Pulmonary rehabilitation for COPD improves exercise time rather than exercise tolerance: effects and mechanisms

Figures & data

Figure 1 Exercise time (T_ex)/Δ oxygen uptake $\left({\dot{\mathrm{V}}\mathrm{O}}_2\right)$, that is, time–slope.

Note: The T_ex standardized by the increase of ${\dot{\mathrm{V}}\mathrm{O}}_2$ from resting to peak exercise during cardiopulmonary exercise testing.

Figure 2 The effects of PR on peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ and T_ex.

Note: All patients are classified into four groups by whether the exercise time (T_ex) or the peak oxygen uptake $\left({\dot{\mathrm{V}}\mathrm{O}}_2\right)$ did or did not increase after PR.
Abbreviation: PR, pulmonary rehabilitation.

Figure 3 Study flow diagram.

Abbreviations: CPET, cardiopulmonary exercise testing; PR, pulmonary rehabilitation.

Table 1 Baseline patient characteristics (n=36)

Age, years	69.0±8.4 (53–83)
Sex, male/female	35/1
Weight, kg	52.5±10.7 (34.7–88.0)
BMI, kg⋅m^−2	20.2±3.7 (14.7–33.5)
GOLD stage, I/II/III/IV	1/1/20/14
Pulmonary function
FEV1, L	0.90±0.37 (0.42–2.34)
%FEV1, % predicted	34.5±13.9 (15.5–89.7)
FEV1/FVC, %	40.6±9.8 (18.7–65.2)
VC, L	2.77±0.61 (1.47–3.98)
%VC, %	87.0±16.8 (45.9–115.9)
Incremental CPET
Exercise time, sec	437±177 (170–776)
Peak ${\dot{\mathrm{V}}\mathrm{O}}_2$, mL⋅kg^−1⋅min^−1	13.8±3.9 (8.1–22.2)
Medications
LAMA	12
SAMA	10
LABA	7
SABA	7
ICS	6
Methylxanthines	21

Notes: Data are presented as mean ± SD (range) unless otherwise stated. Medications are not mutually exclusive, and data are presented separately.

Abbreviations: BMI, body mass index; CPET, cardiopulmonary exercise testing; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroids; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; VC, vital capacity; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake.

Table 2 Patient characteristics of the two groups before pulmonary rehabilitation

	Time only-increased group (n=18)	Two factors-increased group (n=11)	P-value between groups
Age, years	69.7±7.9	71.6±7.7	0.357
BMI, kg⋅m^−2	20.6±2.9	21.0±5.0	0.964
GOLD stage, I/II/III/IV	0/1/12/5	1/0/6/4	0.463
Pulmonary function
FEV1, L	0.93±0.32	0.94±0.50	0.406
%FEV1, % predicted	35.4±11.5	37.6±19.3	0.653
FEV1/FVC, %	39.7±9.5	44.8±10.9	0.291
VC, L	2.83±0.65	2.70±0.59	0.445
%VC, %	88.1±17.6	87.6±17.7	0.653
CPET with BGA, at peak exercise
${\dot{\mathrm{V}}\mathrm{O}}_2$, mL⋅min^−1⋅kg^−1	14.8±3.7	14.2±3.4	0.707
pH	7.351±0.040	7.344±0.052	0.702
PaO2, mmHg	63.3±13.1	63.6±11.4	0.964
PaCO2, mmHg	43.7±6.4	43.2±6.6	0.857
Plasma lactate, mg⋅dL^−1	34.7±12.4	35.3±13.6	0.963

Notes: Data are presented as mean ± SD (range) unless otherwise stated. In the time only increased group, exercise time was increased, but the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ was economized after pulmonary rehabilitation; in the two factors increased group, both the exercise time and the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ were increased after pulmonary rehabilitation.

Abbreviations: BGA, blood gas analyses; BMI, body mass index; CPET, cardiopulmonary exercise testing; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; PaCO₂, arterial carbon dioxide tension; PaO₂, arterial oxygen tension; VC, vital capacity; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake.

Table 3 Changes in incremental exercise parameters at peak exercise after pulmonary rehabilitation

	Time only-increased group (n=18)		Two factors-increased group (n=11)		P-value between groups
	Pre-PR	Difference	Pre-PR	Difference
Dyspnea, Borg scale	6.6±2.2	−1.3±2.2*	6.5±2.7	−1.7±1.8*	0.663
${\dot{\mathrm{V}}\mathrm{O}}_2$, mL⋅min^−1	739±213	−65±39****	730±208	82±52***	<0.0001
Exercise time, sec	421±173	72±71***	465±171	124±57****	0.050
Time–slope, sec⋅mL^−1⋅min	0.93±0.33	0.28±0.22****	0.94±0.14	0.07±0.15	0.011
F, breaths⋅min^−1	30.3±5.8	−1.2±6.9	30.1±4.5	−0.9±6.2	0.903
VT, mL	1,072±297	29±169	1,086±322	164±160**	0.043
${\dot{\mathrm{V}}}_{\mathrm{E}}$, L⋅min^−1	31.4±7.4	−0.7±2.8	32.6±11.2	3.6±4.6*	0.004
${\dot{\mathrm{V}}\text{CO}}_2$, mL⋅min^−1	768±260	−69±56****	773±273	114±73***	<0.0001
R	1.03±0.12	0.00±0.06	1.04±0.10	0.03±0.05	0.182
VD/VT	0.35±0.06	0.01±0.05	0.35±0.08	−0.02±0.04	0.137
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\mathrm{O}}_2$	43.4±5.2	3.6±4.3**	44.8±9.5	−0.1±4.5	0.034
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\text{CO}}_2$	43.0±7.7	3.5±4.4**	43.0±8.0	−1.4±4.2	0.006
ΔFO2, %	2.88±0.35	−0.31±0.25****	2.82±0.55	0.17±0.33	0.0002
Ti/Ttot	35.3±7.4	2.7±5.2*	38.5±5.6	0.5±4.0	0.228
HR, beats⋅min^−1	121.1±19.4	1.4±17.3	120.3±19.2	5.5±11.7	0.504
${\dot{\mathrm{V}}\mathrm{O}}_2$/HR, mL⋅beats^−1	6.2±1.7	−0.7±0.4****	6.0±1.0	0.4±0.5*	<0.0001
SpO2, %	90.2±5.9	−0.5±3.4	90.6±4.7	−0.9±3.9	0.779

Notes: Data are presented as mean ± SD. The data of 33 patients were obtained from CPET performed under room air conditions, that is, FiO₂ =21%. The FiO₂ of two patients was 24%, and the FiO₂ of one patient was 30%.

* P<0.05,

** P<0.01,

*** P<0.001,

**** P<0.001. The post-PR results were compared with the pre-PR results within each group. In the time only increased group, exercise time was increased, but the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ was economized after pulmonary rehabilitation; in the two factors increased group, both the exercise time and the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ were increased after pulmonary rehabilitation.

Abbreviations: ΔFO₂, the inspired oxygen concentration (FiO₂) minus expired oxygen concentration (FeO₂); F, breathing frequency; HR, heart rate; R, gas exchange ratio; SpO₂, oxygen saturation; T_i/T_tot, the ratio of inspiratory time to total breathing cycle time; time–slope, exercise time/ $\mathrm{\Delta }{\dot{\mathrm{V}}\mathrm{O}}_2$; ${\dot{\mathrm{V}}\text{CO}}_2$, carbon dioxide output; V_D/V_T, physiologic dead space/tidal volume ratio; ${\dot{\mathrm{V}}}_{\mathrm{E}}$, minute ventilation; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake; V_T, tidal volume.

Table 4 Changes in incremental exercise parameters at iso-time after pulmonary rehabilitation

	Time only-increased group (n=18)		Two factors-increased group (n=11)		P-value between groups
	Pre-PR	Difference	Pre-PR	Difference
Dyspnea, Borg scale	6.6±2.2	−2.5±2.2***	6.5±2.7	−3.6±2.1***	0.181
${\dot{\mathrm{V}}\mathrm{O}}_2$, mL⋅min^−1	739±213	−102±46****	730±208	−3±44	<0.0001
F, breaths⋅min^−1	30.3±5.8	−2.8±6.8	30.1±4.5	−3.5±6.2	0.761
VT, mL	1,072±297	32±172	1,086±322	155±161**	0.067
${\dot{\mathrm{V}}}_{\mathrm{E}}$, L⋅min^−1	31.4±7.4	−2.3±2.5**	32.6±11.2	−0.4±3.4	0.082
${\dot{\mathrm{V}}\text{CO}}_2$, mL⋅min^−1	768±260	−117±73****	773±273	3±78	0.0003
VD/VT	0.35±0.06	0.02±0.04	0.35±0.08	−0.01±0.04	0.108
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\mathrm{O}}_2$	43.4±5.2	3.5±4.2**	44.8±9.5	−0.0±4.6	0.047
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\text{CO}}_2$	43.0±7.7	4.0±4.4**	43.0±8.0	−0.2±4.2	0.017
ΔFO2, %	2.88±0.35	−0.28±0.25***	2.82±0.55	0.04±0.32	0.006
Ti/Ttot	35.3±7.4	2.5±4.3*	38.5±5.6	0.5±4.8	0.246
HR, beats⋅min^−1	121.1±19.4	−3.2±18.1	120.3±19.2	−3.4±13.2	0.973
${\dot{\mathrm{V}}\mathrm{O}}_2$/HR, mL⋅beats^−1	6.2±1.7	−0.7±0.5****	6.0±1.0	0.2±0.8	0.0007
SpO2, %	90.2±5.9	0.5±4.0	90.6±4.7	0.6±3.5	0.969

Notes: Data are presented as mean ± SD. The data of 33 patients were obtained from CPET performed under room air conditions, that is, FiO₂ =21%. The FiO₂ of two patients was 24%, and the FiO₂ of one patient was 30%.

* P<0.05,

** P< 0.01,

*** P<0.001,

**** P<0.001. The post-PR results were compared with the pre-PR results within each group. In the time only increased group, exercise time was increased, but the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$ was economized after pulmonary rehabilitation; in the two factors increased group, both the exercise time and the peak ${\dot{\mathrm{V}}\mathrm{O}}_2$, were increased after pulmonary rehabilitation.

Abbreviations: ΔFO₂, the inspired oxygen concentration (FiO₂) minus expired oxygen concentration (FeO₂); F, breathing frequency; HR, heart rate; SpO₂ oxygen saturation; T_i/T_tot, the ratio of inspiratory time to total breathing cycle time; ${\dot{\mathrm{V}}\text{CO}}_2$, carbon dioxide output; V_D/V_T, physiologic dead space/tidal volume ratio; ${\dot{\mathrm{V}}}_{\mathrm{E}}$, minute ventilation; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake; V_T, tidal volume.

Figure 4 The changes of exercise variables before and after pulmonary rehabilitation.

Notes: In the time only increased group, the data for peak exercise in 18 patients and the data for AT, which were obtained at both pre- and post-PR, in 12 patients were used. In the two factors increased group, the data for peak exercise in 11 patients and the data for AT, which were obtained at both pre- and post-PR, in 10 patients were used. The post-PR results are compared with the pre-PR results within each group (*P<0.05, **P<0.01, ***P<0.001, ****P<0.001) and between the two groups (^#P<0.05, ^##P<0.01, ^###P<0.001, ^####P<0.001) using paired t-tests and unpaired t-tests, respectively.
Abbreviations: AT, anaerobic threshold; ΔFO₂, the inspired oxygen concentration (FiO₂) minus expired oxygen concentration (FeO₂); peak ex., peak exercise; ${\dot{\mathrm{V}}\text{CO}}_2$, carbon dioxide output; ${\dot{\mathrm{V}}}_{\mathrm{E}}$, minute ventilation; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake.

Table 5 Correlations between baseline variables and the change ratio of the time–slope at post-PR to the time–slope at pre-PR (n=36)

	R	P-value
Age, years	0.039	0.823
BMI, kg⋅m^−2	0.496	0.002
Pulmonary function
FEV1, L	0.032	0.855
CPET
Dyspnea, at peak ex., Borg scale	−0.103	0.551
Exercise time, at peak ex., sec	−0.171	0.320
${\dot{\mathrm{V}}\mathrm{O}}_2$, at peak ex., mL⋅min^−1	0.158	0.359
Time–slope, sec⋅mL^−1⋅min	−0.496	0.002
${\dot{\mathrm{V}}\text{CO}}_2$, at peak ex., mL⋅min^−1	0.120	0.488
F, at peak ex., breaths⋅min	0.037	0.829
VT, at peak ex., mL	0.076	0.663
${\dot{\mathrm{V}}}_{\mathrm{E}}$, at peak ex., L⋅min^−1	−0.026	0.880
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\mathrm{O}}_2$, at peak ex.	−0.348	0.037
${\dot{\mathrm{V}}}_{\mathrm{E}}$/ ${\dot{\mathrm{V}}\text{CO}}_2$, at peak ex.	−0.267	0.117
VD/VT, at peak ex.	−0.256	0.132
${\dot{\mathrm{V}}\mathrm{O}}_2$/HR, mL⋅beats^−1	0.270	0.111
pH, at peak ex.	−0.170	0.325
PaO2, at peak ex., mmHg	0.224	0.190
PaCO2, at peak ex., mmHg	−0.007	0.967
Plasma lactate, at peak ex., mg⋅dL^−1	0.063	0.721

Abbreviations: At peak ex., at peak exercise; BMI, body mass index; CPET, cardiopulmonary exercise testing; F, breathing frequency; FEV₁, forced expiratory volume in 1 s; HR, heart rate; PaCO₂, arterial carbon dioxide tension; PaO₂, arterial oxygen tension; time–slope, exercise time/ $\mathrm{\Delta }{\dot{\mathrm{V}}\mathrm{O}}_2$; VC, vital capacity; ${\dot{\mathrm{V}}\text{CO}}_2$, carbon dioxide output; V_D/V_T physiologic dead space/tidal volume ratio; ${\dot{\mathrm{V}}}_{\mathrm{E}}$, minute ventilation; ${\dot{\mathrm{V}}\mathrm{O}}_2$, oxygen uptake; V_T, tidal volume.

Figure 5 Correlation between the ratio of the post-to-pre-change ratio of the time–slope and the baseline time–slope.

Abbreviation: PR, pulmonary rehabilitation.