Evaluation of Exertional Ventilatory Parameters Using Oscillometry in COPD

Figures & data

Table 1 Subjects’ Baseline Characteristics (n=55)

Age, Years, n	73.49 (5.56)	61–83
Sex, male/female	54/1
BMI, kg m^−2	20.9 (3.2)	14.7–25.8
Cigarette smoking, pack years	56.5 (26.5)	11–141
GOLD stage I/II/III/IV, n	6/10/29/10
GOLD category A/B/C/D, n	10/29/0/16
mMRC dyspnea scale 0/1/2/3/4, n	0/10/22/12/11
Medications
LAMA, n	53
LABA, n	43
ICS, n	22
Triple therapy, n	21
Spirometry
FEV1, L	1.24 (0.62)	0.41–3.73
% FEV1, % predicted	47.10 (22.96)	16.7–141.8
FVC, L	3.01 (0.89)	1.24–5.39
% FVC, % predicted	89.4 (23.7)	39.4–159.9
FEV1/FVC, %	40.35 (11.17)	21.2–69.2
VC, L	3.05 (0.81)	1.68–5.31
%VC, %	84.45 (19.73)	48.40–146.30
IC, L	1.92 (0.52)	0.92–3.08
IRV, L	0.96 (0.44)	0.19–1.79
ERV, L	1.13 (0.47)	0.33–2.85
VT, L	0.96 (0.32)	0.29–1.77

Note: Data are presented as the mean (SD) and the minimum and maximum values, unless otherwise stated.

Abbreviations: BMI, body mass index; ERV, expiratory reserve volume; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IC, inspiratory capacity; ICS, inhaled corticosteroids; IRV, inspiratory reserve volume; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; mMRC dyspnea scale, modified Medical Research Council dyspnea scale; SD, standard deviation; VC, vital capacity; V_T, tidal volume.

Table 2 Results of Baseline Respiratory Impedance at Rest (n=55)

R5, cmH2O/L/s
Inspiratory	3.62 (1.30)	1.20–6.96
Expiratory	4.88 (2.19)	1.53–13.83
Average	4.25 (1.64)	1.54–10.04
ΔR5	−1.26 (1.50)	−7.59–1.19
R20, cmH2O/L/s
Inspiratory	2.74 (0.80)	1.13–4.75
Expiratory	3.32 (1.28)	1.44–7.94
Average	3.03 (0.96)	1.49–6.08
ΔR20	−0.58 (0.91)	−3.76–0.77
R5-R20, cmH2O/L/s
Inspiratory	0.89 (0.60)	−0.07–2.80
Expiratory	1.56 (0.99)	0.01–5.89
Average	1.23 (0.74)	0.01–3.96
ΔR5-R20	−0.68 (0.71)	−3.86–0.52
X5, cmH2O/L/s
Inspiratory	−1.29 (0.85)	−3.55 - −0.16
Expiratory	−3.64 (3.12)	−12.56 - −0.08
Average	−2.47 (1.89)	−7.54 - −0.13
ΔX5	2.36 (2.58)	−0.16–10.05
Fres, Hz
Inspiratory	14.53 (5.81)	5.91–30.60
Expiratory	20.08 (7.81)	5.56–34.28
Average	17.31 (6.47)	5.74–32.18
ΔFres	−5.55 (4.65)	−18.51–1.04
ALX, cmH2O/L/s × Hz
Inspiratory	9.32 (9.12)	0.54–42.08
Expiratory	33.74 (33.57)	0.29–145.30
Average	21.53 (20.14)	0.46–83.41
ΔALX	−24.41 (28.24)	−123.78–0.92

Note: Data are presented as the mean (SD) and the minimum and maximum values, unless otherwise stated.

Abbreviations: ALX, low-frequency reactance area; Δ, difference between inspiratory and expiratory phases; Fres, resonant frequency; R5 and R20, respiratory system resistance at 5 and 20 Hz, respectively; SD, standard deviation; X5, respiratory system reactance at 5 Hz.

Table 3 Results of Baseline Respiratory Impedance at Rest in the Various GOLD Stages (Stages I–IV) (n=55)

Parameter	GOLD Stages I, II (n=16)		GOLD Stages III, IV (n=39)		p
R5, cmH2O/L/s
Inspiratory	2.70 (1.25)	1.20–6.24	4.00 (1.14)	1.96–6.96	**
Expiratory	4.26 (2.88)	1.53–13.83	5.14 (1.83)	2.24–11.82	*
Average	3.48 (2.03)	1.54–10.04	4.57 (1.36)	2.10–9.14	**
ΔR5	−1.56 (1.82)	−7.59–0.02	−1.13 (1.36)	−5.64–1.19	NS
R20, cmH2O/L/s
Inspiratory	2.18 (0.73)	1.13–4.21	2.97 (0.71)	1.71–4.75	**
Expiratory	3.01 (1.54)	1.44–7.94	3.45 (1.15)	1.78–7.36	NS
Average	2.59 (1.10)	1.49–6.08	3.21 (0.85)	1.75–5.94	**
ΔR20	−0.83 (0.97)	−0.37–0.18	−0.48 (0.88)	−3.76–0.77	NS
R5-R20, cmH2O/L/s
Inspiratory	0.52 (0.54)	−0.07–2.03	1.04 (0.56)	0.25–2.80	**
Expiratory	1.25 (1.38)	0.01–5.89	1.69 (0.77)	0.14–4.46	**
Average	0.89 (0.94)	0.01–3.96	1.04 (0.56)	0.29–3.20	**
ΔR5-R20	−0.73 (0.93)	−3.86–0.52	−0.65 (0.62)	−2.53–0.42	NS
X5, cmH2O/L/s
Inspiratory	−0.69 (0.53)	−2.19 - −0.16	−1.53 (0.84)	−3.55 - −0.19	**
Expiratory	−1.72 (2.85)	−11.11 - −0.08	−4.43 (2.90)	−12.56 - −0.42	**
Average	−1.20 (1.67)	−6.65 - −0.13	−2.98 (1.74)	−7.54 - −0.49	**
ΔX5	1.03 (2.39)	−0.15–8.92	2.90 (2.48)	−0.16–10.05	**
Fres, Hz
Inspiratory	9.87 (3.27)	5.91–17.08	16.44 (5.55)	6.58–30.60	**
Expiratory	12.71 (6.37)	5.56–28.20	23.10 (6.20)	10.67–34.28	**
Average	11.29 (4.71)	5.74–22.64	19.77 (5.42)	9.82–32.18	**
ΔFres	−2.84 (3.73)	−11.12–1.04	−6.65 (4.58)	−18.51–0.37	**
ALX, cmH2O/L/s × Hz
Inspiratory	3.30 (3.43)	0.54–13.25	11.79 (9.59)	0.60–42.08	**
Expiratory	13.41 (26.96)	0.29–97.59	42.07 (32.70)	2.04–145.30	**
Average	8.35 (15.09)	0.46–55.42	26.93 (19.58)	1.93–83.41	**
ΔALX	−10.11 (23.80)	−84.34–0.81	−30.28 (28.08)	−123.78–0.92	**

Notes: Data are presented as the mean (SD) and the minimum and maximum values, unless otherwise stated. *and **p<0.05 and p<0.01 by the Mann–Whitney U-test, respectively.

Abbreviations: ALX, low-frequency reactance area; Δ, difference between inspiratory and expiratory phases; Fres, resonant frequency; GOLD, Global Initiative For Chronic Obstructive Lung Disease; NS, not significant; R5 and R20, respiratory system resistance at 5 and 20 Hz, respectively; SD, standard deviation; X5, respiratory system reactance at 5 Hz.

Figure 1 Inspiratory impedance at rest in the various GOLD stages (stages I–IV) (n=55). (A) Respiratory resistance and GOLD stages at baseline. (B) Respiratory reactance and GOLD stages at baseline. Sixteen subjects were GOLD stage I or II and 39 subjects were GOLD stage III or IV. **p<0.01 by the Mann–Whitney U-test.

Abbreviations: ALX, low-frequency reactance area; Fres, resonant frequency; GOLD, Global Initiative for Chronic Obstructive Lung Disease; R5 and R20, respiratory system resistance at 5 and 20 Hz, respectively; X5, respiratory system reactance at 5 Hz.

Table 4 Results of Cardiopulmonary Exercise Testing at Peak Exercise and at Rest (n=55)

	At Peak Exercise		At Rest
Incremental load testing
VT ex, mL	1132 (332)	597–2047	696 (169)	354–1192
VT ex/Te, mL/sec	924 (363)	322–2043	370 (90)	175–660
fR, breaths/min	29 (5)	16–40	21 (6)	8–32
V’E, L/min	33.0 (10.6)	14.6–63.9	13.7 (2.5)	6.8–19.1
Ti/Ttot	0.38 (0.08)	0.24–0.68	0.37 (0.07)	0.22–0.62
V’O2, mL/min	711 (236)	313–1218	249 (45)	171–361
VD/VT	0.40 (0.05)	0.31–0.50	0.44 (0.04)	0.38–0.54
V’E/V’CO2	46.6 (7.6)	33.3–72.3	61.6 (8.6)	46.5–81.9

Note: Data are presented as the mean (SD) and the minimum and maximum values, unless otherwise stated.

Abbreviations: f_R, breathing frequency; SD, standard deviation; Te, expiration time; Ti/Ttot, inspiratory duty cycle; V_D, physiological dead space; V_D/V_T, dead space to tidal volume ratio; V’_E, minute ventilation; V’_E/V’_CO2, ventilatory equivalent for carbon dioxide; V’_O2, oxygen uptake; V_T, tidal volume; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow.

Table 5 Results of Cardiopulmonary Exercise Testing (CPET) at Rest and at Peak Exercise in Various GOLD Stages (Stages I–IV) (n=55)

	GOLD Stages I, II (n=16)				GOLD Stages III, IV (n=39)
	At peak exercise		At rest		At peak exercise		At rest
Incremental load testing
VT ex, mL	1515 (246)*	1137–2047	739 (145)	488–935	975 (214)	597–1445	679 (177)	354–1192
VT ex/Te, mL/sec	1297 (296)*	927–2043	383 (56)	292–467	771 (265)	322–1464	366 (102)	175–660
fR, breath/min	29 (5)	24–40	20 (4)	14–27	29 (5)	16–40	21 (6)	8–32
V’E, L/min	44.1 (8.3)*	33.0–63.9	14.1 (2.0)	10.4–17.6	28.5 (7.9)	14.6–48.3	13.6 (2.8)	6.8–19.1
Ti/Ttot	0.43 (0.06)*	0.35–0.60	0.38 (0.07)	0.30–0.62	0.36 (0.09)	0.24–0.68	0.36 (0.08)	0.22–0.62
V’O2, mL/min	928 (168)*	696–1218	270 (45)*	171–361	622 (201)	313–1214	240 (42)	173–327
VD/VT	0.35 (0.03)*	0.31–0.40	0.42 (0.04)*	0.38–0.49	0.42 (0.04)	0.34–0.50	0.45 (0.04)	0.38–0.54
V’E/V’CO2	44.9 (6.1)	36.0–54.4	59.5 (8.5)	46.5–78.3	47.2 (8.1)	37.0–72.3	62.5 (8.6)	46.6–81.9

Notes: Data are presented as the mean (SD) and the minimum and maximum values, unless otherwise stated. *p<0.05 by the Mann–Whitney U-test comparing with each CPET parameter of subjects with GOLD stages III and IV.

Abbreviations: CPET, cardiopulmonary exercise testing; f_R, breathing frequency; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SD, standard deviation; Te, expiratory time; Ti/Ttot, inspiratory duty cycle; V_D, physiological dead space; V_D/V_T, dead space to tidal volume ratio; V’_E, minute ventilation; V’_E/V’_CO2, ventilatory equivalent for carbon dioxide; V’_O2, oxygen uptake; V_T, tidal volume; V_T ex, expiratory tidal volume; V_T ex/Te; mean expiratory flow.

Figure 2 Results of cardiopulmonary exercise testing at peak exercise in the various GOLD stages (stages I–IV) (n=55). (A) Expiratory tidal volume at peak exercise in the various GOLD stages. (B) Mean expiratory flow (V_T ex/Te) at peak exercise in the various GOLD stages. (C) Breathing frequency (f_R) at peak exercise in the various GOLD stages. (D) Minute ventilation (V’_E) at peak exercise in the various GOLD stages. (E) Oxygen uptake (V’_O2) at peak exercise in the various GOLD stages. **p<0.01 by the Mann–Whitney U-test.

Abbreviations: f_R, breathing frequency; GOLD, Global Initiative for Chronic Obstructive Lung Disease; NS, not significant by the Mann–Whitney U-test; V’_E, minute ventilation; V’_O2, oxygen uptake; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow.

Table 6 Spearman’s Rank Correlation Coefficient Between Parameters of Respiratory Impedance at Rest, Spirometry, and Cardiopulmonary Exercise Testing at Rest (n=55)

	VT ex		VT ex/Te		fR		V’E		V’O2		VD/VT
Oscillometry
R5
Inspiratory	−0.260	NS	−0.193	NS	0.236	NS	−0.065	NS	−0.111	NS	0.175	NS
Expiratory	−0.176	NS	−0.048	NS	0.222	NS	0.050	NS	−0.105	NS	0.108	NS
R20
Inspiratory	−0.223	NS	−0.105	NS	0.252	NS	−0.002	NS	−0.033	NS	0.160	NS
Expiratory	−0.133	NS	−0.051	NS	0.150	NS	0.008	NS	−0.050	NS	0.062	NS
R5-R20
Inspiratory	−0.247	NS	−0.177	NS	0.220	NS	−0.052	NS	−0.136	NS	0.150	NS
Expiratory	−0.174	NS	−0.140	NS	0.182	NS	−0.031	NS	−0.189	NS	0.094	NS
X5
Inspiratory	0.365	**	0.246	NS	−0.257	NS	0.152	NS	0.289	*	−0.338	*
Expiratory	0.143	NS	0.119	NS	−0.153	NS	−0.005	NS	0.114	NS	−0.245	NS
Fres
Inspiratory	−0.356	**	−0.278	*	0.241	NS	−0.148	NS	−0.335	*	0.385	**
Expiratory	−0.174	NS	−0.194	NS	0.155	NS	−0.038	NS	−0.220	NS	0.303	*
ALX
Inspiratory	−0.372	**	−0.250	NS	0.258	NS	−0.155	NS	−0.296	*	0.314	*
Expiratory	−0.160	NS	−0.109	NS	0.179	NS	0.019	NS	−0.132	NS	0.217	NS
Spirometry
FVC	0.429	**	0.503	**	−0.093	NS	0.434	**	0.506	**	−0.156	NS
FEV1	0.352	**	0.419	**	−0.136	NS	0.304	*	0.467	**	−0.253	*
FEV1/FVC	0.039	NS	0.131	NS	−0.004	NS	0.006	NS	0.143	NS	−0.180	NS

Notes: *p<0.05; **p<0.01.

Abbreviations: ALX, low-frequency reactance area; FEV₁, forced expiratory volume in 1 second; f_R, breathing frequency; Fres, resonant frequency; FVC, forced vital capacity; NS, not significant; R5 and R20, respiratory system resistance at 5 and 20 Hz, respectively; Te, expiratory time; V’_E, minute ventilation; V’_O2, oxygen uptake; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow; X5, respiratory system reactance at 5 Hz.

Table 7 Spearman’s Rank Correlation Coefficient Between Parameters of Respiratory Impedance at Rest, Spirometry, and Cardiopulmonary Exercise Testing at Peak Exercise (n=55)

	VT ex		VT ex/Te		fR		V’E		V’O2		VD/VT
Oscillometry
R5
Inspiratory	−0.560	**	−0.487	**	0.111	NS	−0.491	**	−0.404	**	0.480	**
Expiratory	−0.413	**	−0.329	**	0.063	NS	−0.388	**	−0.322	*	0.358	**
R20
Inspiratory	−0.490	**	−0.426	**	0.113	NS	−0.438	**	−0.327	*	0.384	**
Expiratory	−0.297	*	−0.241	NS	0.020	NS	−0.309	*	−0.207	NS	0.252	NS
R5-R20
Inspiratory	−0.558	**	−0.459	**	0.136	NS	−0.457	**	−0.432	**	0.510	**
Expiratory	−0.522	**	−0.427	**	0.063	NS	−0.486	**	−0.439	**	0.422	**
X5
Inspiratory	0.631	**	0.537	**	−0.163	NS	0.520	**	0.516	**	−0.620	**
Expiratory	0.488	**	0.446	**	−0.049	NS	0.463	**	0.419	**	−0.463	**
Fres
Inspiratory	−0.676	**	−0.586	**	0.138	NS	−0.566	**	−0.568	**	0.677	**
Expiratory	−0.577	**	−0.533	**	0.027	NS	−0.564	**	−0.514	**	0.554	**
ALX
Inspiratory	−0.658	**	−0.553	**	0.155	NS	−0.541	**	−0.537	**	0.607	**
Expiratory	−0.517	**	−0.463	**	0.057	NS	−0.489	**	−0.445	**	0.437	**
Spirometry
FVC	0.770	**	0.798	**	0.115	NS	0.756	**	0.718	**	−0.550	**
FEV1	0.875	**	0.871	**	0.155	NS	0.903	**	0.823	**	−0.715	**
FEV1/FVC	0.496	**	0.477	**	0.168	NS	0.556	**	0.470	**	−0.453	**

Notes: *p<0.05; **p<0.01.

Abbreviations: ALX, low-frequency reactance area; f_R, breathing frequency; FEV₁, forced expiratory volume in 1 second; Fres, resonant frequency; FVC, forced vital capacity; NS, not significant; R5 and R20, respiratory system resistance at 5 and 20 Hz, respectively; Te, expiratory time; V’_E, minute ventilation; V’_O2, oxygen uptake; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow; X5, respiratory system reactance at 5 Hz.

Figure 3 Results of univariate analyses and Spearman’s rank correlation coefficient analyses between inspiratory resonant frequency (Fres-ins) at rest and ventilatory parameters of cardiopulmonary exercise testing (CPET) (n=55). In each figure, the graphs on the left show the results of Fres-ins at rest and CPET ventilatory parameters at peak exercise, while those on the right show the results of Fres-ins at rest and ventilatory parameters at rest, respectively. (A) Fres-ins and expiratory tidal volume (V_T ex). (B) Fres-ins and mean expiratory flow (V_T ex/Te). (C) Fres-ins and breathing frequency (f_R). (D) Fres-ins and minute ventilation (V’_E). (E) Fres-ins and oxygen uptake (V’_O2). *p<0.05; **p<0.01.

Abbreviations: CPET, cardiopulmonary exercise testing; f_R, breathing frequency; Fres-ins, inspiratory resonant frequency; NS, not significant; R², R-squared; r_S, Spearman’s rank correlation coefficient; std β, standardized regression coefficient estimate; V’_E, minute ventilation; V’_O2, oxygen uptake; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow.

Figure 4 Results of Spearman’s rank correlation coefficient and univariate analyses of the correlation between inspiratory resonant frequency (Fres-ins) at rest and ventilatory parameters of cardiopulmonary exercise testing (CPET) at peak exercise (n=55).Interaction analyses were performed for Fres-ins and natural logarithms of exertional ventilatory parameters of CPET. All the analyses were statistically significant (p<0.01). (A) Fres-ins and expiratory tidal volume (V_T ex). (B) Fres-ins and mean expiratory flow (V_T ex/Te). (C) Fres-ins and minute ventilation (V’_E). (D) Fres-ins and oxygen uptake (V’_O2).

Abbreviations: β, unstandardized regression coefficient estimate; CPET, cardiopulmonary exercise testing; Fres-ins, inspiratory resonant frequency; R², R-squared; V’_E, minute ventilation; V’_O2, oxygen uptake; V_T ex, expiratory tidal volume; V_T ex/Te, mean expiratory flow.