Survival after pulmonary rehabilitation in patients with COPD: impact of functional exercise capacity and its changes

Figures & data

Table 1 Baseline characteristics of subjects

Demographic characteristics	All subjects	Completed 3 months of PR			Groups according to 6MWDi and ∆6MWD				P-value
		Yes	No	P-value	6MWDi ≥350 m		6MWDi <350 m
					∆≥30 m; Group 1	∆<30 m; Group 2	∆≥30 m; Group 3	∆<30 m; Group 4
Number of patients	423	333	90		125	144	74	80
Age (years)	65±8	66±8	65±8	0.7118	65±8	65±8	67±8	67±8	0.2380
Male sex, n (%)	335 (79)	265 (80)	70 (78)	0.7087	97 (77)	115 (80)	60 (81)	63 (79)	0.9400
BMI (kg·m^−2)	25±6	25±5	25±7	0.7913	26±5	26±5	24±6	25±6	0.5474
Lung function
FEV1 (% predicted)	43±16	43±15	44±19	0.8367	46±16	47±16	37±12*,†	37±16*,†	<0.0001
FEV1/FVC (%)	41±12	40±11	43±15	0.1643	42±11	42±11	37±11*,†	39±15	0.0066
FRC (% predicted)	154±37	154±37	152±38	0.5906	152±35	150±34	166±40*,†	153±39	0.0275
DLCO (% predicted)	48±17	48±18	48±18	0.8556	53±17	52±17	41±13*,†	40±17*,†	<0.0001
Peripheral muscle force
QF (Nm)	100±38	102±37	92±38	0.0232	113±35	110±35	79±30*,†	80±35*,†	<0.0001
QF (% predicted)	69±26	69±23	66±36	0.4644	75±21	78±28	57±23*,†	58±25*,†	<0.0001
Exercise capacity
Oxygen uptake (% predicted)	48±19	49±19	44±18	0.0245	53±18	51±18	40±18*,†	42±21*,†	<0.0001
Oxygen uptake (mL·kg·min^−1)	14±4	14±4	13±4*	0.0038	16±4	15±5	12±4*,†	11±3*,†	<0.0001
Max workload (% predicted)	48±20	49±19	45±20	0.0892	55±19	53±18	37±18*,†	37±16*,†	<0.0001
6MWD (m)	381±134	395±129	328±138	<0.0001	458±65	469±74	234±78*,†	230±84*,†	<0.0001
6MWD (% predicted)	59±21	61±20	52±22	<0.0001	71±10	73±11	37±13*,†	37±14*,†	<0.0001
Health-related quality of life
CRDQ dyspnea (points)	15±5	16±5	15±5	0.4908	16±5	16±5	14±5*	15±5	0.0161
CRDQ total score	78±17	78±17	76±17	0.1916	81±16	79±17	74±17*	73±16*	0.0026
Comorbidities
Cardiovascular (n, %)	313 (74)	246 (74)	67 (75)	0.8535	68 (85)	59 (79)	94 (66)	92 (74)	0.0124
Metabolic (n, %)	62 (15)	42 (13)	20 (23)	0.0209	12 (10)	17 (12)	14 (19)	19 (24)	0.0225
Musculoskeletal (n, %)	87 (21)	71 (22)	16 (18)	0.4730	23 (19)	17 (12)	26 (35)	21 (26)	0.0005
Mental health (n, %)	125 (30)	94 (28)	31 (35)	0.2387	35 (28)	34 (24)	27 (36)	29 (36)	0.1299
Hospital admissions in the first year
Time to first respiratory hospitalization (days)	129±97	99±88	138±99	0.0280	176±97	122±103	128±89	103±90*	0.0129
Hospitalizations within PR (n, %)	72 (17)	49 (14)	23 (25)	0.0152	8 (6)	24 (17)	16 (22)	24 (30)	0.0001
Hospitalizations in the first year (n, %)	161 (38)	121 (36)	40 (44)	0.1598	32 (25)	48 (33)	36 (48)	45 (56)	<0.0001

Notes: Data shown as mean ± SD, n (%), or P-value. Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; and Group 4: 6MWDi <350 m and Δ6MWD <30 m. P-values of the four groups refer to one-way analysis of variance or Kruskal–Wallis test;

* P<0.05 in post hoc test versus 1;

† P<0.05 in post hoc test versus 2. Bold font denotes statistical significance (P<0.05).

Abbreviations: 6MWD, 6-minute walk distance; 6MWDi, initial 6MWD; BMI, body mass index; CRDQ, chronic respiratory disease questionnaire; DL_co, diffusion capacity for carbon monoxide; FEV₁, forced expiratory volume in the first second; FRC, functional residual capacity; FVC, forced vital capacity; max, maximum; PR, pulmonary rehabilitation; QF, quadriceps force; SD, standard deviation.

Figure 1 Flow chart of patients’ inclusion.

Abbreviations: COPD, chronic obstructive pulmonary disease; PR, pulmonary rehabilitation.

Table 2 Exercise training responses

Outcomes	All subjects (n=333)	6MWDi ≥350 m		6MWDi <350 m
		∆≥30 m; Group 1 (n=125)	∆<30 m; Group 2 (n=98)	∆≥30 m; Group 3 (n=74)	∆<30 m; Group 4 (n=36)
Peripheral muscle force
ΔQF (Nm)	10 (0–22)*	11 (0–21)*	7 (−2–21)*	15 (4–29)*,‡	7 (−2–15)*
ΔQF (% from baseline)	10 (0–25)*	8 (0–20)*	5 (−2–21)*	16 (6–46)*,‡	11 (−2–24)*
Exercise capacity
ΔOxygen uptake (% from baseline)	8 (−5–21)*	11 (−4–24)*	2 (−6–16)*	14 (0–24)*,‡	−4 (−17–0)*,†,§
ΔMax workload (% from baseline)	14 (0–30)*	16 (0–28)*,§	11 (0–21)*	22 (0–50)*,†,‡	0 (0–25)†,§
Δ6MWD (m)	43 (12–78)*	59 (45–91)*	0 (−26–17)†	86 (54–136)*,†,‡	−8 (−62–18)*,†,§
Δ6MWD (% from baseline)	10 (3–23)*	13 (9–21)*	0 (−5–3)†	39 (23–67)*,†,‡	−3 (−24–6)*,†,§
Health-related quality of life
ΔCRDQ dyspnea	5 (2–8)*	6 (3–9)*	3 (1–8)*,†	6 (2–8)*	3 (0–6)*,†,§
ΔCRDQ total score	15 (8–24)*	17 (11–25)*	12 (4–22)*,†	16 (11–24)*	13 (2–22)*

Notes: Data shown as median (IQR). Data was only analyzed for subjects with data at both baseline and 3 months. Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; and Group 4: 6MWDi <350 m and Δ6MWD <30 m.

* P<0.05 for changes from baseline.

† Post hoc test versus 1;

‡ post hoc test versus 2;

§ post hoc test versus 3.

Abbreviations: Δ, difference (3 months − baseline); 6MWD, 6-minute walk distance; 6MWDi, initial 6MWD; CRDQ, chronic respiratory disease questionnaire; IQR, interquartile range; max, maximum; QF, quadriceps force.

Figure 2 Kaplan–Meier mortality curves for Groups 1–4.

Notes: Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; and Group 4: 6MWDi <350 m and Δ6MWD <30 m.
Abbreviations: 6MWD, 6-minute walk distance; 6MWDi, initial 6MWD.

Table 3 Mortality risks estimates using univariate and multivariate regression analysis on possible mortality confounders

Confounders	Univariate analysis; HR (95% CI)	P-value	Multivariate analysis; adjusted HR (95% CI)	P-value
BMI <21 kg·m^−2	1.36 (1.02–1.80)	0.0327	–	–
Presence of two or more comorbidities	1.24 (1.05–1.47)	0.0114	–	–
Age (per 5 years of increase)	1.16 (1.07–1.25)	0.0001	1.18 (1.06–1.31)	0.0017
Quadriceps force, as function of weight (per 10 units of increase)	0.97 (0.94–0.99)	0.0217	–	–
FEV1, % predicted (per 10 units of increase)	0.82 (0.75–0.89)	<0.0001	–	–
Oxygen uptake, % predicted (per 10 units of increase)	0.79 (0.73–0.85)	<0.0001	0.80 (0.72–0.89)	0.0010
DLCO, % predicted (per 10 units of increase)	0.78 (0.71–0.85)	<0.0001	–	–
Change in FEV1, % predicted after training (per unit of increase)	0.98 (0.96–0.99)	0.0080	0.98 (0.96–0.99)	0.0258
Change in quadriceps force after training (per 10 units of increase)	0.90 (0.84–0.98)	0.0139	0.90 (0.82–0.99)	0.0326
Change in BMI after training, per unit of increase	0.88 (0.78–0.99)	0.0391	–	–
Change in oxygen uptake, % predicted after training (per 10 units of increase)	0.85 (0.76–0.94)	0.0026	0.83 (0.70–0.98)	<0.0001
Change in Wmax after training (per 10 units of increase)	0.79 (0.70–0.88)	<0.0001	–	–
Change in 6MWD ≥30 m	0.66 (0.51–0.85)	0.0013	0.68 (0.49–0.94)	0.0214
Enrolling in the maintenance program (months 3–6)	0.62 (0.44–0.86)	0.0052	–	–
Initial 6MWD ≥350 m	0.39 (0.30–0.50)	<0.0001	0.46 (0.32–0.65)	<0.0001

Notes: Only variables that remained in the model are reported in the multivariate regression analysis. Bold font denotes statistical significance (P<0.05). –, indicates that the variable was not included in the multivariate model.

Abbreviations: 6MWD, 6-minute walk distance; BMI, body mass index; CI, confidence interval; DL_co, diffusion capacity for carbon monoxide; FEV₁, forced expiratory volume in the first second; HR, hazard ratio; W_max, maximal workload during cycling exercise test.

Table 4 Mortality risk estimates in the four groups adjusted by confounders

Adjusted risk compared to G1	HR adjusted (95% CI)	P-value
G4: <350 m and delta <30 m	3.28 (2.02–5.33)	<0.0001
G3: <350 m and delta ≥30 m	1.90 (1.28–2.84)	0.0016
G2: ≥350 m and delta <30 m	1.36 (0.92–2.00)	0.1144

Notes: G1, Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; G2, Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; G3, Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; G4, Group 4: 6MWDi <350 m and Δ6MWD <30 m. Bold font denotes statistical significance (P<0.05).

Abbreviations: 6MWD, 6-minute walk distance; 6MWDi, initial 6MWD; CI, confidence interval; HR, hazard ratio.