Figures
- Fig. 1.—
A flow chart of study assessments.
- Fig. 2.—
The disposition of patients in the study.
Tables
- Table 1
Demographics and baseline characteristics
Characteristic Tiotropium-AM Tiotropium-PM Placebo Total Total treated 33 32 30 95 Male sex n (%) 22 (67) 21 (66) 23 (77) 66 (70) Age yrs 66.7 (48–77) 65.1 (54–79) 67.6 (49–82) 66.4 (48–82) Weight kg 70.6 (46–113) 72.8 (40–100) 70.5 (44–109) 71.3 (40–113) Height cm 166.8 (134–182) 168.1 (140–192) 169.2 (152–188) 168.0 (134–192) Smoking history Current smoker n (%) 12 (36) 9 (28) 9 (30) 30 (32) Pack-yrs 50.4 (10–186) 46.5 (12–120) 51.6 (10–130) 49.5 (10–186) FEV1 L 0.82±0.27 0.87±0.32 0.81±0.31 0.84±0.30 FVC L 1.89±0.62 2.01±0.80 1.95±0.62 1.95±0.68 FEV1/FVC % 45±10 46±14 43±13 44±12 FEV1 % predicted 33±12 33±13 31±12 32±12 Pa,O2 mmHg 66.0±6.9 64.1±6.8 63.5±7.8 64.6±7.2 Low Pa,O2 stratum ≤65 mmHg n (%) 13 (39.4) 18 (56.3) 15 (50.0) 46 (48.4) High Pa,O2 stratum 66–75 mmHg n (%) 20 (60.6) 14 (43.8) 15 (50.0) 49 (51.6) -
Data are presented as mean (range) or mean±sd unless otherwise stated
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FEV1: forced expiratory volume in one second
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FVC: forced vital capacity
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Pa,O2: awake arterial oxygen tension
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Total randomised patients: n=95. All patients were Caucasian
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1 mmHg=0.133 kPa
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- Table 2
Oxygen saturation (%) during rapid eye movement (REM) sleep and differences between treatment groups at end of study
Comparison Tiotropium-AM Tiotropium-PM Tiotropium pooled Placebo Difference in % points p-value 95% CI Subjects n 19 17 36 11 Tiotropium-AM versus placebo 89.97 (0.59) 87.56 (0.76) 2.41 0.016 0.48–4.33 Tiotropium-PM versus placebo 89.98 (0.62) 87.56 2.42 0.020 0.41–4.43 Tiotropium pooled versus placebo 89.98 (0.41) 87.56 2.41 0.008 0.68–4.15 -
Data are presented as mean (se) unless otherwise stated and are from the patient population with total sleep time of at least 2 h
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Some patients did not have any REM sleep at baseline or end of study
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Means are adjusted for baseline arterial oxygen saturation (Sa,O2) and arterial oxygen tension. Overall mean baseline Sa,O2 during REM sleep=88.74%
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- Table 3
Oxygen saturation (%) during total sleep time and differences between treatment groups at end of study
Comparison Tiotropium-AM Tiotropium-PM Tiotropium pooled Placebo Difference in % points p-value 95% CI Subjects n 21 18 39 13 Tiotropium-AM versus placebo 89.83 (0.84) 87.82 (1.05) 2.01 0.141 −0.69–4.71 Tiotropium-PM versus placebo 90.88 (0.92) 87.82 3.06 0.035 0.23–5.91 Tiotropium pooled versus placebo 90.31 (0.61) 87.82 2.49 0.047 0.02–4.93 -
Data are presented as mean (se) unless otherwise stated and are from the patient population with total sleep time of at least 2 h
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Means are adjusted for baseline arterial oxygen saturation (Sa,O2) and arterial oxygen tension
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Overall mean baseline Sa,O2 during total sleep time=89.58%
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- Table 4
Effect of tiotropium (pooled AM and PM) versus placebo on duration of sleep stages, latency to persistent sleep and latency to rapid eye movement (REM) sleep
Stage Overall mean baseline Tiotropium Placebo Difference p-value Subjects n 40 16 Awake 120.3 110.0 (9.8) 120.3 (15.7) −10.3 0.585 Stage I 40.5 39.4 (4.9) 50.8 (7.7) −11.4 0.219 Stage II 158.8 168.1 (10.1) 147.0 (16.1) 21.1 0.275 Stage III/IV 40.4 35.2 (4.6) 47.9 (7.3) −12.7 0.146 REM 37.8 52.1 (4.6) 51.1 (7.4) 1.0 0.906 Total sleep time 277.4 294.4 (11.1) 297.8 (17.6) −3.4 0.871 Total sleep period 397.7 408.7 (12.0) 408.2 (19.2) 0.5 0.982 Latency to persistent sleep 30.8 32.2 (5.3) 40.9 (8.0) −8.7 0.370 Subjects n 36 16 Latency to REM sleep 120.4 97.5 (9.5) 89.7 (17.0) 7.8 0.695 Subjects n 36 12 -
Data are presented as mean (SE) unless otherwise stated and are from the patient population with total sleep time of at least 2 h
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Means are adjusted for baseline stage duration and baseline arterial oxygen tension
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Latency to persistent sleep is the time in minutes to the first period of stage II sleep
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- Table 5
Effect of tiotropium (pooled AM and PM) versus placebo on pre- and post-sleep forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)
Tiotropium Placebo Difference p-value 95% CI Pre-sleep FEV1 L 0.91 (0.03) 0.72 (0.05) 0.19 0.002 0.07–0.31 Patients n 40 15 Post-sleep FEV1 L 0.81 (0.02) 0.64 (0.03) 0.17 0.0001 0.09–0.26 Patients n 38 16 Pre-sleep FVC L 2.18 (0.07) 1.87 (0.12) 0.31 0.027 0.04–0.58 Patients n 40 15 Post-sleep FVC L 1.94 (0.06) 1.58 (0.09) 0.36 0.001 0.15–0.57 Patients n 38 16 -
Data are presented as mean (se) from the patient population with total sleep time of at least 2 h (n=56)
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Means are adjusted for end-point baseline and baseline arterial oxygen tension
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Overall mean baseline FEV1: pre-sleep: 0.84 L
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post-sleep: 0.76 L
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Overall mean baseline FVC: pre-sleep: 2.03 L; post-sleep: 1.79 L
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- Table 6
Correlation between mean oxygen saturation during rapid eye movement (REM) sleep and forced expiratory volume in one second (FEV1)
Pearson correlation coefficient p-value Pre-sleep FEV1 Baseline visit 0.29 0.045 End-of-treatment visit 0.42 0.003 Post-sleep FEV1 Baseline visit 0.28 0.064 End-of-treatment visit 0.36 0.013 -
Data are from patient population with total sleep time of at least 2 h who also had REM sleep (n=47)
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