Co-morbidities and Hyperinflation Are Independent Risk Factors of All-cause Mortality in Very Severe COPD

Figures & data

Figure 1.  Patients´ recruitment.

Table 1.  Patients’ characteristics and association with mortality

Variable	n	Median (IQR)	HR*	95%-CI*	p-value*	p-value^#
Age (yr)	209	63.0 (56.0–69.0)	1.933	1.348–2.772	<0.001	<0.001
BMI (kg/m^2)	209	24.4 (20.8–28.9)	0.695	0.485–0.997	0.041	0.007
Sex (f/m)	209	58/151 (27.8/72.2)	0.850	0.561–1.288	0.455	0.372
Hb (g/dl)	209	13.8 (12.8–14.8)	0.681	0.476–0.973	0.031	0.605
Hc (%)	209	41.0 (38.0–44.0)	0.605	0.424–0.865	0.005	0.298
Leukocytes (×103/μl)	209	9.0 (7.3–11.5)	1.546	1.078–2.218	0.014	0.118
Creatinine (mg/dl)	209	0.88 (0.70–1.00)	0.983	0.688–1.406	0.925	0.769
GFR (ml/min/1.73m^2)	209	88.0 (71.7–97.0)	0.959	0.670–1.372	0.815	0.485
FEV1 (l)	209	0.70 (0.58–0.81)	0.714	0.495–1.031	0.058	0.580
FEV1 (%predicted)	209	25.0 (22.0–26.9)	0.749	0.521–1.077	0.106	0.799
FEV1 / FVC (%)	209	44.0 (39.0–49.0)	1.019	0.708–1.467	0.918	0.686
TLC (l)	202	7.97 (7.07–9.17)	1.257	0.875–1.806	0.209	0.148
TLC (%predicted)	202	130.8 (116.4–144.9)	1.085	0.750–1.570	0.545	0.981
RV (l)	202	6.16 (5.26–7.17)	1.637	1.138–2.355	0.007	0.075
RV (%predicted)	202	272.9 (237.8–311.5)	1.211	0.842–1.742	0.290	0.458
RV / TLC (%)	202	76.84 (72.21–81.67)	2.095	1.445–3.038	<0.001	0.013
RV / TLC (%predicted)	202	197.9 (184.8–210.5)	1.060	0.737–1.523	0.750	0.346
IC / TLC	202	0.162 (0.125–0.204)	0.717	0.499–1.031	0.068	0.761
mMRC	186	3.0 (2.0–3.0)	1.727	1.146–2.603	0.017	0.093
6-MWD (m)	125	279.0 (210.0–346.5)	0.681	0.412–1.125	0.099	0.624
6-MWD (%predicted)	125	51.0 (38.6–62.6)	0.709	0.429–1.172	0.141	0.844

*For mortality from any cause, using the median as cut-off value.

^#For mortality from respiratory cause, using the median as cut-off value.

Definition of abbreviations: BMI = body-mass-Index; Hb = hemoglobin; Hc = hematocrit; GFR = glomerular filtration rate; VC = vital capacity; FEV₁ = forced expiratory volume in 1 second; SRtot = specific airway resistance; ITGV = intrathoracic gas volume; TLC = total lung capacity; RV = residual volume; IC = inspiratory capacity; MMRC = modified medical research council; 6-MWD = 6-minute walk distance.

Table 2.  Co-morbidities and association with mortality

Co-morbidities	n	(%)	HR*	95%-CI*	p-value*	p-value#
Cardiovascular risk factors
Systemic hypertension	113	54.1	1.169	0.819–1.671	0.385	0.756
Hyperlipidemia	80	38.3	0.988	0.691–1.411	0.945	0.510
Diabetes mellitus	41	19.6	1.200	0.764–1.885	0.398	0.832
Cardiac diseases (any of following)	94	45.0	1.511	1.053–2.170	0.020	0.025
Coronary artery disease	35	16.7	1.054	0.640–1.735	0.833	0.249
Left-heart failure	39	18.7	1.415	0.903–2.213	0.090	0.004
Atrial fibrillation	34	16.3	1.551	0.905–2.657	0.056	0.222
Malignancies	24	11.5	1.795	0.959–3.358	0.019	0.236
Depression/anxiety	55	26.3	1.203	0.784–1.846	0.368	0.178
Chronic renal failure§	27	12.9	1.413	0.788–2.535	0.177	0.654
Anemia (Hb < 12/13 g/dl (f/m))	48	23.0	1.335	0.849–2.101	0.165	0.288
Obesity (BMI ≥ 30 kg/m^2)	43	20.6	0.562	0.372–0.849	0.018	0.055
Underweight (BMI < 18.5 kg/m^2)	22	10.5	2.385	1.002–5.679	0.003	0.006

*For mortality from any cause.

^#For mortality from respiratory cause.

^§GFR < 60 ml/min

Definition of abbreviations: HR = hazard ratio; CI = confidence interval; GFR = glomerular filtration rate; Hb = hemoglobin; BMI = body-mass-index.

Figure 2a. Distribution of points of the COTE-index either < (light grey column) or ≥ (dark grey columns) the median value (1.0 (0.0–3.0)).

Table 3.  Combined scores and the risk of mortality

Variable	n	Median (IQR)	HR*	95%-CI*	p-value*	p-value#
BODE	125	7.0 (5.0–7.0)	1.818	1.092–3.027	0.010	0.344
BOD	186	5.0 (5.0–6.0)	1.506	0.987–2.299	0.036	0.106
ADO	186	6.0 (5.0–7.0)	2.218	1.506–3.265	<0.001	<0.001
COTE Index	209	1.0 (0.0–3.0)	1.911	1.338–2.730	<0.001	0.016
Age-COTE Index	209	3.0 (2.0–5.0)	1.992	1.395–2.847	<0.001	0.008
Charlson Index	209	2.0 (1.0–3.0)	1.852	1.297–2.644	<0.001	0.016
Age-Charlson Index	209	4.0 (3.0–5.0)	2.163	1.514–3.089	<0.001	0.002

*For mortality from any cause, using the median as cut-off value.

^#For mortality from respiratory cause, using the median as cut-off value.

Figure 2b. Distribution of points of the age-COTE-index either < (light grey column) or ≥ (dark grey columns) the median value (3.0 (2.0–53.0)).

Figure 3a. Kaplan-Meier curve of RV/TLC either < (grey line, group 0) or ≥ (black line, group 1) the median value (76.84%; HR 2.095 (1.445–3.038), p < 0.001) regarding all-cause mortality.

Figure 3b. Kaplan-Meier curve of FEV₁%predicted either < (black line, group 0) or ≥ (grey line, group 1) the median value (25.0%; HR 0.749 (0.521–1.077), p = 0.106) regarding all-cause mortality.

Figure 3c. Kaplan-Meier curve of the COTE-index either < (grey line, group 0) or ≥ (black line, group 1) the median value (1.0; HR 1.911 (1.338–2.730), p < 0.001) regarding all-cause mortality.

Figure 3d. Kaplan-Meier curve of the Charlson-index either < (grey line, group 0) or ≥ (black line, group 1) the median value (2.0; HR 1.852 (1.297–2.644), p < 0.001) regarding all-cause mortality.

Table 4a.  Multivariate analysis for death from any cause using the respective median

Variable	HR	95%-CI	p-value
BMI (kg/m^2)	0.781	0.535–1.140	0.200
Age (yrs)	1.424	0.946–2.142	0.090
Sex (f/m)	0.785	0.478–1.290	0.340
RV/TLC (%)	2.005	1. 318–3.051	0.001
COTE Index	1.720	1.139–2.597	0.010

Table 4b.  Multivariate analysis for death from respiratory cause using the respective median

Variable	HR	95%-CI	p-value
BMI (kg/m^2)	0.575	0.344–0.962	0.035
Age (yrs)	2.136	1.208–3.778	0.009
Sex (f/m)	0.816	0.415–1.601	0.554
RV/TLC (%)	1.487	0.866–2.552	0.150
COTE Index	1.552	0.901–2.675	0.113

Definition of abbreviations: HR = hazard ratio; CI = confidence interval; BMI = body mass-index; RV/TLC = residual volume to total lung capacity; COTE = COPD specific co-morbidity test.