Figures
- Fig. 1.—
Changes in constant-load exercise endurance time (ET) are shown from baseline (day −5) for placebo (○) and tiotropium (•). Data are presented as mean±sem. *: p<0.05 between groups.
- Fig. 2.—
Intensity of dyspnoea (“breathing discomfort”) during constant-load cycle exercise was significantly reduced at isotime after treatment with tiotropium (b) as compared to placebo (a). Tiotropium allowed patients to exercise significantly longer before reaching the same level of intolerable dyspnoea. ET: exercise endurance time; ▪: day −5; ▴: day 0; ♦: day 21; •: day 42. *: p<0.05 during treatment (days 0, 21 and 42) as compared to baseline (day −5).
- Fig. 3.—
Operating lung volumes at rest and during exercise at baseline (▪---) and after 42 days (•––) of treatment with placebo (a; n=91) and tiotropium (b; n=96). TLC: total lung capacity; IRV: inspiratory reserve volume; EILV: end-inspiratory lung volume; VT: tidal volume; EELV: end-expiratory lung volume; IC: inspiratory capacity.
- Fig. 4.—
Inter-relationships between improvements in response to treatment with tiotropium (n=96), i.e. differences (Δ) calculated as values at day 42 minus values at day −5 baseline. ET: endurance time; BorgISO: exertional dyspnoea intensity at isotime; ICISO: inspiratory capacity at isotime; % pred: % predicted.
Tables
- Table 1
Subject characteristics at study entry (day −15) and at pretreatment baseline (pulmonary function: pre-dose on day 0; exercise: day −5)
Tiotropium Placebo Study entry Baseline Study entry Baseline Subjects n 96 91 Sex, M:F 68:28 70:21 Age yrs 61.5±5.9 59.4±8.0 Body mass index kg·m−2 26.8±4.6 26.2±5.0 Smoking history pack-yrs 50.2±22.4 52.1±30.7 Current smokers n 37 42 Pulmonary function DL,CO mL·min−1·mmHg−1 (% pred) 15.0±5.7 (56±19) 15.4±5.9 (56±20) FEV1 L (% pred) 1.22±0.45 (41±13) 1.25±0.46 (42±13) 1.27±0.45 (41±12) 1.29±0.45 (42±12) FVC L (% pred) 2.64±0.82 (71±16) 2.73±0.80 (74±17) 2.79±0.81 (73±17) 2.92±0.86 (75±17) FEV1/FVC % 46.2±9.9 45.7±10.3 45.5±9.4 44.6±9.4 SGaw 1·cmH2O−1·s−1 0.036±0.021 0.038±0.026 0.037±0.023 0.036±0.017 IC L 2.23±0.78 2.19±0.69 2.20±0.68 2.18±0.62 FRC L (% pred) 5.27±1.00 (161±30) 5.30±1.04(161±28) 5.37±1.24 (160±30) 5.37±1.16 (160±29) TLC L (% pred) 7.51±1.34 (120±17) 7.49±1.34 (120±18) 7.57±1.42 (118±15) 7.54±1.37 (118±15) RV L (% pred) 4.49±0.94 (199±42) 4.42±0.99 (197±43) 4.45±1.21 (197±48) 4.37±1.11 (196±48) Peak exercise# Work rate W 78±32 59±24 79±30 60±22 V'O2 L·min−1 1.26±0.45 1.22±0.42 1.28±0.35 1.26±0.36 V'O2 mL·kg−1·min−1 16.0±4.6 15.5±4.3 16.7±4.3 16.4±4.5 Heart rate beats·min−1 123±19 120±19 127±20 125±20 V'E L·min−1 42.3±15.7 41.4±13.7 44.3±13.7 44.2±14.6 Sa,O2 % 92.7±4.6 93.5±3.7 Data are presented as mean±sd unless otherwise stated
M: male
F: female
DL,CO: diffusing capacity for carbon monoxide
FEV1: forced expiratory volume in one second
FVC: forced vital capacity
SGaw: specific airway conductance
IC: inspiratory capacity
FRC: functional residual capacity
TLC: total lung capacity
RV: residual volume
V'O2: oxygen consumption
V'E: minute ventilation
Sa,O2: oxygen saturation measured by pulse oximetry
#: symptom-limited incremental exercise at study entry and constant-load exercise at baseline (measurements are averages of the last 30 s of loaded exercise)
- Table 2
Baseline (day −5) measurements during constant-load exercise at 75% maximal work capacity (Wmax)
Tiotropium Placebo Subjects n 96 91 Work rate W 59±24 60±22 Endurance time s 467±270 517±310 V'E L·min−1 Rest 13.2±3.5 13.3±3.5 Isotime 40.5±13.8 42.7±14.4 Peak 41.4±13.7 44.2±14.6 fR breaths·min−1 Rest 18.2±4.5 18.4±4.8 Isotime 29.9±5.8 29.4±6.5 Peak 30.9±5.8 30.8±6.8 VT L Rest 0.76±0.23 0.76±0.27 Isotime 1.38±0.45 1.48±0.47 Peak 1.36±0.43 1.46±0.46 IC L Rest 2.25±0.68 2.33±0.62 Isotime 1.85±0.60 1.94±0.56 Peak 1.80±0.61 1.92±0.55 IRV L Rest 1.49±0.62 1.56±0.56 Isotime 0.46±0.33 0.47±0.32 Peak 0.43±0.40 0.46±0.33 Dyspnoea Borg Rest 0.9±1.1 0.7±0.9 Isotime 6.2±2.4 5.4±2.2 Peak 6.8±2.3 6.4±2.1 Data are presented as mean±sd
V'E: minute ventilation
fR: breathing frequency
VT: tidal volume
IC: inspiratory capacity
IRV: inspiratory reserve volume
- Table 3
Treatment differences in lung function parameters for the tiotropium group as compared to the placebo group
Trough Response Peak Response Day 21 Day 42 Day 0 Day 21 Day 42 FEV1 L 0.10±0.03*** 0.12±0.03*** 0.17±0.02# 0.22±0.03# 0.22±0.04# FVC L 0.19±0.06*** 0.25±0.06# 0.37±0.04# 0.41±0.06# 0.43±0.06# FEV1/FVC % 0.8±0.6 0.3±0.6 0.5±0.6 1.5±0.7* 1.4±0.8 SGaw 1·cmH2O−1·sec−1 0.015±0.006* 0.006±0.002** 0.016±0.002# 0.029±0.007# 0.022±0.003# IC L 0.10±0.05* 0.10±0.05* 0.20±0.04# 0.25±0.06*** 0.24±0.06*** RV L −0.23±0.10* −0.36±0.09*** −0.50±0.08# −0.51±0.10# −0.56±0.10# FRC L −0.17±0.08* −0.30±0.08*** −0.41±0.07# −0.41±0.08# −0.45±0.08# RV/TLC % −2.2±0.8** −3.0±0.8*** −4.9±0.6# −5.8±0.9# −6.0±0.9# FRC/TLC % −1.6±0.6** −2.1±0.6*** −3.5±0.5# −3.9±0.7# −4.0±0.7# TLC L −0.07±0.08 −0.20±0.08* −0.21±0.08** −0.15±0.09 −0.19±0.09* Data are presented as tiotropium–placebo, means adjusted for centre and baseline±se
FEV1: forced expiratory volume in one second
FVC: forced vital capacity
SGaw: specific airway conductance
IC: inspiratory capacity
RV: residual volume
FRC: functional residual capacity
TLC: total lung capacity
*: p<0.05
**: p<0.01
***: p<0.001
#: p<0.0001
- Table 4
Treatment differences in exercise test parameters for the tiotropium group compared with the placebo group
Day 0 Day 21 Day 42 Endurance time s 40±28 67±32* 105±40** Rest Dyspnoea Borg −0.1±0.1 0.0±0.1 −0.1±0.1 IC L 0.25±0.04# 0.21±0.04# 0.23±0.05# VT L 0.03±0.02 −0.02±0.02 0.00±0.03 fR breaths·min−1 0.2±0.4 0.6±0.5 0.6±0.5 V'E L·min−1 0.2±0.4 0.2±0.4 0.4±0.4 IRV L 0.22±0.05# 0.23±0.05# 0.23±0.05# Isotime exercise Dyspnoea Borg −0.5±0.2* −0.7±0.3* −0.9±0.3** IC L 0.21±0.04# 0.19±0.05# 0.18±0.05*** VT L 0.09±0.03*** 0.15±0.03# 0.11±0.03*** fR breaths·min−1 −0.6±0.5 −0.7±0.6 −0.5±0.6 V'E L·min−1 1.8±0.7* 3.3±1.1** 3.0±0.8*** IRV L 0.13±0.04*** 0.08±0.04* 0.08±0.04* Peak exercise Dyspnoea Borg −0.2±0.2 −0.1±0.2 −0.1±0.3 IC L 0.15±0.04*** 0.22±0.05# 0.15±0.05** VT L 0.10±0.03*** 0.11±0.03*** 0.10±0.03*** fR breaths·min−1 0.10±0.48 0.33±0.50 0.59±0.54 V'E L·min−1 2.9±0.8*** 4.0±1.1*** 4.1±0.7# IRV L 0.07±0.04 0.14±0.05** 0.07±0.05 Data are presented as tiotropium–placebo, means adjusted for centre and baseline±se
IC: inspiratory capacity
VT: tidal volume
fR: breathing frequency
V'E: minute ventilation
IRV: inspiratory reserve volume
*: p<0.05
**: p<0.01
***: p<0.001
#: p<0.0001
