Acute exacerbation of COPD during pulmonary rehabilitation: outcomes and risk prediction

Figures & data

Table 1 Baseline characteristics of 125 patients at the beginning of the PRP

Subject characteristics	EX group (n=32)	NEX group (n=93)	P-value
Stages completed	27/32 (84.4)	90/93 (96.8)	0.01
Age, years	66.4±7.3	64.5±8.7	0.26
Sex: male/female	14/18	57/36	0.09
Current smoking	10/22 (31.3)	18/75 (19.4)	0.17
Regular use of oxygen	21/11 (65.6)	24/69 (25.8)	0.0001
Charlson score	4.2±2.2	3.8±1.6	0.23
Pulmonary medication use
No medication	2 (6.2)	3 (3.2)	0.37
1 medication (LABA or LAMA)	0 (0.0)	6 (6.5)
2 medications (LABA and LAMA or LABA and ICS)	11 (34.4)	37 (39.8)
3 medications (LABA, LAMA, and ICS)	19 (59.4)	47 (50.5)
FVC, % pred	71.8±21.7	78.0±23.0	0.19
FEV1, % pred	39.7±19.6	48.6±20.3	0.033
FEV1/FVC	41.5±10.3	50.3±13.1	0.001
COPD classification according to the severity of airflow limitation (GOLD stages 1–4)
1	2 (6.9)	9 (9.7)	0.01
2	3 (9.4)	33 (35.5)
3	20 (62.5)	30 (32.3)
4	7 (21.2)	21 (22.5)
COPD classification according to symptoms, breathlessness, spirometric classification, and risk of exacerbations (GOLD stages A–D)
A	0 (0.0)	1 (1.1)	0.153
B	4 (12.5)	29 (31.2)
C	0 (0.0)	1 (1.1)
D	28 (87.5)	62 (66.6)
BODE index	5.6±2.2	3.4±2.0	<0.001
BMI, kg/m^2	22.9±4.8	26.6±6.5	0.003
6MWT, m	309±101	376±88	0.001
VO2 peak, mL/kg/min	11.7±3.5	13.4±3.8	0.06
WR peak, W	41.6±17.2	64.0±24.3	<0.001
mMRC score	2.9±0.8	2.1±0.9	<0.001
HADS score	15.1±6.4	16.0±6.1	0.53
CAT score	22.8±5.5	19.6±6.6	0.03
VSRQ score	31.5±15.2	36.4±12.8	0.10

Notes: The patients were allocated into two groups according to the occurrence (EX group) or not (NEX group) of a COPD exacerbation. Data are presented as n (%) or mean ± SD except sex, which is presented as n.

Abbreviations: 6MWT, 6-minute walk test; BMI, body mass index; BODE, body mass index, airway obstruction, dyspnea, exercise capacity; CAT, COPD assessment test; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HADS, Hospital Anxiety and Depression Scale; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; % pred, percent predicted; PRP, pulmonary rehabilitation program; VO₂ peak, peak oxygen uptake; VSRQ, visual simplified respiratory questionnaire; WR peak, peak work rate.

Figure 1 Flowchart of patients who were enrolled in the study.

Abbreviations: AECOPD, acute exacerbation of COPD; PRP, pulmonary rehabilitation program.

Table 2 Outcomes of PR in 117 completed stages according to the occurrence (EX group) or nonoccurrence (NEX group) of a COPD exacerbation

Variable	EX group (n=27)		NEX group (n=90)		P-value
	Before PR	After PR	Before PR	After PR	Between patients (grouping variable: exacerbation)	Within patients (repeated measure)	Interaction of factors
BODE index	5.4±2.3	4.2±1.9	3.3±1.9	2.3±1.8	<0.001	<0.001	0.460
FVC, % pred	75.2±19.1	74.1±17.9	78.8±22.6	81.9±22.6	0.246	0.499	0.048
FEV1, % pred	41.9±19.9	41.2±18.7	49.0±20.1	51.0±21.2	0.068	0.696	0.064
6MWT, m	320±101	354±101	379±85	442±97	<0.001	<0.001	0.019
VO2 peak, mL/kg/min	11.9±3.4	13.6±4.7	13.5±3.8	14.8±5.4	0.421	0.013	0.860
WR peak, W	42.1±17.9	56.7±20.1	64.0±23.5	75.4±28.3	0.001	<0.001	0.512
mMRC score	2.9±0.8	2.0±0.9	2.0±0.9	1.4±0.8	<0.001	<0.001	0.176
HADS score	16.0±6.2	12.6±5.7	15.0±6.5	11.3±6.0	0.305	<0.001	0.712
CAT score	23.0±5.4	21.0±6.0	19.6±6.6	15.4±6.6	<0.001	<0.001	0.111
VSRQ score	31.2±15.4	39.3±14.8	36.6±12.7	49.7±14.2	0.004	<0.001	0.093

Note: Data are presented as mean ± SD.

Abbreviations: 6MWT, 6-minute walk test; BODE index, body mass index, airway obstruction, dyspnea, exercise capacity; CAT, COPD Assessment Test; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; % pred, percent predicted; PR, pulmonary rehabilitation; VO₂ peak, peak oxygen uptake; VSRQ, visual simplified respiratory questionnaire; WR peak, peak work rate.

Table 3 Characteristics of 32 AECOPD episodes

Occurrence of AECOPD after enrolment in PRP, days	12.8 (10.1–15.6)a
Duration of medical intervention, days	8.2 (6.8–9.5)a
Positivity of sputum sample	9 (28.1)b
Courses of corticosteroids	25 (78.1)
Courses of antibiotics	26 (81.3)
Severity of AECOPDc
Mild	10 (31.3)
Moderate	16 (50.0)
Severe	6 (18.7)

Notes: Data are presented as mean (CI), mean ± SD, or n (%).

a Nonnormal distribution.

b Haemophilus influenzae, n=4; Staphylococcus aureus, n=2; Streptococcus pneumoniae, n=1; Escherichia coli, n=1; Pseudomonas aeruginosa, n=1.

c See definitions in text.

Abbreviations: AECOPD, acute exacerbation of COPD; PRP, pulmonary rehabilitation program.

Table 4 Sensitivity, specificity, optimal threshold value, and AUC for the BODE, DOSE, SCOPEX indices, and NEXA as predictors of the occurrence of an AECOPD during pulmonary rehabilitation

	Sensitivity (95% CI)	Specificity (95% CI)	Optimal threshold value	AUC (95% CI)	P-value
BODE index	78.1 (60.0–90.7)	73.6 (64.1–81.7)	>4	0.776 (0.692–0.845)	<0.0001
DOSE index	21.9 (9.3–40.0)	87.1 (78.5–93.2)	>4	0.504 (0.413–0.594)	0.952
SCOPEX index	84.4 (67.2–94.7)	51.6 (41.0–62.1)	>39	0.738 (0.652–0.813)	<0.0001
NEXA	56.3 (37.7–40.0)	66.7 (56.1–76.1)	>1	0.632 (0.541–0.717)	0.02

Abbreviations: AECOPD, acute exacerbation of COPD; AUC, area under the receiver operating characteristics curve; BODE, body mass index, airway obstruction, dyspnea, exercise capacity; DOSE, dyspnea, obstruction, smoking, exacerbation; NEXA, number of AECOPD episodes in the year preceding enrolment; SCOPEX, score to predict short-term risk of COPD exacerbations.

Figure 2 Receiver operating characteristic curves of three multidimensional indices predicting the occurrence of an exacerbation during pulmonary rehabilitation and of NEXA at their optimal threshold value.

Note: Red dotted line: line of identity.
Abbreviations: AECOPD, acute exacerbation of COPD; BODE1, BODE index at baseline; BODE, body mass index, airway obstruction, dyspnea, exercise capacity; DOSE, dyspnea, obstruction, smoking, exacerbation; NEXA, number of AECOPD episodes in the year preceding enrolment; SCOPEX, score to predict short-term risk of COPD exacerbations.