EFFECT OF BRONCHODILATION ON EXPIRATORY FLOW-LIMITATION AND
RESTING LUNG MECHANICS IN COPD
Online Data Supplement
Raffaele L. Dellacà1, Pasquale P. Pompilio1, Paul P. Walker2, Nick Duffy2, Antonio Pedotti1 and Peter M. A.
Calverley2
1
TBM Lab, Dipartimento di Bioingegneria, Politecnico di Milano University, Milano, Italy
2
University Hospital Aintree, University Department of Medicine, Liverpool, UK;
Sources of support: This work was partially supported by the British Lung Foundation. Raffaele Dellaca’ has
been the recipient of a European Respiratory Society Fellowship (Number 43).
Correspondence: Raffaele L. Dellaca’
Dipartimento di Bioingegneria
Politecnico di Milano
Piazza Leonardo da Vinci 32
I-20133 Milano Italy
Tel: +39 02 2399 9005
Fax: +39 02 2399 9000
E-Mail: raffaele.dellaca@polimi.it
Running head: Bronchodilation and flow-limitation in COPD
Comparison between single frequency and multifrequency forcing
We have used the forced oscillation method to identify the presence of expiratory flow limitation on a
breath by breath basis and to extend our observations to consider the effect of bronchodilators on the
heterogeneity of lung obstruction in COPD by using a within-breath multifrquency PRN method.
The measurements of Zin by FOT is usually carried on by either multifrequency signals or single
sinusoidal signals. The first approach is usually applied by recording data for several breaths and by estimating
the average mechanical response of the respiratory system at several frequencies(1). Conversely, single
frequency signals have been used for estimating the within-breath variation of Zin(2;3). These two approaches
provide complementary information: multifrequency signals allow the evaluation of the heterogeneity of the
obstruction by providing the frequency dependence of Rrs and Xrs(4;5), while the single frequency signal
provides information on the presence and degree of EFL (6).
In principle, however, the two approaches are not mutually exclusive and, therefore, we developed and
validated an approach for measuring within-breath multifrequency Zin. In order to provide a good signal-tonoise ratio we limited the number of frequencies of our forcing signal to three and we choose these frequencies
to reduce the effects of non-linearities.
To our knowledge there are no studies reporting the use of multifrequency signals for the estimation of
within-breath Zin in humans.
To validate the use of multifrequency forcing signal in detecting EFL we compared the values of Xrs
at baseline measured by using the single sinusoidal forcing with the ones computed from the 5Hz component of
the multyfrequency signal. On average, the difference between single frequency and multifrequency was
0.14±1.31 cmH2O*s/L, suggesting the absence of a systematic difference (bias) in the Xrs computed by the
two different forcing waveforms. The average of the absolute value of the difference between the two
measurements, which represent the average ‘distance’ between the measurements, was 0.84±1.00 cmH2O*s/L.
The linear regression analysis provided a slope of 0.93 and as r² of 0.92 (Figure E1). All these results suggest a
substantial agreement between the two measurements.
On 42 patients, only 5 would be classified as FL or NFL differently by the Xrs computed by the two
waveforms (3 would be FL with the single frequency forcing and NFL by the PRN). In 4 of these 5 patients we
found that there were breaths classified differently (i.e. some FL and some NFL) in the same recording,
suggesting that these patients were changing breath-by-breath their condition between FL and NFL for
physiological rather than methodological reasons and, therefore, were borderline between FL and NFL.
Considering that the measurements were not simultaneous and that there is a natural variability in
patient’s condition, as we previously observed(7), these results confirm that the single frequency and the multifrequency within-breath methods provide substantially the same results, as theoretically expected.
Concerning the other Zin parameters at 5Hz, we found that the use of our within-breath multi-frequency
analysis produced very comparable results to that obtained when patients were tested with a single sinusoidal
waveform (Table E1). For this reason, all the results reported in our study considered the data measured with
the multifrequency signal only.
We found only a slightly grater difference for both Zin parameters measured during expiration and the
ones measured throughout all the breathing cycle when only EFL patients were considered (Table E1), in
agreement with the hypothesis that the high nonlinearity of flow-limitation may affect the measurement of Zin.
References
(1) Michaelson ED, Grassman ED, Peters WR. Pulmonary mechanics by spectral analysis of forced random
noise. J Clin Invest 1975 Nov;56(5):1210-30.
(2) Horowitz JG, Siegel SD, Primiano FP, Jr., Chester EH. Computation of respiratory impedance from
forced sinusoidal oscillations during breathing. Comput Biomed Res 1983 Dec;16(6):499-521.
(3) Peslin R, Ying Y, Gallina C, Duvivier C. Within-breath variations of forced oscillation resistance in
healthy subjects. Eur Respir J 1992;5(1):86-92.
(4) Lutchen KR, Greenstein JL, Suki B. How inhomogeneities and airway walls affect frequency dependence
and separation of airway and tissue properties. J Appl Physiol 1996;80(5):1696-707.
(5) Otis AB, Mc Kerrow CB, Bartlett RA, Mead J, McIlroy MB, Selverstone NJ, et al. Mechanical factors in
distribution of pulmonary ventilation. J Appl Physiol 1956;8:427-43.
(6) Dellaca RL, Santus P, Aliverti A, Stevenson N, Centanni S, Macklem PT, et al. Detection of expiratory
flow limitation in COPD using the forced oscillation technique. Eur Respir J 2004 Feb;23(2):232-40.
(7) Dellaca RL, Duffy N, Pompilio PP, Aliverti A, Koulouris NG, Pedotti A, et al. Expiratory flow limitation
detected by forced oscillation and negative expiratory pressure. Eur Respir J 2007 Feb;29(2):363-74.
Table E1: Comparison between impedance indices computed during the application of single frequency (sf)
and multifrequency (mf) forcing signals.
sf
Mean
All subjects
mf
STD
Mean
mf-sf
STD
p
Mean
STD
abs(mf-sf)
Mean
STD
Xinsp
-2.293 ± 1.234
-2.330 ± 1.162
0.693
-0.037 ± 0.603
0.439 ± 0.410
Xexp
-5.347 ± 4.273
-5.273 ± 4.275
0.757
0.074 ± 1.548
1.022 ± 1.153
Xtot
Xrs
-4.279 ± 3.274
-4.264 ± 3.281
0.933
0.015 ± 1.124
0.734 ± 0.843
3.054 ± 3.513
2.943 ± 3.411
0.586
-0.111 ± 1.316
0.837 ± 1.013
Rinsp
5.173 ± 1.772
5.054 ± 1.645
0.287
-0.119 ± 0.713
0.532 ± 0.482
Rexp
6.719 ± 3.128
6.181 ± 2.461
0.003
-0.538 ± 1.094
0.977 ± 0.718
Rtot
6.146 ± 2.606
5.774 ± 2.120
0.011
-0.372 ± 0.902
0.780 ± 0.577
Xinsp
-1.679 ± 0.968
-1.663 ± 0.914
0.884
0.016 ± 0.505
0.352 ± 0.353
Xexp
-2.469 ± 1.963
-2.085 ± 1.449
0.046
0.384 ± 0.851
0.684 ± 0.623
Xtot
Xrs
-2.151 ± 1.558
-1.914 ± 1.220
0.116
0.238 ± 0.680
0.516 ± 0.492
0.790 ± 1.189
0.422 ± 0.730
0.008
-0.368 ± 0.588
0.465 ± 0.511
Rinsp
4.479 ± 1.419
4.394 ± 1.242
0.512
-0.086 ± 0.603
0.425 ± 0.427
Rexp
5.747 ± 1.970
5.435 ± 1.533
0.125
-0.311 ± 0.915
0.809 ± 0.504
Rtot
5.213 ± 1.705
5.013 ± 1.377
0.224
-0.200 ± 0.749
0.624 ± 0.441
Xinsp
-2.969 ± 1.155
-3.064 ± 0.953
0.553
-0.095 ± 0.704
0.534 ± 0.454
Xexp
-8.513 ± 3.872
-8.779 ± 3.522
0.565
-0.266 ± 2.033
1.395 ± 1.470
Xtot
Xrs
-6.619 ± 3.072
-6.849 ± 2.855
0.485
-0.231 ± 1.446
0.974 ± 1.072
5.545 ± 3.551
5.716 ± 3.010
0.674
0.171 ± 1.787
1.247 ± 1.260
Rinsp
5.935 ± 1.839
5.781 ± 1.754
0.416
-0.155 ± 0.832
0.650 ± 0.522
Rexp
7.788 ± 3.811
7.002 ± 3.020
0.010
-0.786 ± 1.238
1.162 ± 0.874
Rtot
7.172 ± 3.053
6.610 ± 2.489
0.025
-0.562 ± 1.031
0.951 ± 0.666
Non Flow-Limited
Flow Limited
Table E2: Breathing pattern and within-breath input impedance measured at 5, 11 and 19Hz data for patients
before (Pre) and after (Post) bronchodilation (BD). Impedance data are expressed as cmH2O*s/L.
11 Hz
19 Hz
Post BD
Mean ± SD
11.04 ± 3.46
12.05 ± 3.73
< 0.001
p
Ve
L/min
Vt
L
0.66 ± 0.24
0.71 ± 0.24
0.014
RR
B/min
18.1 ± 5.6
18.1 ± 5.4
0.936
Ti
s
1.37 ± 0.47
1.37 ± 0.54
0.975
Tot
s
3.75 ± 1.53
3.74 ± 1.63
0.968
0.38 ± 0.06
0.37 ± 0.05
0.723
Ti/Ttot
5 Hz
Pre BD
Mean ± SD
Vt/Ti
L/s
0.50 ± 0.17
0.54 ± 0.17
< 0.001
Vt/Te
L/s
0.30 ± 0.09
0.33 ± 0.11
0.001
Rinsp
5.1 ± 1.6
4.2 ± 1.5
< 0.001
Rexp
6.2 ± 2.5
5.8 ± 2.7
0.036
Rtot
5.8 ± 2.1
5.2 ± 2.2
0.001
Xinsp
-2.3 ± 1.2
-1.8 ± 1.1
< 0.001
Xexp
-5.3 ± 4.3
-3.8 ± 3.3
0.001
Xtot
-4.3 ± 3.3
-3.1 ± 2.5
0.001
Xrs
2.9 ± 3.4
2.0 ± 2.5
0.004
R5  R19
1.8 ± 1.0
1.2 ± 0.9
< 0.001
Rinsp
4.0 ± 1.3
3.5 ± 1.1
< 0.001
Rexp
4.5 ± 1.6
4.4 ± 1.5
0.385
Rtot
4.3 ± 1.4
4.1 ± 1.3
0.025
Xinsp
-1.5 ± 1.0
-1.0 ± 0.9
< 0.001
Xexp
-3.0 ± 2.2
-2.2 ± 1.8
< 0.001
Xtot
-2.5 ± 1.8
-1.8 ± 1.5
< 0.001
Rinsp
3.2 ± 1.0
3.0 ± 0.9
0.002
Rexp
3.7 ± 1.2
3.6 ± 1.2
0.429
Rtot
3.5 ± 1.1
3.4 ± 1.1
0.085
Xinsp
-0.5 ± 0.7
0.0 ± 0.6
< 0.001
Xexp
-1.3 ± 1.1
-0.8 ± 1.0
< 0.001
Xtot
-1.0 ± 1.0
-0.5 ± 0.9
< 0.001
Table E3: Lung function, breathing pattern and impedance data at 5, 11 and 19Hz for patients who were not
flow-limited at baseline (NFL) and patients who were (FL). For each group, data are reported before (Pre) and
after (Post) bronchodilation (BD). The p values are reported for the paired comparison pre and post BD in each
group and for the unpaired comparison between NFL and FL at baseline (NFL vs. FL column). Impedance data
are expressed as cmH2O*s/L.
Non flow-limited at baseline
Pre BD
Post BD
Mean ± SD
Mean ± SD
FEV1
FEV1/FVC
FVC
SVC
p
p
1.47 ± 0.53
< 0.001
0.95 ± 0.27
1.14 ± 0.30
< 0.001
0.007
%pred
47.89 ± 14.55
54.72 ± 17.34
< 0.001
36.10 ± 10.07
43.15 ± 11.89
< 0.001
0.004
%
50.27 ± 10.59
50.36 ± 11.52
0.504
43.00 ± 9.81
41.90 ± 10.24
0.380
0.027
(L)
2.54 ± 0.70
2.91 ± 0.77
< 0.001
2.28 ± 0.65
2.80 ± 0.77
< 0.001
0.213
73.22 ± 14.64
83.26 ± 13.86
< 0.001
63.70 ± 12.32
78.60 ± 16.38
< 0.001
0.029
2.61 ± 0.72
2.90 ± 0.83
< 0.001
2.59 ± 0.70
2.99 ± 0.84
< 0.001
0.943
74.47 ± 13.56
82.77 ± 16.16
< 0.001
71.40 ± 11.68
82.80 ± 16.94
< 0.001
0.439
1.85 ± 0.53
2.01 ± 0.66
< 0.001
1.86 ± 0.53
2.18 ± 0.59
< 0.001
0.969
75.72 ± 18.47
81.04 ± 19.28
< 0.001
69.90 ± 17.28
82.00 ± 19.02
< 0.001
0.299
4.29 ± 1.21
4.02 ± 0.98
< 0.001
5.40 ± 1.18
5.04 ± 1.10
0.020
0.004
216.81 ± 57.88
203.69 ± 46.28
< 0.001
255.00 ± 54.92
238.11 ± 50.72
0.015
0.035
5.16 ± 1.33
4.93 ± 1.24
< 0.001
6.14 ± 1.49
5.84 ± 1.39
0.019
0.030
172.53 ± 33.05
164.73 ± 31.44
< 0.001
197.65 ± 35.64
188.28 ± 33.75
0.019
0.023
%pred
(L)
%pred
(L)
IC
%pred
(L)
RV
%pred
TGV
(L)
%pred
(L)
TLC
%pred
IC/TLC%
19
Hz
6.97 ± 1.61
0.261
7.99 ± 1.67
7.97 ± 1.57
0.747
0.070
124.48 ± 17.33
0.184
138.65 ± 18.38
137.94 ± 15.73
0.703
0.031
26.7 ± 5.9
29.3 ± 7.1
0.001
24.5 ± 6.9
29.2 ± 7.5
< 0.001
0.284
L/min
9.94 ± 2.96
11.26 ± 3.21
< 0.001
12.24 ± 3.65
12.93 ± 4.14
0.112
0.030
Vt
L
0.58 ± 0.24
0.64 ± 0.22
0.088
0.74 ± 0.21
0.79 ± 0.26
0.080
0.038
RR
B/min
18.6 ± 6.5
18.8 ± 6.2
0.775
17.4 ± 4.6
17.3 ± 4.4
0.847
0.496
Ti
s
1.45 ± 0.56
1.47 ± 0.66
0.881
1.29 ± 0.34
1.27 ± 0.37
0.673
0.273
Tot
s
3.76 ± 1.85
3.77 ± 2.09
0.962
3.74 ± 1.11
3.72 ± 0.96
0.895
0.968
0.40 ± 0.05
0.40 ± 0.04
0.684
0.35 ± 0.05
0.35 ± 0.06
0.269
0.010
Vt/Ti
L/s
0.42 ± 0.13
0.47 ± 0.12
0.010
0.59 ± 0.17
0.63 ± 0.17
0.005
0.001
Vt/Te
L/s
0.28 ± 0.09
0.32 ± 0.10
< 0.001
0.32 ± 0.10
0.34 ± 0.12
0.239
0.157
Rinsp
4.4 ± 1.2
3.8 ± 1.5
0.014
5.8 ± 1.8
4.6 ± 1.3
< 0.001
0.005
Rexp
5.4 ± 1.5
4.9 ± 1.6
0.032
7.0 ± 3.0
6.9 ± 3.3
0.511
0.038
Rtot
5.0 ± 1.4
4.5 ± 1.5
0.024
6.6 ± 2.5
6.1 ± 2.6
0.020
0.013
Xinsp
-1.7 ± 0.9
-1.5 ± 1.1
0.318
-3.1 ± 1.0
-2.2 ± 1.1
< 0.001
< 0.001
Xexp
-2.1 ± 1.4
-2.0 ± 1.7
0.601
-8.8 ± 3.5
-5.8 ± 3.4
< 0.001
< 0.001
Xtot
Xrs
-1.9 ± 1.2
-1.8 ± 1.5
0.527
-6.8 ± 2.9
-4.6 ± 2.6
< 0.001
< 0.001
0.4 ± 0.7
0.4 ± 0.8
0.860
5.7 ± 3.0
3.7 ± 2.7
0.002
< 0.001
R5  R19
1.2 ± 0.7
0.8 ± 0.9
0.019
2.5 ± 0.7
1.6 ± 0.6
< 0.001
< 0.001
0.026
4.3 ± 1.6
3.6 ± 1.1
< 0.001
0.207
4.2 ± 1.1
0.063
4.5 ± 2.0
4.6 ± 1.9
0.281
0.978
Rtot
4.2 ± 1.1
3.8 ± 1.1
0.042
4.4 ± 1.8
4.3 ± 1.6
0.336
0.606
Xinsp
-1.0 ± 0.7
-0.6 ± 1.0
0.048
-2.2 ± 0.8
-1.3 ± 0.7
< 0.001
< 0.001
Xexp
-1.5 ± 0.9
-1.2 ± 1.1
0.105
-4.7 ± 1.9
-3.3 ± 1.8
< 0.001
< 0.001
Xtot
-1.3 ± 0.8
-1.0 ± 1.1
0.085
-3.9 ± 1.5
-2.7 ± 1.4
< 0.001
< 0.001
Rinsp
3.2 ± 0.8
3.0 ± 0.9
0.085
3.3 ± 1.2
3.0 ± 1.0
0.006
0.852
Rexp
3.7 ± 0.9
3.6 ± 0.8
0.189
3.6 ± 1.4
3.7 ± 1.5
0.798
0.850
Rtot
3.5 ± 0.8
3.3 ± 0.8
0.121
3.5 ± 1.3
3.4 ± 1.3
0.440
0.998
s
3.4 ± 1.1
4.5 ± 1.2
r
3.8 ± 1.0
X
Rinsp
Rexp

11 Hz
7.02 ± 1.66
125.46 ± 19.76
Ve
Ti/Ttot
5 Hz
NFL vs. FL
1.27 ± 0.43
(L)
p
Flow-limited at baseline
Pre BD
Post BD
Mean ± SD
Mean ± SD
Xinsp
-0.2 ± 0.5
0.2 ± 0.6
0.007
-0.9 ± 0.6
-0.3 ± 0.4
< 0.001
< 0.001
Xexp
-0.6 ± 0.6
-0.3 ± 0.8
0.024
-2.0 ± 1.1
-1.3 ± 1.0
< 0.001
< 0.001
Xtot
-0.4 ± 0.6
-0.1 ± 0.7
0.015
-1.6 ± 1.0
-1.0 ± 0.8
< 0.001
< 0.001
Table E4: Spirometric data, lung volumes, breathing pattern and Zrs data for responder and non responder
patients to brocnhodilation. The p values are reported for the paired comparison pre and post BD in each group
and for the unpaired comparison between non responders (NR) and responders (R) (NR vs. R column).
Pre BD
Mean ± SD
FEV1
FEV1/FVC
FVC
SVC
(L)
%pred
Hz
1.20 ± 0.39
1.55 ± 0.45
<0.001
NS
43.51 ± 11.80
56.23 ± 13.83
<0.001
NS
NS
0.47 ± 0.09
0.48 ± 0.11
NS
NS
(L)
2.32 ± 0.68
2.60 ± 0.12
<0.001
2.56 ± 0.69
3.29 ± 0.69
<0.001
NS
67.70 ± 16.45
74.88 ± 14.55
<0.001
70.07 ± 11.49
91.80 ± 13.74
<0.001
NS
2.59 ± 0.78
2.71 ± 0.77
NS
2.72 ± 0.68
3.31 ± 0.89
<0.001
NS
74.52 ± 14.14
77.76 ± 13.98
0.050
73.38 ± 12.80
89.17 ± 18.83
<0.001
NS
1.80 ± 0.51
1.97 ± 0.56
0.001
1.94 ± 0.57
2.26 ± 0.66
<0.001
NS
72.17 ± 16.87
79.52 ± 17.46
0.080
74.40 ± 20.22
84.95 ± 19.58
<0.001
NS
4.52 ± 1.35
4.45 ± 1.14
NS
4.76 ± 1.13
4.06 ± 0.92
<0.001
NS
223.74 ± 60.60
222.17 ± 47.55
NS
228.23 ± 54.49
189.48 ± 44.44
<0.001
NS
5.31 ± 1.61
5.10 ± 1.37
0.042
5.59 ± 1.18
5.11 ± 0.92
<0.001
NS
179.41 ± 39.17
171.86 ± 31.37
0.027
178.60 ± 30.12
162.85 ± 32.70
<0.001
NS
7.09 ± 1.82
7.10 ± 1.66
NS
7.52 ± 1.42
7.34 ± 1.37
NS
NS
129.84 ± 18.12
129.07 ± 13.12
NS
127.60 ± 20.40
124.97 ± 19.41
0.086
NS
25.4 ± 6.6
28.1 ± 6.8
0.001
26.0 ± 6.2
30.7 ± 7.6
<0.001
NS
10.10 ± 3.32
10.91 ± 3.13
0.021
12.28 ± 3.34
13.58 ± 4.00
0.005
NS
%pred
(L)
%pred
(L)
%pred
(L)
%pred
Ve
L/min
Vt
L
0.64 ± 0.24
0.71 ± 0.27
0.037
0.67 ± 0.24
0.71 ± 0.22
NS
NS
RR
B/min
16.9 ± 5.3
16.7 ± 5.1
NS
19.6 ± 5.7
20.0 ± 5.4
NS
NS
Ti
s
1.40 ± 0.44
1.47 ± 0.65
NS
1.34 ± 0.53
1.24 ± 0.31
NS
NS
Tot
s
4.03 ± 1.76
4.12 ± 1.97
NS
3.37 ± 1.08
3.24 ± 0.85
NS
NS
0.36 ± 0.06
0.36 ± 0.06
NS
0.39 ± 0.05
0.39 ± 0.04
NS
NS
Vt/Ti
L/s
0.48 ± 0.16
0.51 ± 0.15
0.006
0.53 ± 0.18
0.59 ± 0.19
0.009
NS
Vt/Te
L/s
0.27 ± 0.09
0.29 ± 0.09
0.037
0.34 ± 0.08
0.38 ± 0.11
0.013
NS
Rinsp
4.9 ± 1.8
4.4 ± 1.5
0.007
5.3 ± 1.5
3.9 ± 1.3
<0.001
NS
Rexp
6.4 ± 3.2
6.4 ± 3.3
NS
5.9 ± 1.0
5.1 ± 1.4
0.007
NS
Rtot
5.8 ± 2.7
5.7 ± 2.7
NS
5.7 ± 1.1
4.7 ± 1.3
0.001
NS
Xinsp
-2.2 ± 1.2
-1.9 ± 1.1
NS
-2.5 ± 1.1
-1.7 ± 1.2
<0.001
NS
Xexp
-5.3 ± 4.9
-4.3 ± 3.8
NS
-5.2 ± 3.3
-3.1 ± 2.4
<0.001
NS
Xtot
Xrs
-4.3 ± 3.8
-3.5 ± 2.8
NS
-4.2 ± 2.4
-2.6 ± 1.9
<0.001
NS
3.1 ± 4.0
2.4 ± 3.0
NS
2.7 ± 2.6
1.4 ± 1.5
0.001
NS
R5  R19
1.6 ± 0.9
1.2 ± 0.8
0.011
2.1 ± 1.0
1.1 ± 1.0
<0.001
NS
NS
4.0 ± 0.9
3.2 ± 0.7
<0.001
NS
4.7 ± 1.9
NS
4.2 ± 0.8
4.0 ± 0.8
NS
NS
Rtot
4.4 ± 1.8
4.4 ± 1.6
NS
4.1 ± 0.7
3.7 ± 0.7
0.014
NS
Xinsp
-1.3 ± 0.9
-1.0 ± 0.8
0.013
-2.5 ± 1.1
-0.9 ± 1.0
<0.001
NS
Xexp
-3.0 ± 2.5
-2.5 ± 1.7
NS
-5.2 ± 3.3
-1.8 ± 1.4
<0.001
NS
Xtot
-2.5 ± 2.1
-2.0 ± 1.7
0.047
-4.2 ± 2.4
-1.5 ± 1.2
<0.001
NS
Rinsp
3.3 ± 1.2
3.2 ± 1.1
NS
3.2 ± 0.7
2.7 ± 0.5
<0.001
NS
Rexp
3.8 ± 1.4
3.8 ± 1.4
NS
3.5 ± 0.6
3.3 ± 0.6
NS
NS
Rtot
3.6 ± 1.3
3.6 ± 1.3
NS
3.4 ± 0.5
3.1 ± 0.5
0.031
NS
Xinsp
-0.4 ± 0.7
-0.1 ± 0.6
0.004
-0.8 ± 0.6
0.0 ± 0.6
<0.001
NS
Xexp
-1.3 ± 1.4
-0.9 ± 1.1
0.039
-1.3 ± 0.8
-0.5 ± 0.8
<0.001
NS
Xtot
-1.0 ± 1.2
-0.7 ± 1.0
0.021
-1.1 ± 0.7
-0.3 ± 0.7
<0.001
NS
s
3.8 ± 1.2
4.7 ± 2.0
r
4.0 ± 1.5
X
Rinsp
Rexp

19
NS
<0.001
Ti/Ttot
11 Hz
p
1.15 ± 0.40
0.45 ± 0.12
IC/TLC%
5 Hz
p
1.06 ± 0.39
44.19 ± 15.92
%pred
TLC
NR vs. R
0.46 ± 0.11
(L)
TGV
Responders
Post BD
Mean ± SD
40.93 ± 15.15
%pred
RV
p
Pre BD
Mean ± SD
%
(L)
IC
Not responders
Post BD
Mean ± SD
Figure E1: Linear regression analysis of Xrs measured at 5Hz during single frequency (SF) and
multifrequency (MF) forcing.
16
14
Xrs MF (cmH2O*s/L)
12
10
8
6
4
2
0
-2
-2
0
2
4
6
8
10
Xrs SF (cmH2O*s/L)
12
14
16
18