Online depository Method Measurement of arterialised venous pH and partial pressure of carbon dioxide An arterialised venous blood sample was collected from a 20 gauge cannula that was inserted into a vein on the dorsum of the wrist or forearm. A 12 cm extension catheter was attached (dead space 0.2 millilitres) and pointed distally to allow blood to be sampled away from the hand. The cannula was flushed intermittently with normal saline to prevent clotting. An electric heating pad (Therathermī¤, Chattanooga Group, Hixon, Tennessee, USA) was wrapped around the participants forearm and hand, covering the cannula. The temperature of the forearm was monitored using a thermometer with the probe placed adjacent to the cannula, and an external display screen. Skin temperature was maintained between 42 - 45ºC [1, 2]. The heating pad was in place for a minimum of 20 minutes before sampling began. To account for dead space within the cannula and extension catheter, one millilitre (mL) of blood was withdrawn and discarded prior to collection of the arterialised venous sample. Then two mL of blood was withdrawn from the cannula into a three mL heparinised syringe. Air bubbles were expelled from the syringe and the sample was stored in ice until blood pH, partial pressure of carbon dioxide (PCO2) and lactate (La) levels were analysed using a Corning 175 Blood Gas Analyser (Medfield, MA). This was typically within 30 minutes of the sample being collected. Flow Expiratory flow was measured by a mesh screen pneumotachograph (3830B Hans Rudolph, Shawnee, Kansas, USA) placed between the full face mask and the expiratory port within the bilevel circuit. To keep the interface and dead space (195 mL) consistent, flow was measured during unassisted exercise by removing the expiratory port and tubing, leaving only the full face mask and pneumotachograph. The pneumotachograph was connected to a differential pressure transducer (Validyne DP45-14, ± 2.25 cmH2O, Validyne Engineering Corporation, Northridge, CA, 1 USA). The pressure transducer voltage output was amplified, displayed real time and recorded on a laptop using a data acquisition program (PhysioDAQxs, University of Sydney, NSW, Australia) with a sampling frequency of 100Hz. The pneumotachograph was calibrated prior to each test using a three litre syringe and the technique described by Tang et al [3]. The calibration file was used to determine whether an offset needed to be applied to zero the baseline, and the magnitude of the offset. A linear relationship between voltage and flow was assumed, and a conversion factor was obtained by calculating the average voltage output for one litre/second from the calibration file. Voltage output was converted to flow (litres/minute), and flow was integrated to give tidal volume (VT). Respiratory rate (RR) was calculated by counting the number of breaths on the flow trace during the final 20 seconds of the baseline period and minute ventilation (VE) was calculated by multiplying VT and RR. Subjective responses to pressure support during exercise At the end of each test with pressure support (PS), participants scored the effect of PS during exercise on the amount of “help” provided and “breathlessness” compared to usual unassisted walking on a 10 cm visual analogue scale (VAS). Results Table 4 Pairwise comparisons of walking unassisted, with sham pressure support, pressure support 10 cmH2O and pressure support 20 cmH2O for endurance time (seconds) after transformation using log(x) Comparison PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA Log(x) endurance time Mean (SD) vs Mean (SD) Mean difference (95% CI) p value Adjusted p value 2.446 (0.3456) vs 2.137 (0.234) 2.446 (0.3456) vs 2.217 (0.1548) 2.217 (0.1548) vs 2.137 (0.234) 2.446 (0.3456) vs 2.071 (0.2376) 2.217 (0.1548) vs 2.071 (0.2376) 2.071 (0.2376) vs 2.137 (0.234) 0.309 (0.078 to 0.540) 0.229 (0.080 to 0.378) 0.080 (-0.079 to .240) 0.375 (0.235 to 0.515) 0.146 (0.057 to 0.235) -0.066 (-0.273 to 0.141) 0.013 0.006 0.295 <0.001 0.004 0.499 0.039 0.012 NS <0.001 0.008 NS Log(x) of endurance time (seconds) data are presented. PS 20: pressure support 20 cmH 2O; UnA: unassisted exercise; PS 10: pressure support 10 cmH2O; Sham: sham pressure support; Adjusted p: p value adjusted using a sharper Bonferroni correction [17]; NS: not significant 2 Table 5 Descriptive data for physiological and subjective variables at rest, baseline, isotime and end exercise SpO2 % Rest Baseline Isotime End exercise HR (beats/min) Rest Baseline Isotime End exercise Dyspnoea (Borg) Rest Baseline Isotime End exercise RPE (Borg) Rest Baseline Isotime End exercise VE (L/min) Baseline Isotime End exercise RR (bpm) Baseline Isotime End exercise VT (L) Baseline Isotime End exercise pH Rest Baseline End exercise PCO2 (mmHg) Rest Baseline End exercise [La] (mmol/L) Rest Baseline End exercise SBP (mmHg) Rest Baseline End exercise DBP (mmHg) Rest Baseline End exercise MAP (mmHg) Rest Baseline End exercise Unassisted Sham PS PS 10 PS 20 94 ± 4 94 ± 4 84 ± 7 82 ± 10 94 ± 2 92 ± 3 82 ± 7 80 ± 7 94 ± 3 94 ± 2 87 ± 5 81 ± 7 94 ± 2 96 ± 2 88 ± 5 82 ± 8 87 ± 15 87 ± 15 116 ± 20 118 ± 23 86 ± 11 88 ± 13 115 ± 20 118 ± 18 85 ± 12 86 ± 14 113 ± 16 118 ± 16 85 ± 15 87 ± 14 109 ± 14 120 ± 18 0 (0 - 0.5) 0 (0 - 0.5) 3.7 ± 2.7 6.0 ± 2.9 0 (0 - 0.8) 0 (0 - 2.5) 4.4 ± 2.6 5.4 ± 2.4 0 (0 - 0.5) 0 (0 - 1) 2.7 ± 1.8 5.4 ± 2.6 0 (0 - 0.3) 0.5 (0 - 1) 2.0 ± 2.2 6.0 ± 2.7 0 (0 - 0.3) 0 (0 - 0.3) 4.5 ± 2.8 6.3 ± 2.8 0 (0 – 1.0) 0 (0 - 2.0) 4.5 ± 2.4 5.5 ± 2.3 0 ( 0 - 0.5) 0 (0 - 0.8) 2.9 ± 2.2 5.5 ± 2.7 0 (0 - 0.3) 0 (0 - 1.0) 2.8 ± 2.1 7.1 ± 3.0 9.237 ± 2.870 18.110 ± 5.056 19.543 ± 6.332 8.035 ± 1.693 15.265 ± 2.747 15.588 ± 2.722 9.765 ± 2.016 17.390 ± 3.390 19.023 ± 4.061 10.450 ± 3.740 17.261 ± 4.354 21.325 ± 5.293 29 ± 6 42 ± 9 47 ± 10 30 ± 8 40 ± 10 41 ± 10 28 ± 9 38 ± 9 42 ± 11 25 ± 9 34 ± 8 40 ± 9 0.332 ± 0.107 0.462 ± 0.136 0.471 ± 0.132 0.295 ± 0.094 0.412 ± 0.120 0.419 ± 0.131 0.384 ± 0.113 0.483 ± 0.143 0.505 ± 0.159 0.453 ± 0.179 0.539 ± 0.173 0.569 ± 0.174 7.379 ± 0.046 7.379 ± 0.046 7.352 ± 0.051 7.383 ± 0.039 7.374 ± 0.040 7.359 ± 0.039 7.379 ± 0.039 7.389 ± 0.040 7.356 ± 0.038 7.382 ± 0.031 7.421 ± 0.043 7.355 ± 0.048 50.7 ± 7.2 50.7 ± 7.2 53.9 ± 9.5 49.7 ± 7.4 50.3 ± 8.7 53.1 ± 8.2 49.5 ± 7.9 47.8 ± 7.1 53.4 ± 8.0 49.9 ± 6.6 43.9 ± 6.0 51.9 ± 8.6 1.1 ± 0.3 1.1 ± 0.3 1.7 ± 0.9 1.0 ± 0.2 0.9 ± 0.1 1.3 ± 0.4 1.1 ± 0.4 1.1 ± 0.4 1.7 ± 0.5 1.2 ± 0.5 1.2 ± 0.6 2.2 ± 1.0 124 ± 13 124 ± 13 158 ± 24 124 ± 11 125 ± 13 145 ± 23 121 ± 11 123 ± 14 150 ± 23 125 ± 14 118 ± 11 150 ± 20 88 ± 11 88 ± 11 90 ± 11 85 ± 11 89 ± 10 85 ± 13 85 ± 10 87 ± 11 90 ± 10 86 ± 10 85 ± 11 93 ± 11 100 ± 11 100 ± 11 113 ± 3 98 ± 10 101 ± 10 105 ± 14 97 ± 9 99 ± 11 110 ± 12 99 ± 11 96 ± 11 112 ± 12 Data are presented as mean ± SD or median (interquartile range). SpO2 %: oxygen saturation; HR: heart rate; RPE: rate of perceived exertion; VE: minute ventilation; RR: respiratory rate; VT: tidal volume; PCO2: arterialised venous carbon dioxide partial pressure; [La]: lactate; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; UnA: unassisted exercise; Sham PS: sham pressure support, PS 10: pressure support 10 cmH 2O; PS 20: pressure support 20 cmH2O; NA: not assessed 3 Baseline At baseline, there was a difference between the interventions with respect to SpO2, pH, PCO2 and VT (Table 6). Pairwise comparisons of the four conditions with a sharper Bonferroni [4] correction of p values, revealed that SpO2 was higher with PS 20 and PS 10 compared to unassisted breathing or sham PS. Compared to unassisted breathing, sham PS or PS 10, PS 20 increased pH (less acidic) and reduced PCO2. Pressure support 10 cmH2O at rest increased pH compared to sham PS, and reduced PCO2 compared to unassisted breathing and with sham PS. Tidal volume was higher with PS 20 compared to unassisted breathing and sham PS (Table 7). Table 6 Linear mixed model analysis of breathing unassisted, with sham pressure support, pressure support 10 cmH2O and pressure support of 20 cmH2O at baseline, isotime, end exercise and change from baseline to end exercise on oxygen saturation, pH, partial pressure of carbon dioxide, cardiovascular variables, dyspnoea, perceived exertion, lactate and ventilation SpO2 HR Dyspnoea RPE SBP DBP MAP pH PCO2 La RR VT VE Baseline Isotime End Exercise Change from baseline to end exercise p p p p <0.001 0.89 0.16 0.68 0.073 0.43 0.12 <0.001 <0.001 0.16 0.11 0.002 0.09 <0.001 0.16 0.006 0.013 NA NA NA NA NA NA <0.001 0.018 0.13 0.38 0.79 0.67 0.061 0.092 0.002 0.007 0.94 0.27 0.002 <0.001 0.003 0.015 0.32 0.15 0.31 0.045 0.014 0.001 0.001 <0.001 0.010 0.047 0.031 0.84 0.22 SpO2%: oxygen saturation; HR: heart rate; RPE: rate of perceived exertion; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; PCO2: arterialized venous carbon dioxide tension; La: lactate; RR: respiratory rate; VT: tidal volume; VE: minute ventilation; NA: not assessed 4 Table 7 Pairwise comparisons of breathing unassisted, with sham pressure support, pressure support 10 cmH2O and pressure support 20 cmH2O for oxygen saturation, pH, partial pressure of carbon dioxide and tidal volume at baseline Comparison Mean (SD) vs Mean (SD) Mean difference (95% CI) SpO2 PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 96 (2) vs 94 (4) 96 (2) vs 94 (2) 94 (2) vs 94 (4) 96 (2) vs 92 (3) 94 (2) vs 92 (3) 92 (3) vs 94 (4) pH PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 7.421 (0.043) vs 7.379 (0.046) 7.421 (0.043) vs 7.389 (0.040) 7.389 (0.040) vs 7.379 (0.046) 7.421 (0.043) vs 7.374 (0.040) 7.389 (0.040) vs 7.374 (0.040) 7.374 (0.040) vs 7.379 (0.046) PCO2 PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 43.9 (6.0) vs 50.7 (7.2) 43.9 (6.0) vs 47.8 (7.1) 47.8 (7.1) vs 50.7 (7.2) 43.9 (6.0) vs 50.3 (8.7) 47.8 (7.1) vs 50.3 (8.7) 50.3 (8.7) vs 50.7 (7.2) VT PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 0.453 (0.179) vs 0.322 (0.107) 0.453 (0.179) vs 0.384 (0.113) 0.384 (0.113) vs 0.322 (0.137) 0.453 (0.179) vs 0.295 (0.094) 0.384 (0.113) vs 0.295 (0.094) 0.295 (0.094) vs 0.322 (0.137) p value Adjusted p value 2 (1 to 4) 2 (0 to 3) 1 (-1 to 2) 5 (3 to 6) 3 (1 to 4) -2 (-4 to -1) 0.005 0.030 0.48 <0.001 0.001 0.004 0.02 NS NS <0.001 0.002 0.012 .039 (0.03 to 0.05) .026 (0.01 to 0.04) .013 (0 to 0.03) .047 (0.03 to 0.06) .021 (0.01 to 0.04) -0.01 (-0.02 to 0.01) <0.001 0.001 0.087 <0.001 0.012 0.33 <0.001 0.003 NS <0.001 0.048 NS -6.3 (-8.3 to -4.3) -3.4 (-5.4 to -1.4) -2.9 (-4.9 to -0.9) -6.8 (-8.9 to -4.7) -3.4 (-5.5 to -1.3) 0.4 (-1.7 to 2.5) <0.001 0.002 0.006 <0.001 0.003 0.68 0.001 0.006 0.030 <0.001 0.012 NS 0.130 (0.045 to 0.214) 0.068 (-0.014 to 0.150) 0.062 (-0.022 to 0.146) 0.158 (0.076 to 0.239) 0.089 (0.007 to 0.171) -0.027 (-0.112 to 0.057) 0.004 0.099 0.145 <0.001 0.034 0.511 0.008 NS NS <0.001 NS NS SpO2%: oxygen saturation; PCO2: arterialized venous carbon dioxide tension; VT: tidal volume (L); PS 20: pressure support 20 cmH2O; UnA: unassisted exercise; PS 10: pressure support 10 cmH2O; Sham: sham pressure support; Adjusted p: p value adjusted using a sharper Bonferroni correction [4]; NS: not significant Change from baseline to end exercise For the change from baseline to end exercise (where exercise endurance time varied between conditions), there was a difference between interventions with respect to RPE, SBP, DBP, MAP, pH, PCO2, La and RR (Table 6). Pairwise comparisons of the four interventions with a sharper Bonferroni [4] correction of p values, revealed that the change in RPE was greater with PS 20 compared to sham. Changes in blood pressure were greater with PS 20 and unassisted exercise compared to sham PS. Arterialised venous pH decreased to a greater extent with PS 20 during walking compared to unassisted exercise, sham PS and PS 10, and a greater increase in PCO2 was observed when PS 20 was used during exercise compared to unassisted exercise and sham PS. In addition, change in blood La was significantly higher with PS 20 compared to sham PS. Lastly, change in RR from rest to end of exercise was significantly lower with sham PS compared to unassisted exercise (Table 8). 5 Table 8 Pairwise comparisons of walking unassisted, with sham pressure support, pressure support 10 cmH2O and pressure support 20 cmH2O for perceived exertion, cardiovascular variables, pH, partial pressure of carbon dioxide, lactate and respiratory rate for the change from baseline to end exercise Comparison Mean change (SD) vs mean change (SD) Mean difference (95% CI) p value Adjusted p value RPE PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 6.4 (2.8) vs 5.7 (2.7) 6.4 (2.8) vs 4.8 (2.5) 4.8 (2.5) vs 5.7 (2.7) 6.4 (2.8) vs 4.4 (2.3) 4.8 (2.5) vs 4.4 (2.3) 4.4 (2.3) vs 5.7 (2.7) 0.7 (-0.8 to 2.1) 1.6 (0.2 to 3.1) -1.0 (-2.4 to 0.5) 2.0 (0.5 to 3.4) 0.3 (-1.1 to 1.8) -1.3 (-2.8 to 0.1) 0.38 0.035 0.20 0.011 0.64 0.084 NS NS NS 0.011 NS NS SBP PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 32.4 (17.0) vs 34.6 (25.6) 32.4 (17.0) vs 27.0 (16.4) 27.0 (16.4) vs 34.6 (25.6) 32.4 (17.0) vs 20.3 (19.8) 27.0 (16.4) vs 20.3 (19.8) 20.3 (19.8) vs 34.6 (25.6) -2.0 (-10.8 to 6.8) 5.4 (-3.2 to 14.0) -7.4 (-16.2 to 1.4) 12.1 (3.5 to 20.7) 6.7 (-1.9 to 15.3) -14.1 (-22.9 to -5.3) 0.66 0.23 0.108 0.009 0.135 0.003 NS NS NS 0.018 NS 0.003 DBP PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 8.0 (8.5) vs 3.9 (6.7) 8.0 (8.5) vs 2.8 (4.4) 2.8 (4.4) vs 3.9 (6.7) 8.0 (8.5) vs -3.8 (8.0) 2.8 (4.4) vs 3.8 (8.0) 3.8 (8.0) vs 3.9 (6.7) 4.1 (-1.2 to 9.4) 5.2 (-0.1 to 10 5) -1.2 (-6.4 to 4.1) 11.8 (6.5 to 17.1) 6.5 (1.3 to 11.8) -7.7 (-13.0 to -2.4) 0.139 0.060 0.67 <0.001 0.020 0.007 NS NS NS <0.001 NS 0.014 MAP PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 16.1 (10.1) vs 13.3 (12.0) 16.1 (10.1) vs 10.9 (7.9) 10.9 (7.9) vs 13.3 (12.0) 16.1 (10.1) vs 4.3 (10.4) 10.9 (7.9) vs 4.3 (10.4) 4.3 (10.4) vs 13.3 (12.0) 2.9 (-2.6 to 8.4) 5.3 (-0.2 to 10.8) -2.4 (-7.9 to 3.1) 11.9 (6.4 to 17.4) 6.6 (1.1 to 12.1) -9.0 (-14.5 to -3.5) 0.31 0.068 0.40 <0.001 0.024 0.003 NS NS NS <0.001 NS 0.006 pH PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA -0.059 (0.040) vs -0.024 (0.027) -0.059 (0.040) vs -0.033 (0.027) -0.033 (0.027) vs -0.024 (0.027) -0.059 (0.040) vs -0.015 (0.022) -0.033 (0.027) vs -0.015 (0.022) -0.015 (0.022) vs -0.024 (0.027) -0.04 (-0.05 to -0.02) -0.03 (-0.04 to -0.01) -0.01 (-0.03 to 0.01) -0.05 (-0.06 to -0.03) -0.02 (-0.04 to 0) 0.010 (-0.01 to 0.03) 0.001 0.008 0.34 <0.001 0.062 0.32 0.002 0.024 NS <0.001 NS NS PCO2 PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 7.2 (5.9) vs 3.1 (4.7) 7.2 (5.9) vs 5.8 (3.7) 5.8 (3.7) vs 3.1 (4.7) 7.2 (5.9) vs 2.5 (4.5) 5.8 (3.7) vs 2.5 (4.5) 2.5 (4.5) vs 3.1 (4.7) 4.1 (1.3 to 6.9) 1.5 (-1.3 to 4.3) 2.7 (-0.1 to 5.5) 4.3 (1.3 to 7.2) 2.8 (-0.1 to 5.8) -0.2 (-3.1 to 2.8) 0.005 0.30 0.062 0.006 0.060 0.91 0.005 NS NS 0.012 NS NS La PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 0.9 (0.7) vs 0.6 (0.6) 0.9 (0.7) vs 0.6 (0.4) 0.6 (0.4) vs 0.6 (0.6) 0.9 (0.7) vs 0.5 (0.4) 0.6 (0.4) vs 0.5 (0.4) 0.5 (0.4) vs 0.6 (0.6) 0.26 (-0.03 to 0.55) 0.25 (-0.04 to 0.55) 0.01 (-0.28 to 0.30) 0.46 (0.15 to 0.77) 0.21 (-0.10 to 0.51) -0.20 (-0.50 to 0.11) 0.087 0.097 0.96 0.006 0.20 0.22 NS NS NS 0.006 NS NS RR PS 20 vs UnA PS 20 vs PS 10 PS 10 vs UnA PS 20 vs Sham PS 10 vs Sham Sham vs UnA 14.8 (5.9) vs 17.8 (7.7) 14.8 (5.9) vs 13.9 (7.5) 13.9 (7.5) vs 17.8 (7.7) 14.8 (5.9) vs 11.0 (6.0) 13.9 (7.5) vs 11.0 (6.0) 11.0 (6.0) vs 17.8 (7.7) -3.1 (-7.4 to 1.2) 0.8 (-3.3 to 5.0) -3.9 (-8.2 to 0.3) 3.4 (-0.4 to 7.9) 2.9 (-1.2 to 7.1) -6.8 (-11.1 to 2.6) 0.17 0.70 0.081 0.086 0.18 0.004 NS NS NS NS NS 0.004 RPE: rate of perceived exertion (Borg); SBP: systolic blood pressure (mmHg); DBP: diastolic blood pressure (mmHg); MAP: mean arterial pressure (mmHg); PCO2: arterialized venous carbon dioxide tension; La: lactate (mmol/L); RR: respiratory rate; PS 20: pressure support 20 cmH2O, UnA: unassisted exercise; PS 10: pressure support 10 cmH2O; Sham: sham pressure support; Adjusted p: p value adjusted using a sharper Bonferroni correction[4]; NS: not significant 6 Subjective responses to pressure support during exercise A repeated measures ANOVA revealed a difference between exercise with sham PS, PS 10 and PS 20 with respect to VAS scores for the amount of “help” provided and “breathlessness” (p<0.001 and p<0.001 respectively, Figure 6). Pairwise comparisons are shown in Table 9. Figure 6 Visual analogue scales representing the effect of sham pressure support (PS), pressure support 10 cmH2O (PS 10) and pressure support 20 cmH2O (PS 20) on: a) “help during exercise”; b) “breathlessness during exercise”. Mean scores are presented and the whiskers represent standard deviation. Scores above the horizontal dashed line at 50% represent an advantage relative to unassisted walking, and scores below the dashed line represent a disadvantage relative to unassisted walking. *: p < 0.05; †: p < 0.01; ‡: p < 0.001 after the sharper Bonferroni correction[4]; * (light grey): p < 0.05 prior to the sharper Bonferroni correction [4] 7 Table 9 Pairwise comparisons of walking with sham pressure support, pressure support 10 cmH2O and pressure support 20 cmH2O for “help during exercise” and “breathlessness” Comparison Mean (SD) vs Mean (SD) Mean difference (95% CI) p value Adjusted p value Help during exercise PS 20 vs PS 10 PS 20 vs Sham PS 10 vs Sham 73.6 (21.0) vs 54.3 (24.4) 73.6 (21.0) vs 36.0 (22.0) 54.3 (24.4) vs 36.0 (22.0) 19.3 (2.7 to 35.9) 37.6 (25.7 to 49.5) 18..3 (3.5 to 33.0) 0.026 <0.001 0.019 NS <0.001 0.038 Breathlessness PS 20 vs PS 10 PS 20 vs Sham PS 10 vs Sham 74.7 (20.5) vs 64.8 (17.9) 74.7 (20.5) vs 40.9 (17.1) 64.8 (17.9) vs 40.9 (17.1) 9.8 (-2.1 to 21.8) 33.8 (19.4 to 48.1) 23.9 (10.4 to 37.4) 0.097 <0.001 0.002 NS <0.001 0.004 Data are presented as a percentage of the 10 cm visual analogue scale. Zero represents no help during exercise and no reduction in breathlessness. One hundred represents maximum help during exercise and maximum reduction in breathlessness. PS 20: pressure support 20 cmH2O; UnA: PS 10: pressure support 10 cmH2O; Sham: sham pressure support; Adjusted p: p value adjusted using a sharper Bonferroni correction [4]; NS: not significant References [1] Forster HV, Dempsey JA, Thomson J, Vidruk E, DoPico GA. Estimation of arterial PO2, PCO2, pH, and lactate from arterialized venous blood. Journal of Applied Physiology. 1972 Jan;32:134-7. [2] Morgan EJ, Baidwan B, Petty TL, Zwillich CW. The effects of unanesthetized arterial puncture on PCO2 and pH. American Review of Respiratory Disease. 1979 Oct;120:795-8. [3] Tang Y, Turner MJ, Yem JS, Baker AB. Calibration of pneumotachographs using a calibrated syringe. Journal of Applied Physiol. 2003;95:571-6. [4] Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988:800-2. 8