Mortality in COPD patients according to clinical phenotypes

Figures & data

Table 1 Clinical and demographic characteristics of the studied subjects, classified by phenotypes

Variable	Overall, N=891	(1) ACO, N=75 (8.4%)	(2) NONEX, N=531 (59.5%)	(3) EXCB, N=194 (21.7%)	(4) EXEMPH, N=91 (10.2%)	P-value**
Age (years)	69.5±9.4	68.0±9.0	68.5±9.5	72.7±8.9a	69.8±8.5	<0.001
Males, n (%)	721 (80.9)	38 (50.6)	433 (81.5)	167 (86.0)	78 (85.7)	<0.0001
Oxygen saturation (%)	93.2±4.4	94.8±2.5b	93.9±3.9b	91.8±4.9a	90.6±5.5a	<0.001
FEV1%	50.9±16.9	56.6±12.9a	53.6±16.8a	46.4±16.2c	39.8±15.5d	<0.001
FVC%	73.4±16.8	73.4±15.9	76.0±16.7b	67.5±15.4	70.7±17.1	<0.001
FEV1/FVC%	49.8±12.4	55.4±10.8e	50.9±11.8f	48.8±12.7f	40.4±12.0d	<0.001
GOLD 1, n (%)	44 (5.0)	3 (4.0)	38 (7.1)	3 (1.5)	1 (1.0)	<0.0001
GOLD 2, n (%)	412 (46.2)	51 (68.0)	268 (50.4)	66 (34.0)	26 (28.5)
GOLD 3, n (%)	326 (36.5)	20 (26.6)	184 (34.6)	91 (46.9)	31 (34.0)
GOLD 4, n (%)	109 (12.2)	1 (1.3)	41 (7.7)	34 (17.5)	33 (36.2)
BMI (kg/m^2)	28.4±5.3	29.9±4.9g	28.5±5.5	28.5±4.9	26.8±5.3	0.003
Charlson index*	1.9±1.3	1.4±0.9h	1.8±1.2h	2.2±1.5	2.0±1.4	<0.001
BODEX index	2.5±1.8	1.7±1.3b	2.0±1.5b	3.5±1.9c	4.3±2.1d	<0.001

Notes: Results are expressed as mean ± standard deviation or as number of cases (percentage).

* Nonage adjusted.

** P-value for comparisons between the four phenotypes. Pairwise comparisons:

a P<0.05 vs (1) and (2);

b P<0.05 vs (3) and (4);

c P<0.05 vs (1), (2), and (4);

d P<0.05 vs (1), (2), and (3);

e P<0.05 vs (2), (3), and (4);

f P<0.05 vs (1) and (4);

g P<0.05 vs (4); and

h P<0.05 vs (3).

Abbreviations: ACO, asthma–COPD overlap; BMI, body mass index; BODEX, BMI, obstruction, dyspnea, exacerbations index; EXCB, exacerbator with chronic bronchitis; EXEMPH, exacerbator with emphysema; GOLD, Global Initiative for Chronic Obstructive Lung Disease; NONEX, nonexacerbator.

Figure 1 Kaplan–Meier survival curves for the different phenotypes.

Abbreviations: ACO, asthma–COPD overlap; EXCB, exacerbator with chronic bronchitis; EXEMPH, exacerbator with emphysema; NONEX, nonexacerbator.

Table 2 Causes of death for the different phenotypes

Cause of death	Overall, N=891	ACO, N=75	NONEX, N=531	EXCB, N=194	EXEMPH, N=91	P-value*
COPD,a n (%)	66 (7.4)	2 (2.6)	23 (4.3)	21 (10.8)	20 (21.9)	<0.0001
Lung cancer, n (%)	20 (2.2)	0	13 (2.4)	3 (1.5)	4 (4.3)	0.24
Nonlung cancer, n (%)	27 (3.0)	1 (1.3)	18 (3.3)	6 (3.0)	2 (2.1)	0.75
CV, n (%)	25 (2.8)	4 (5.3)	15 (2.8)	4 (2.0)	2 (2.1)	0.51
Nonrespiratory sepsis, n (%)	6 (0.6)	0	3 (0.5)	2 (1.0)	1 (1.0)	0.74
Pneumonia or respiratory sepsis, n (%)	5 (0.5)	0	3 (0.5)	1 (0.5)	1 (1.0)	0.82
Renal failure, n (%)	2 (0.2)	0	0	1 (0.5)	1 (1.0)	0.15
Mesenteric ischemia, n (%)	2 (0.2)	0	0	2 (1.0)	0	0.06
Others, n (%)	7 (0.7)	1 (1.3)	5 (0.9)	0	1 (1.0)	0.55
Unknown, n (%)	34 (3.8)	1 (1.3)	17 (3.2)	13 (6.7)	3 (3.2)	0.09
Total, n (%)	194 (21.7)	9 (12)	97 (18.2)	53 (27.3)	35 (38.4)	<0.0001

Notes: Data are expressed as number (percentage of the whole population in each phenotype).

a Exacerbation or progression of the disease.

* P-value for comparisons between the four phenotypes.

Abbreviations: ACO, asthma–COPD overlap; CV, cardiovascular disease; EXCB, exacerbator with chronic bronchitis; EXEMPH, exacerbator with emphysema; NONEX, nonexacerbator.

Table 3 Results of the univariate and multivariate Cox proportional hazards analyses, using BODEX index

Variable	Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age	1.06 (1.04–1.08)	<0.0001	1.05 (1.03–1.07)	<0.0001
Male gender	2.57 (1.62–4.08)	0.0001	1.35 (0.81–2.25)	0.23
BODEX index	1.48 (1.38–1.57)	<0.0001	1.58 (1.45–1.72)	<0.0001
Charlson index	1.47 (1.36–1.58)	<0.0001	1.39 (1.38–1.52)	<0.0001
EXCBa	2.39 (1.18–4.85)	0.01	0.51 (0.24–1.09)	0.08
NONEXa	1.90 (1.01–3.76)	0.04	1.37 (0.67–2.80)	0.38
EXEMPHa	3.67 (1.76–7.63)	0.0005	0.78 (0.35–1.74)	0.55

Note:

a The ACO phenotype is the reference.

Abbreviations: ACO, asthma–COPD overlap; BMI, body mass index; BODEX, BMI, obstruction, dyspnea, exacerbations index; CI, confidence interval; EXCB, exacerbator with chronic bronchitis; EXEMPH, exacerbator with emphysema; HR, hazard ratio; NONEX, nonexacerbator.

Table 4 Results of the univariate and multivariate Cox proportional hazards analyses, using BMI, FEV₁%, and mMRC values

Variable	Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age	1.06 (1.04–1.08)	<0.0001	1.06 (1.03–1.09)	<0.0001
Male gender	2.57 (1.62–4.08)	0.0001	1.68 (0.87–3.22)	0.11
BMI	0.92 (0.89–0.95)	<0.0001	0.95 (0.91–0.99)	0.04
FEV1%	0.96 (0.95–0.97)	<0.0001	0.96 (0.94–0.98)	0.0001
mMRC values	2.10 (1.73–2.55)	<0.0001	1.50 (1.14–1.96)	0.003
Charlson index	1.47 (1.36–1.58)	<0.0001	1.39 (1.38–1.52)	<0.0001
EXCBa	2.39 (1.18–4.85)	0.01	0.34 (0.11–1.01)	0.054
NONEXa	1.90 (1.01–3.76)	0.04	0.82 (0.32–2.00)	0.69
EXEMPHa	3.67 (1.76–7.63)	0.0005	0.41 (0.12–1.36)	0.15

Note:

a The ACO phenotype is the reference.

Abbreviations: ACO, asthma–COPD overlap; BMI, body mass index; CI, confidence interval; EXCB, exacerbator with chronic bronchitis; EXEMPH, exacerbator with emphysema; HR, hazard ratio; mMRC, modified Medical Research Council; NONEX, nonexacerbator.