Efficacy of tiotropium and indacaterol monotherapy and their combination on dynamic lung hyperinflation in COPD: a random open-label crossover study

Figures & data

Table 1 Characteristics at baseline of 23 patients with COPD

Age, years	74.7±1.5
Sex (male/female)	21/2
Smoking history, packs/year	55.4±4.1
BMI, kg/m^2	22.7±0.5
CAT score	12±1.5
P-ADL score	215±2
VC, %	96.2±5.7
IC, L	1.98±0.12
FEV1, L	1.48±0.12
FEV1, %	59.0±4.8
GOLD stage (1/2/3/4)	3/13/4/3
FEV1/FVC, %	47.4±3.2
FRC, %	125.4±8.5
RV, %	181.3±10.6
TLC, %	129.1±4.6
RV/TLC, %	47.7±2.1
Raw	2.3±0.21
DLCO, %	69.7±4.4

Note: Data expressed as mean ± standard error of mean.

Abbreviations: BMI, body-mass index; CAT, COPD-assessment test; P-ADL, pulmonary emphysema activity of daily life; VC, vital capacity; IC, inhaled corticosteroid; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; R_aw, airway resistance; DL_CO, lung-diffusion capacity for carbon monoxide.

Table 2 Results of questionnaires on health status and activity of daily life (ADL) and of the pulmonary function test

	Baseline	Tiotropium (Tio)	Indacaterol (Ind)	Tio + Ind
CAT score	12±1.5	9±1.5**	9.5±1.6*	7.4±1.2**
P-ADL score	214.8±2.1	214.5±0.15	215±2.3	217.0±1.7*,#
VC, L	3.34±0.15	3.33±0.16	3.31±0.17	3.33±0.15
FVC, L	3.1±0.16	3.09±0.15	3.09±0.16	3.16±0.17
FEV1, L	1.48±0.12	1.55±0.12**	1.55±0.13*	1.63±0.14**,§
FRC, L	4.2±0.23	4.18±0.27	4.06±0.25	4.05±0.23
RV, L	3.11±0.2	3.07±0.25	3.18±0.26	2.99±0.23
TLC, L	6.48±0.22	6.35±0.25	6.39±0.26	6.37±0.27
RV/TLC, %	47.7±2.1	47±2.2	47.2±2.2	46.1±2.1
Raw, cmH2O·L^−1·second	2.3±0.21	1.87±0.15**	2.05±0.22	1.68±0.15**,#
Rrs5, cmH2O·L^−1·second	2.72±0.3	2.73±0.26	2.63±0.22	2.78±0.27
Rrs5–Rrs20, cmH2O·L^−1·second	0.74±0.11	0.66±0.08	0.67±0.09	0.71±0.11
Xrs5, cmH2O·L^−1·second	−1.57±0.3	−1.37±0.25	−1.33±0.3	−1.21±0.26
Fres, Hz	15.5±1.4	14.3±1.2	13.4±1.3	12.6±1.4*
ΔXrs5, cmH2O·L^−1·second	−0.75±0.26	−0.7±0.26	−0.59±0.27	−0.06±0.3*,#,§§

Notes: Data expressed as mean ± standard error of mean.

* P<0.05,

** P<0.01 vs baseline;

# P<0.05 vs Ind;

§ P<0.05,

§§ P<0.01 vs Tio.

Abbreviations: CAT, COPD-assessment test; P-ADL, pulmonary emphysema activity of daily life; VC, vital capacity; FEV₁, forced expiratory volume in 1 second; FRC, functional residual capacity; FVC, forced vital capacity; R_aw, airway resistance; Rrs₅, respiratory resistance at 5 Hz; Rrs₂₀, respiratory resistance at 20 Hz; RV, residual volume; TLC, total lung capacity; Xrs₅, respiratory reactance at 5 Hz; F_res, resonant frequency; ΔXrs₅, within-breath changes in Xrs₅.

Table 3 Dynamic lung hyperinflation following incremental hyperventilation

	Baseline	Tiotropium (Tio)	Indacaterol (Ind)	Tio + Ind
ICrest, L	1.98±0.12	2.08±0.12	2.02±0.12	2.06±0.13
IC20, L	1.91±0.13	2.04±0.13**	1.95±0.13	2.01±0.14
IC30, L	1.84±0.13	1.96±0.15*,##	1.84±0.14	1.99±0.15*,#
IC40, L	1.71±0.14	1.88±0.14*	1.79±0.15	1.9±0.15**
−IC20, L	−0.07±0.06	−0.04±0.04	−0.07±0.06	−0.05±0.04
−IC30, L	−0.14±0.05	−0.11±0.05	−0.19±0.06	−0.07±0.04#
−IC40, L	−0.27±0.06	−0.20±0.06	−0.23±0.08	−0.16±0.05*
ΔIC20, %	−3.3±2.9	−1.6±2.2	−3.8±2.9	−3±1.6
ΔIC30, %	−7.6±2.4	−6.5±2.4#	−10.5±2.7	−4.7±2#
ΔIC40, %	−14.9±3	−10.4±3	−12.7±3.7	−8.8±2.6*

Notes: Data expressed as mean ± standard error of mean.

* P<0.05,

** P<0.01 vs baseline;

# P<0.05,

## P<0.01 vs Ind.

Abbreviations: IC, inspiratory capacity; IC_rest, resting IC; IC₂₀, IC at 20 breaths/min; −IC₂₀, decrease in IC from IC_rest to IC₂₀; ΔIC₂₀, change in IC from IC_rest to IC₂₀; IC₃₀, IC at 30 breaths/min; −IC₃₀, decrease in IC from IC_rest to IC₃₀; ΔIC₃₀, change in IC from IC_rest to IC₃₀; IC₄₀, IC at 40 breaths/min; −IC₄₀, decrease in IC from IC_rest to IC₄₀; ΔIC₄₀, change in IC from IC_rest to IC₄₀.

Table 4 Exercise tolerance evaluated by shuttle-walk test

	Baseline	Tiotropium (Tio)	Indacaterol (Ind)	Tio + Ind
BSmax score	4.6±0.5	5.1±0.4	4.9±0.3	5.2±0.4
Lowest SpO2, %	89.5±0.3	88.5±1.6	89.2±1.5	89.6±1.3
PRmax, beats/min	111.6±3.6	111.0±4.4	111.8±3.4	109.8±3.8
Systolic BPmax, mmHg	158.1±5.4	154.5±4.5	157.2±4.4	153.1±4.5
Diastolic BPmax, mmHg	82.3±3.5	84.1±4.5	84.3±4.1	79.3±3.1
Walking distance, m	384.8±34.5	425.2±29.2*	430.0±35.6**	447.4±37.7**

Notes: Data expressed as mean ± standard error of mean.

* P<0.05,

** P<0.01 vs baseline.

Abbreviations: BS_max, Borg scale (modified) maximum; SpO₂, peripheral oxygen saturation; PR_max, maximum pulse rate; BP_max, maximum blood pressure.

Figure 1 Effects of tiotropium (Tio) and indacaterol (Ind) alone and the combination thereof.

Notes: Effect on inspiratory capacity (IC) at rest (IC_rest) and IC following metronome-paced incremental hyperventilation at rates of 20, 30, and 40 breaths/min (IC₂₀, IC₃₀, and IC₄₀, respectively). Data expressed as mean ± standard error of mean. *P<0.05, **P<0.01 vs baseline; ^#P<0.05, ^##P<0.01 vs Ind.

Figure 2 Effects of tiotropium (Tio) and indacaterol (Ind) alone and the combination of thereof.

Notes: Effect on changes in IC following metronome-paced incremental hyperventilation at rates of 20, 30, and 40 breaths/min (%Ch. ΔIC₂₀, IC₃₀, and IC₄₀, respectively) from IC at rest. Data expressed as mean ± standard error of mean. *P<0.05 vs baseline, ^#P<0.05 vs Ind.
Abbreviations: IC, inspiratory capacity; IC_rest, resting IC; IC₂₀, IC at 20 breaths/min; ΔIC₂₀, change in IC from IC_rest to IC₂₀; IC₃₀, IC at 30 breaths/min; ΔIC₃₀, change in IC from IC_rest to IC₃₀; IC₄₀, IC at 40 breaths/min; ΔIC₄₀, change in IC from IC_rest to IC₄₀.