIN, R., T, HIXON, AND J. MEAD. Variations des resistances thoraco-pulmonaires au tours du cycle ventilatoire htudiees par methode d’oscillation. Bull. Physio-Path. Respir. 7: 173-186, 1971. 17. PESLIN, R., Y. YING, C. GALLINA, AND C. D~TVIVIER. Within-breath variations of forced oscillation resistance in healthy subjects. Eur. Respir. J. 5: 86-92, 1992. 18. SEKISAWA, K., H. SASAKI, AND T. TAKISHIMA. Laryngeal resistance immediately after panting in control and constricted airways. J. Appl. Physiol. 58: 1164-1169, 1985. 19. STANESCU, D. C., J. PATTIJN, J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Glottis opening and airway resistance. J. Appl. Physiol. 32: 460-466, 1972.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
Appl. Physiol. 73(6): 23552362,1992.--Changes of total respiratory resistance (Rrs) and reactance (Xrs) were studied between 8 and 32 Hz at five momentsduring the respiratory cycle in healthy adults (group A) and children (group B) and in patients with chronic obstructive lung disease(group C) and with upper airway obstruction (group D). Two forced oscillation techniqueswere used:the conventional oneand the headgenerator, with the oscillationsapplied at the mouth and around the head of the subject,respectively. Both techniquesyielded similar results. Rrs is lowest during the transition from inspiration to expiration and highest in the courseof expiration, except in group D. Mean Xrs is highest at the transitions from inspiration to expiration or vice versa and lowest during expiration, except in group D. In groups C and D, the increasesof Rrs are accompaniedby a more pronounced negative frequency dependenceof Rrs. The variations of Rrs and Xrs appear to be markedly flow dependentand may be a consequenceof the interaction of breathing with oscillatory flows. forced oscillation technique; head generator; upper airway obstruction; chronic obstructive pulmonary disease
WHEN THE impedance
of the respiratory system (Zrs) is measured by means of a forced oscillation technique (12, 13) the investigated subject is usually allowed to breathe quietly as the oscillations are applied. This avoids unpredictable movements of the glottis during the voluntary performance of an apnea. Because the.measurement of Zrs, as obtained from spectral techniques, is based on averages over a period of several breaths, it will reflect the mean characteristics of the respiratory system over such a period. However, cyclic changes of Zrs during one respiratory cycle should be expected. Indeed, the dimensions of extra- and intrathoracic airway vary periodically during breathing (7); the glottis aperture widens during inspiration and narrows during expiration (1, 2, 6, 19), and the elastic properties of the lungs and chest wall vary with changes in lung volumes. It is possible, by slightly modifying the technique, to perform determinations at given moments during the respiratory cycle. Selective sampling of forced random noise was realized by Michaelson et al. (13) at functional residual capacity and during early inspiration and at midinspiration and midexpiration by Miller and Pimmel (14). Michaelson et al. investigated spontaneously breathing healthy subjects and patients with chronic obstructive pulmonary disease (COPD) within a frequency range of 3-45 Hz, and Miller and Pimmel investigated healthy nonsmokers from 5 to 25 Hz. The data were analyzed by means of a second0161-7567/92
$2.00 Copyright
Gasthuisberg, B-3000 Louuain,
Belgium
order resistance-inertance-compliance model. Whereas the variations of the real part of Zrs, respiratory system resistance (Rrs), during the respiratory cycle differed from subject to subject in the study by Michaelson et al., the resonant frequency was uniformly higher at midinspiration, compared with functional residual capacity, partly because of a fall in inertance in the normal subjects. Miller and Pimmel(14) observed a statistically significant decrease in Rrs and in total respiratory compliance and a significant increase in inertance during inspiration with respect to expiration. An increase of Rrs during expiration, compared with inspiration, was documented in healthy subjects at 3 Hz by England et al. (6) and at 10 Hz by Davidson et al. (4) and Sekisawa et al. (18) In addition to those variations related to the phase of the breathing cycle, a specific influence of the magnitude of respiratory flow on Rrs has been described. Peslin et al. (16) observed cyclical changes of Rrs, determined at one single frequency, with respiratory flow. The latter results were confirmed by Davidson et al. (4) in patients with airflow obstruction. Rrs, measured at the frequency of 10 Hz, was found to increase with the amplitude of flow, whether inspiratory or expiratory. Recently, Peslin et al. (17) analyzed the flow and volume dependence of Rrs separately during inspiration and expiration at 10, 20, and 30 Hz in healthy subjects. Rrs was markedly flow dependent, particularly at higher frequencies and during expiration. In these various studies, except for the studies of Peslin et al. (16, 17), the impedance values were obtained from forced oscillations applied at the mouth of the investigated subjects. The latter measurements are fraught with a systematic bias due to the shunt characteristics of the upper airway (15). We thought it might be interesting to reinvestigate the variations of Zrs during the breathing cycle, with use of a technique correcting for this bias, and in groups of human subjects with widely divergent values of airflow resistance. MATERIAL
AND METHODS
Satisfactory data were obtained from 7 healthy adults, 5 children (ages 6-8 yr), 5 patients with upper airway obstruction, and 13 patients with COPD. Among the patients with upper airway obstruction, two suffered from a fixed stenosis of the trachea due to a carcinoma and following tracheostomy, respectively, two suffered from a mainly inspiratory stenosis due to scarring of the glottis and unilateral paralysis of a vocal cord, and one suffered from an expiratory stenosis caused by compression of the
0 1992 the American
Physiological
Society
2355
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2356
RESPIRATORY
I
I
I
8
16
24
IMPEDANCE
1
32 Hz
DURING
BREATHING
I
I
1
8
16
24
I
32Hr
1
1
1
I
8
16
24
1 32 Hz
FIG. 1. Mean respiratory system resistance (Rrs; tep) and reactance (Xrs; bottom) values as a function of oscillatory frequency obtained in 7 healthy adults. Numbers (L-5) accompanying curves correspond to 5 distinct moments during breathing cycle: 1, transition from expiration to inspiration (solid line); 2, maximal inspiratory flow (dotted line); 3, transition from inspiration to expiration (dash-dot line); 4, maximal expiratory flow (dashed line); 5, half expiration (dash-double dot line). A: head generator technique. B: conventional technique.
trachea by a goiter. In the patients with COPD, the forced expiratory volume in 1 s was 40 and 70% of expected in 11 and 2 patients, respectively. All subjects
were instructed to breathe quietly during the measurements. Forced pseudorandom oscillations with a frequency content ranging from 2 to 32 Hz (by increments of 2 Hz) were applied at the mouth using, in a random order, both the conventional
and the head generator technique as
described previously
by Cauberghs and Van de Woesti-
jine (3). The resulting pressure and flow signals, recorded at the mouth during 32 s, were digitized at 128 Hz and
stored. An average respiratory input impedance and coherence function were then calculated. If the value of the latter did not exceed 0.95 at all frequencies above 10 Hz, the data were rejected. The measurements were repeated until at least three acceptable data sets were obtained for both techniques. If this was not feasible, despite repeated attempts, the subject was not included in the study. From each data set of pressure and airflow values, respiratory airflow vs. time was obtained over the period of 32 s by use of a moving average filter, with a period of 0.5 s, as described by Horowitz et al. (9). Briefly, a window of 0.5 s (i.e., the period of the fundamental oscillatory frequency) was moved along the recorded values of airflow and the mean of all 64 values within this window was calculated at each position of the latter. Those mean values correspond to respiratory airflow. Subtrkcting this respiratory component, point by point, from the recorded flow values yielded the oscillatory component of flow. The same filtering was used to split recorded pressure values into their breathing and oscillatory components.
To investigate the variability of Zrs within the respiratory cycle, five distinct moments within the breathing cycle were defined: 1) transition from expiration to inspiration: the lung volume is minimal; 2) maximal inspiratory flow; 3) transition from inspiration to expiration: lung volume is maximal; 4) maximal expiratory flow; and 5) halfway down the expiration. For each subject each of those five moments occurred several times, depending on the breathing frequency and the number of accepted trials. If one of those moments could not be distinguished clearly from the tracing of airflow vs. time, the corre-
sponding respiratory cycle was discarded. For each time block of 0.5 s centered around the selected moment, a spectral analysis of the corresponding oscillatory components of pressure apd flow data was performed. The data were averaged over all appropriate time blocks. The threshold value that the coherence function had to reach for accepting the impedance values was calculated as described by Franken et al. (8). This threshold is defined by the amount of spectra that have been averaged, the input impedance of the measuring device (different for both techniques), the input impedance of the respiratory system, the variability of the spectral composition of the respiratory flow at each of the five moments within the breathing cycle, and finally the maximum bias (5%) that one allows on the estimation of both real (Rrs) and imaginary part [respiratory system reactance (Xrs)] of the input impedance. On the data of Rrs and Xrs vs. oscillatory frequency, a fourth-order polynomial was fitted that incorporated all frequencies at which the coherence function exceeded the threshold value. From the values of coefficients of -this polynomial a mean value of the level (Rrs, Xrs) and of Rrs and Xrs frequency curves the slope (Rrs (l), &P)
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
RESPIRATORY
IMPEDANCE
DURING
2357
BREATHING
8
16
24
32Hz
.2
.Q
‘: 2
.
9.4 I
8 FIG. 2. Mean Rrs (top) See Fig. 1 for details.
and Xrs (bottom)
16
24
values
as a function
32 Hz
of oscillatory
was calculated in the frequency interval of 8-32 Hz (II). Values of level and slope for all subjects of the same group (healthy adults, healthy children) were averaged. For both measuring techniques, and for each of the four groups of subjects, differences in level and slope of Rrs and Xrs between the five distinct moments within the respiratory cycle were analyzed by means of a Duncan’s multiple range test. To investigate the influence of the duration of the time blocks (0.5 s) on the measurements we modified the excitation signal. A pseudorandom signal containing only the frequencies 8,16,24, and 32 Hz was applied in the head generator technique. Pressure and airflow signals were digitized at a frequency of 512 Hz. This allowed us to estimate Rrs and Xrs at a particular moment in the breathing cycle over a period of 0.125 s. The influence of actual volume and airflow on instantaneous Rrs and Xrs at times 2 and 4 of the respiratory cycle was investigated separately in five healthy adults, four patients with COPD, and three patients with upper airway obstruction. In those subjects, a multiple regression was calculated between level and slope of Rrs or Xrs, measured at each of these moments, and corresponding values of flow (V) and volume (V) obtained from the investigated breathing cycles Rrs(Xrs)
or Rr&,Xrs(‘))
= av + bV + c
As a reference value for V, mean midtidal volume was used. The individual values of the coefficients of the regression were pooled to evaluate their statistical significance within each group of subjects.
8
frequency
obtained
1
1
16
24
in 5 healthy
1
32Hr
children.
RESULTS
Results in the four groups of subjects. The variations of average values of Rrs and Xrs, expressed as a function of frequency, during a respiratory cycle are represented for each of the four groups in Figs. lA-4A concerning the results obtained with the head generator and in Figs. 1% 4B for the conventional technique. Keeping only the statistically significant differences into account, the observed variations of Rrs and Xrs can be described as follows. For the healthy adults (Fig. l), Rrs shows a slightly positive frequency dependence, which does not vary during the respiratory cycle. Rrs during expiration (times 4 and 5) is on the average significantly higher than during the transitions I and 3. The slope of Xrs is similar from times 1 to 5, but the mean value of Xrs is less at maximal expiratory flow (time 4) than at time 1. With the conventional technique, Rrs at times 4 and 5 is larger than at time 3. This increase is accompanied by a negative frequency dependence at times 4 and 5. For Xrs, the average values at time 3 (or times 3 and 1) differ from those at times 4 and 5 (time 4, respectively). The slopes are similar. In children (Fig. 2) resistance values are higher than in adults; Rrs is on the average higher during expiration (time 4) than at time 3. The slope of Rrs vs. frequency is slightly negative and does not change significantly during the breathing cycle. With the conventional technique both average and slope of Rrs are similar from times l-5. Xrs, measured with the head generator, is less positive at times 4 and 2 than at time 1 and has a less pronounced
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2358
RESPIRATORY
IMPEDANCE
DURING
/ 5
5
l* I 8
I
1
I
16
24
32
Hz
BREATHING
t
I
1
1
8
16
24
32
I 16
I 24
1 32
/’ I 8
Hz
3. Mean Rrs (top) and Xrs (bottom) values as a function of oscillatory frequency obtained in 13 patients with chronic obstructive pulmonary disease. See Fig. 1 for details. FIG.
slope at times 4 and 5 than at time 2. With the conventional technique Xrs at times 1 and 3 is higher than at tl’me 4, and the slope at time 3 is steeper than at times 1 and 5. In people with COPD (Fig. 3) there is a marked negative frequency dependence of Rrs; the Xrs frequency curves are shifted to the right compared with healthy adults. In both head generator and conventional techniques, Rrs at times 4 and 5 is larger than at time 3 and its frequency dependence is more negative at time 5 than at times 2 and 3. Xrs at times 4 and 5 (or 5) is less than at times 3 (2 and 3, respectively). The slope of Xrs is steeper at time 5 than at times 2 and 3 with the head generator and than at times 1 to 4 with the conventional technique. In upper airway obstruction (Fig. 4), there is a slightly negative frequency dependence of Rrs, also with the head generator. The variability of the data is larger than in the &her groups: the differences between Rrs and Xrs at various times in the breathing cycle, although on the average larger, are less significant. Mean Rrs is significantly larger at time 2 than at flow zero (times I and 3). The mean values and the slopes of Xrs do not differ significantly. With the conventional technique only the mean values of Rrs at times 2 vs, 3 and of Xrs at time 3 vs. 4 and 5 are significantly different. Influence of duration of time ~Z~cFzs.In two adults, one healthy subject and one patient with moderate asthma, we compared the values of Rrs and Xrs determined at given miments in the respiratory cycle (times L-5) when the data were sampled over a period of 0.5 or 0.125 s. Figure 5 shows that-sampling over a longer perio d of time leads to some underestimation of the vari ation s of Rrs:
the largest values are reduced and the smallest are increased. The underestimation is small, however, and even less for Xrs (not shown). Influence of airflow on instantaneous values of Rrs and Xrs. The influence of respiratory flow on the instantaneous values of Rrs and Xrs (head generator) was evaluated by investigating the relationship between the latter values and the spontaneous variations of flow at two moments of the respiratory cycle: maximal inspiration (time 2) and expiration (time 4). Table 1 shows for 12 subjects the regression coefficients between flow (taking into account a possible influence of volume) and the mean level and slope of the Rrs and Xrs frequency curves. Only the statistically significant coefficients (P s 0.05) are indicated. In healthy subjects as well as in COPD patients, the mean level of Rrs tends to increase with the absolute value of flow, whereas the mean level and slope of Xrs tend to decrease. This is observed both at times 2 and 4. The frequency dependence of Rrs is not affected by flow in most subjects. Examples of the relationship between mean level of Rrs or Xrs and corresponding flow are shown in Fig. 6 for a healthy adult and a COPD patient. In patients with upper airway obstruction only a few regression coefficients reached the limit of statistical significance, likely because of the variability of the impedance measurements. DISCUSSION
Although the variations of Rrs and Xrs during the breathing cycle are not identical among the four groups of subjects, a common pattern can be noticed. Rrs is sys-
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
RESPIRATORY
A
IMPEDANCE
DURING
B
:.. : : .... .,..= ..
1.2 2
2359
BREATHING
.8
l .
n P !&
5 4
.8
r
1 3
E a .4*
c
.l'
.o-
3
1
I
8
10
24
;I
16
1 32
Hz
.l
.o
-a-
--
r l
t s x
3 5
E
-.2 4 2
3 1
-.0.42 I
-. 4
2 4 5
241
161
;,
i2Hz
2b
1
32
FIG.
upper
4. Mean Rrs (top) and Xrs (bottom) values airway obstruction. See Fig. 1 for details.
as a function
of oscillatory
tematically lowest at the transition between inspiration and expiration (time 3) and highest during expiration (times 4 and 5), except in the presence of upper airway obstruction. Then, Rrs is larger at top inspiratory flow (time 2) than during expiration. These changes are mirrored in the variations of Xrs; the latter is less posi-
frequency
obtained
in 5 patients
Hz
with
tive during expiration (times 4 and/or 5) than at the transition from expiration to inspiration (time 1) or from inspiration to expiration (time 3). In upper airway obstruction (head generator) Xrs is lowest at time 2. However, this difference is not statistically significant. The fact that Rrs is larger and Xrs lower during expiration at
8
A
.8
.8
5 .6 4
.4
t
1
I
0
16
24
1
32 Hz
r;
16
l
-1
24
32
Hz
5. Rrs as a function of oscillatory frequency in two subjects. A: 1 healthy subject breathing at a frequency of 12 breathsjmin. B: 1 obstructive patient breathing at 22 breathsimin. Numbers l-5 indicate corresponding moments during breathing cycle. Processing of signals has been performed in 2 ways: using time blocks of 0.5 (solid lines) and 0.125 s (dotted lines). FIG.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2360
RESPIRATORY A
IMPEDANCE
0.51
0.1:
0.2
0.2
0.4
0.4
0.6
0.6
0.8
0.8
1.0
LO
1.2
1.2
i (I ’ s-l) FIG. 6. Cycle-per-cycle values of mean level of Rrs and Xrs in a healthy adult (A) and a patient with COPD (B) as a function of absolute values of respiratory flow at two times during the breathing cycles. l , Maximal inspiratory flow; 0, maximal expiratory flow.
DURING
BREATHING
way shunt in parallel with Zrs (13). This shunt also explains the negative frequency dependence of Rrs observed in healthy adults at times 4 and 5. We were surprised to observe a negative frequency dependence of Rrs and a shift to the right of the Xrs frequency curves with increased resonant frequency in patients with upper airway obstruction and also when the upper airway shunt was dealt with by means of the head generator technique. A negative frequency dependence of Rrs and increase in resonant frequency was observed in all patients of this group, particularly at times 2,4, and 5, i.e., in the course of inspiration and expiration. The TABLE 1. Individual and common regression coefficients (P s 0.05) of mean level and slope of instuntuneous respiratory resistance and reactance vs. corresponding flow at times 2 and 4 of the respiratory cycle in healthy subjects and patients with COPD and upper airway obstruction v,
R’“‘,
ml/s
x10
Rrd’), x1o-4
Xrs,
X1O-4
Xrdl’, x1o-4
Time2
Healthy subjects
maximal expiratory flow or halfway throughout the expiration1 and, in upper airway obstruction, at maximal inspiratory flow than at times of minimal flow (times 1 and 3) points to a flow dependence of the values of Rrs and Xrs. A volume dependence is not marked. Rrs or Xrs do not differ significantly when the transitions from inspiration to expiration &me 3) or from expiration to inspiration (time I) are compared. Still, Rrs tends to be less at time 3 than at time 1. The influence of respiratory flow on the values of Rrs and Xrs is substantiated by the study of the relationship between the spontaneous fluctuations of flow and the corresponding values of Rrs and Xrs at two moments in the breathing cycle (times 2 and 4). Mean levels of Rrs and Xrs increase and decrease, respectively, at larger flows in healthy subjects and patients with COPD. Simultaneously, the slope of the Xrs frequency curve tends to decrease. However, all variations of Rrs and Xrs cannot be reduced to an effect of airflow. Except in the group of upper airway obstruction, Rrs values are on the average higher and Xrs values less during expiration (time 4) than at a similar moment during inspiration (time 2; Figs. l--3), despite the fact that maximal flows are generally less during expiration than during inspiration (Table 1). This is illustrated in Fig. 6 for separate measurements from consecutive breathing cycles and confirms the conclusion of others (4,6,17,18) that, besides the amplitude of flow, the phase of the breathing cycle influences the values of Rrs (and Xrs). With respect to the head generator, the conventional technique yields similar variations of Rrs and Xrs during breathing. However, the variations are less pronounced. This smoothing effect, especially marked in upper airway obstruction, is because of the influence of the upper air’ A decrease of the values of Xrs during expiration results in an apparent decrease of inertance, calculated from the Xrs frequency curve assuming a one-alveolar model. This might explain the findings of Miller and Pimmel (14).
1 2 3 4 5
-0.339”
755-t-113
6541-49 718t163 5861~54 781+105
Common
-0.304
3.249+
0.095t
0.829
0.559* -1.029* -0.036* -0.488t -0.425
COPDpatients 933+97 924k-45
6 7 8
885_+50
9
1,011+80
6.403t
Common Upper airway patients 10 11 12
556+26 564+37 63Ok26
-1.862t
-8.923 -9.415 Time
2 3 4 5
-3.430 -1.328t
3.0897 -2.085*
Common Healthy subjects 1
-1.748.t -0.210*
-2.517.f
4
-723kll.9 -511+53
-479t98 -488~180 -580288
Common
0.204
-4.839t -2.397*
0.101*
-1.156”
1.320? 0.814-f
0.096
0.265
0.080
COPD patients 6 7 8
9
-943t114 -441+29
11 12
1.962* -0.594 2.390
-1.016
-606-t22 -716t30
Common Upper airway patients 10
1.753
5.255 -556t42 -403t53 -564t38
-14.742
Values are means t SD. Common, values of the common fegression line of the -group (given only when statistically significant), V, respiratory flow; Rrs, XPS, level of respiratory system resistance and reactance, respectively; Rrs (l) , Xr#), slope of respiratory system resistance and reactance, respectively. * P < 0.01; t P < 0.001.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
MG5YlfCA'l'UK.
Y llVlk’~UAN
L;r;
A
U UMN
ti
l5fCEA’l’HlN
ti
Z;Jbl
B 1.5 R.V.
0
33 yrs
1.0
.5
.O 8
16
24
32 Hz
8
16
24
32
Hz
16
24
32 Hz
-. 5
t
1
1
8
16
24
I
32 Hz
8
7. Rrs and Xrs values vs. frequency obtained with head generator in a healthy and during simulated upper airway obstruction (B) (see text). Numbers 1-5 correspond cycle.
adult during quiet breathing (A) to 5 moments within breathing
FIG.
average curves of Rrs and Xrs, obtained over a period of 32 s, i.e., over several breathing cycles, also demonstrated this phenomenon. We do not think that this is the result of an artifact or attributable to lower airway disease; none of these patients had a history of COPD. In addition, the phenomenon can be reproduced by asking healthy subjects to narrow voluntarily the glottis during breathing. In two of four subjects, this maneuver resulted in the appearance of a marked negative frequency dependence of Rrs mainly at times 2 and 4 and in a simultaneous shift to the right of the Xrs frequency curves (Fig. 7). In one subject, resistance simply increased without becoming frequency dependent, and in the other subject breathing became totally irregular. This suggests that 1) the findings in patients with upper airway obstruction are caused, indeed, by a narrowing of the upper airway; and 2) the increase of Rrs, the negative frequency dependence of Rrs, and the shift of the resonant frequency at times 2,4, and 5 in these subjects are a consequence of the influence of airflow on the values of Rrs and Xrs and are thus comparable to the flow-dependent changes in Rrs and Xrs observed in patients with COPD. In people with upper airway obstruction the effect of flow is more pronounced during inspiration; it is more prevailing during expiration in patients with COPD. The influence of a steady flow on the oscillatory impedance of the larynx has been studied on excised human larynx preparations by Jiang et al. (10). Superposition of
a steady flow on the forced oscillations, generated to determine the impedance of the larynx, results in an increase of resistance, a change of its frequency dependence (from positive to absent or even slightly negative), and a decrease of reactance mainly at higher frequencies. Although the mechanisms of the influence of steady flow on oscillatory resistance are not fully elucidated (5), the study on the excised larynx reproduces qualitatively the variations of Rrs and Xrs observed in the present study. Finally, one might wonder to what extent the changes of Rrs and Xrs observed during breathing are influenced by the fact that the computed values are not truly instantaneous but are sampled over a period of 0.5 s. This was investigated by reducing the sampling time to 0.125 s. Figure 5 shows that, as expected, a longer sampling period only reduces the actual variations of Rrs. This work was supported by a grant of the Fonds voor Geneeskundig Wetenschappelijk Onderzoek. Address for reprint requests: K. P. Van de Woestijne, Laboratorium voor Pneumologie, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Received
8 May
1991; accepted
in final
form
13 July
1992.
REFERENCES 1.
BAIER, H., A. WANNER, S.~ARZECKI,AND M. A. SACKNER. Relationships resistance
among glottis opening, respiratory flow and upper airway in humans. J. Appl. Physiol. 43: 603-611, 1977. 2. BRANCATISANO, T.,P.W. COLLETT,AND L.A. ENGEL. Respiratory
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
2362
3, 4.
5.
6. 7. 8.
9.
10.
RESPIRATORY
IMPEDANCE
movements of the vocal cords. J. Appl. Physiol. 54: 1269-1276, 1983. CAUBERGHS, M., AND K. P. VAN DE W~ESTIJNE. Effect of upper airway shunt and series properties on respiratory impedance measurements. J. Appl. Physiol. 66: 2274-2279, 1989. DAVIDSON, R. N., C. A. GREIG, A. HUSSAIN, AND K. B. SAUNDERS. Within-breath changes of airway calibre in patients with airflow obstruction by continuous measurement of respiratory impedance. Br. J. Dis. Chest 80: 335-352, 1986, DORKIN, H. L., A. C. JACKSON, D. J. STRIEDER, AND S. V. DAWSON. Interaction of oscillatory and unidirectional flows in straight tubes and an airway cast. J. Appl. Physiol. 52: 1097-1105, 1982. ENGLAND, S. J., D. BARTLETT, JR., AND J. A. DAUBENSPECK. Influence of human vocal cord movements on airflow and resistance during eupnea. J. Appl. Physiol. 52: 773-779, 1982. FOUKE, J. M., A. D. WOLIN, K, P. STROHL, AND G. M. GALBRAITH. EIastic characteristics of the airway wall. J. Appl. Physiol. 66: 962967,1989* FRANKEN, H., J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Systematic and random errors in the determination of respiratory impedance by means of the forced oscillation technique: a theoretical study. IEEE Trans. Biomed. Eng. 30: 642-651,1983. HOROWITZ, J. G., S. D. SIEGEL, F. P. PRIMIANO, JR., AND E. H. CHESTER. Computation of respiratory impedance from forced sinusoidal oscillations during breathing. Comput. Biomed. Res. 16: 499521, 1983. JIANG, T. X., M. CAUBERGHS, AND K. P. VAN DE WOESTIJNE. Resistance and reactance of the excised human larynx, trachea and main bronchi. J. Apple. Physiol. 63: 17881795, 1987.
DURING
BREATHING
11. LANDSER, F, J., J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Normal values of total respiratory resistance and reactance determined by forced oscillations. Influence of smoking. Chest 81: 586591,1982. 12. LANDSER, F. J., J. NAGELS, M. DEMEDTS, L. BILLIET, AND K. P. VAN DE WOESTIJNE. A new method to determine frequency characteristics of the respiratory system. J. Appl. Physiol. 41: 101-106, 1976. 13. MICHAELSON, E. D., E. D. GRASSMAN, AND W. R. PETERS. Pulmonary mechanics by spectral analysis of forced random noise. J. Clin. Inuest. 56: 1210-1230, 1975. 14. MILLER, T. K,, AND R. L. PIMMEL. Forced noise mechanical parameters during inspiration and expiration. J. Appl. Physiol. 52: l53O1534, 1982. 15. PESLIN, R., C. DUVIVIER, J. DIDELON, AND C. GALLINA. Respiratory impedance measured with head generator to minimize upper airway shunt. J. Appl. Physiol. 59: 1790-1795, 1985. 16. PESLIN, R., T, HIXON, AND J. MEAD. Variations des resistances thoraco-pulmonaires au tours du cycle ventilatoire htudiees par methode d’oscillation. Bull. Physio-Path. Respir. 7: 173-186, 1971. 17. PESLIN, R., Y. YING, C. GALLINA, AND C. D~TVIVIER. Within-breath variations of forced oscillation resistance in healthy subjects. Eur. Respir. J. 5: 86-92, 1992. 18. SEKISAWA, K., H. SASAKI, AND T. TAKISHIMA. Laryngeal resistance immediately after panting in control and constricted airways. J. Appl. Physiol. 58: 1164-1169, 1985. 19. STANESCU, D. C., J. PATTIJN, J. CLEMENT, AND K. P. VAN DE WOESTIJNE. Glottis opening and airway resistance. J. Appl. Physiol. 32: 460-466, 1972.
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.237.165.040) on December 6, 2018. Copyright © 1992 the American Physiological Society. All rights reserved.
