Efficacy of tiotropium and olodaterol combination therapy on dynamic lung hyperinflation evaluated by hyperventilation in COPD: an open-label, comparative before and after treatment study

Figures & data

Figure 1 Method for measuring dynamic lung hyperinflation by hyperventilation.

Abbreviations: IC, inspiratory capacity; bpm, breaths/min; DLH, dynamic lung hyperinflation.

Figure 2 Details of dynamic lung hyperinflation measurement method using spirometer.

Abbreviations: IC, inspiratory capacity; bpm, breaths/min; IC_rest, IC at rest; IC₂₀, IC at 20 bpm; IC₃₀, IC at 30 bpm; IC₄₀, IC at 40 bpm.

Table 1 Characteristics of patients and comparison of lung function before and after treatment

	Before	After
n	33	33
Age, years	76.2±1.2
Sex (male/female)	32/1	32/1
Smoking history, pack × year	53.3±5.8
Past smoker, n	30
Current smoker, n	3
BMI, kg/m^2	22.7±0.4
CAT	13.7±1.4	10.8±1.2*
mMRC	1.3±0.2	1.0±0.2
%VC, %	101.1±2.8	105.1±2.2*
IC, L	2.32±0.09	2.32±0.06
FEV1, L	1.58±0.10	1.67±0.08 **
FEV1, %	61.1±3.2	63.9±2.6 **
FEV1/FVC, %	51.4±1.9	51.6±1.8 **
%FRC, %	99.7±3.9
%RV, %	158.8±8.3
%TLC, %	125.6±3.4
RV/TLC, %	42.4±1.8
%DLCO, %	67.4±3.5
GOLD stage (1, 2, 3, 4)	4/21/7/1
Treatment with inhaled agents at before including study
No drug, n	5
LAMA, n	13
LABA, n	2
LAMA+LABA, n	4
LABA+ICS, n	2
LAMA±LABA±ICS, n	7

Notes: Values represent mean ± standard error of the mean; *p<0.05 and **p<0.01 vs before treatment.

Abbreviations: BMI, body mass index; CAT, COPD assessment test; mMRC, Modified Medical Research Council dyspnea scale, VC, vital capacity; IC, inspiratory capacity; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; DLCO, lung-diffusion capacity for carbon monoxide; LAMA, long-acting muscarinic antagonist; LABA, long-acting beta 2 agonist; ICS, inhaled corticosteroid.

Table 2 Comparison of dynamic lung hyperinflation following hyperventilation and 6-min walking test (6MWT) before and after treatment

	Before	After
n	33	33
ICrest, L	2.39±0.08	2.42±0.09
IC20, L	2.25±0.09	2.41±0.09 *
IC30, L	2.12±0.09	2.27±0.09 **
IC40, L	1.99±0.10	2.15±0.10 **
–IC20, L	–0.13±0.05	−0.02±0.05 *
–IC30, L	–0.27±0.05 ^††	−0.16±0.06 *^†
–IC40, L	–0.40±0.06 ^††	−0.27±0.06 *^††
ΔIC20, %	–5.6±2.2	0.5±2.5 *
ΔIC30, %	–11.6±2.3 ^††	−5.5±2.8 *^†
ΔIC40, %	–16.9±2.7 ^††	−10.8±2.7 **^††
6MWD, m	460.2±19.4	477.1±18.4 *
Pre SpO2, %	95.3±0.3	95.2±0.4
Lowest SpO2, %	87.3±0.9	87.9±0.9
PRmin, bpm	73.4±2.3	72.4±2.6
PRmax, bpm	115.0±2.4	113.5±3.1
BSmin,	0.4±0.2	0.3±0.2
BSmax,	5.2±0.5	4.6±0.4

Notes: Values represent mean ± standard error of the mean; *p<0.05 and **p<0.01 vs before treatment; ^†p<0.05 and ^††p<0.01 vs –IC₂₀ or ΔIC₂₀.

Abbreviations: IC, inspiratory capacity; bpm, breaths/min; IC_rest, IC at rest; IC₂₀, IC at 20 bpm; –IC₂₀, decrease in IC from IC_rest to IC₂₀; ΔIC₂₀, change in IC from IC_rest to IC₂₀; IC₃₀, IC at 30 bpm; –IC₃₀, decrease in IC from IC_rest to IC₃₀; ΔIC₃₀, change in IC from IC_rest to IC₃₀; IC₄₀, IC at 40 bpm; –IC₄₀, decrease in IC from IC_rest to IC₄₀; ΔIC₄₀, change in IC from IC_rest to IC₄₀; 6MWD, 6-min walking distance; SpO₂, percutaneous oxygen saturation; PR_min, minimum pulse rate; PR_max, maximum pulse rate; BS_min, minimum modified Borg scale; BS_max, maximum modified Borg scale.

Figure 3 Comparison of dynamic lung hyperinflation following hyperventilation before and after treatment. *P<0.05 vs before combined treatment with tiotropium and olodaterol.

Abbreviations: Tio, Tiotropium; Olo, Olodaterol; IC, inspiratory capacity; bpm, breaths/min; IC_rest, IC at rest; −IC₂₀, decrease in IC from IC_rest to IC at 20 bpm; −IC₃₀, decrease in IC from IC_rest to IC at 30 bpm; −IC₄₀, decrease in IC from IC_rest to IC at 40 bpm.

Table 3 Correlation of changes in DLH, FEV₁, exercise tolerance, and dyspnea with treatment

	FEV^1 (L)	6MWD (m)	BSmax
ICrest	0.30	0.25	0.28
IC20	0.06	0.05	0.06
IC30	0.22	0.15	0.18
IC40	0.13	0.18	0.06
–IC20	−0.23	−0.20	–0.17
–IC30	−0.06	−0.14	–0.13
–IC40	−0.17	−0.12	–0.14
ΔIC20	−0.24	−0.18	–0.09
ΔIC30	−0.01	−0.05	–0.10
ΔIC40	−0.03	−0.02	−0.17

Notes: Values represent the means. The value of change associated with treatment was calculated as the post-value minus the pre-value.

Abbreviations: IC, inspiratory capacity; IC_rest, IC at rest; IC₂₀, IC at 20 bpm; –IC₂₀, decrease in IC from IC_rest to IC₂₀; ΔIC₂₀, change in IC from IC_rest to IC₂₀; IC₃₀, IC at 30 bpm; –IC₃₀, decrease in IC from IC_rest to IC₃₀; ΔIC₃₀, change in IC from IC_rest to IC₃₀; IC₄₀, IC at 40 bpm; –IC₄₀, decrease in IC from IC_rest to IC₄₀; ΔIC₄₀, change in IC from IC_rest to IC₄₀. FEV₁, forced expiratory volume in 1 s; 6MWD, 6-min walking distance; BS_max, maximum modified Borg scale.

Figure 4 Correlations of changes in value associated with treatment between 6MWD and FEV₁(A), IC₄₀ (B) or −IC₄₀ (C) and between IC₄₀ and FEV₁(D). IC₄₀, inspiratory capacity (IC) following 30-s hyperventilation at 40 breaths/min; −IC₄₀, change in IC at rest to IC_40.The value of change associated with treatment was calculated as the post-value minus the pre-value.

Abbreviations: Ch, change in value by treatment; FEV₁, forced expiratory volume in 1 s; 6MWD, 6-min walking distance; IC, inspiratory capacity; IC₄₀, IC at 40 breaths/min; −IC₄₀, decrease in IC from IC at rest to IC_40.