A comparison of three multidimensional indices of COPD severity as predictors of future exacerbations

Figures & data

Figure 1 Flow chart for patient selection.

Abbreviations: COPD, chronic obstructive pulmonary disease; DOSE, dyspnea, obstruction, smoking, exacerbations.

Table 1 Baseline characteristics of patients with COPD according to the occurrence of exacerbation during a 1-year period

Characteristic	Total	With exacerbation	Without exacerbation	P-value
Gender, M/F	170/13	62/2	108/11	0.105
Age (y)	71.4 ± 8.7	72.5 ± 9.1	70.8 ± 8.5	0.229
FEV1 (L)	1.50 ± 0.64	1.27 ± 0.66	1.63 ± 0.61	<0.001
FEV1% predicted (%)	55.7 ± 20.7	47.8 ± 18.1	59.9 ± 20.9	<0.001
%DLco/VA (%)	59.2 ± 22.8	53.9 ± 20.3	62.0 ± 23.5	0.002
LTOT use (%)	40.4	62.5	37.5	<0.001
PaO2 (torr)	80.1 ± 12.1	82.6 ± 14.1	79.9 ± 10.9	0.166
PaCO2 (torr)	41.9 ± 5.2	42.8 ± 5.1	41.4 ± 5.3	0.113
Current smoking (%)	4.4	4.7	4.2	0.575
Smoking pack-years	75.6 ± 45.3	82.1 ± 47.1	72.1 ± 44.1	0.159
GOLD stage I/II/III/IV (n)	25/78/62/18	6/17/31/10	19/61/31/8	0.001
BMI (kg/m^2)	22.2 ± 3.1	21.9 ± 2.5	22.4 ± 3.4	0.235
FFMI (kg/m^2)	17.0 ± 1.7	16.7 ± 1.4	17.1 ± 1.8	0.116
6MWD (m)	464.1 ± 111.9	436.7 ± 107.1	478.6 ± 112.1	0.016
MMRC dyspnea scale	1.3 ± 1.0	1.6 ± 1.0	1.1 ± 0.9	0.001
LAA%	34.1 ± 14.8	38.7 ± 14.4	31.6 ± 14.5	0.002
WA%	53.9 ± 12.5	55.4 ± 11.5	53.1 ± 13.0	0.237
Charlson index	2.6 ± 1.0	2.6 ± 0.9	2.6 ± 1.0	0.84
BODE index	2.4 ± 2.2	3.1 ± 2.2	2.1 ± 2.1	0.001
ADO index	4.0 ± 1.7	4.5 ± 1.7	3.7 ± 1.6	0.001
DOSE index	1.3 ± 1.4	2.1 ± 1.5	0.9 ± 1.2	<0.001
Previous exacerbation rate	0.57 ± 0.98	1.13 ± 1.28	0.28 ± 0.58	<0.001

Note: Data are expressed as means ± SD except where otherwise noted.

Abbreviations: 6MWD, 6-minute walking distance; ADO, age/dyspnea/airflow obstruction; BMI, body mass index; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; COPD, chronic obstructive pulmonary disease; DLco/VA, diffusing capacity of the lung for carbon monoxide and alveolar volume ratio; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; FEV₁, forced expiratory volume in 1 second; FFMI, fat-free mass index; GOLD, Global initiative for chronic Obstructive Lung Disease; LAA%, percentage of low-attenuation area; LTOT, long-term oxygen therapy; MMRC, Modified Medical Research Council dyspnea scale; Previous exacerbation, exacerbation of COPD within the previous year; SD, standard deviation; WA%, percentage of airway wall area.

Table 2 Univariate analysis of predictors of COPD exacerbation

Variable	Odds ratio	95% CI	P-value
Age	1.03	0.99–1.06	0.160
Previous exacerbation	2.79	1.85–4.21	<0.001
GOLD stage	2.00	1.35–2.96	0.001
BODE index	1.26	1.09–1.45	0.002
ADO index	1.36	1.11–1.64	0.002
DOSE index	1.90	1.48–2.43	<0.001
MMRC	1.72	1.24–2.40	0.001
6MWD	0.99	0.94–0.99	0.018
BMI	0.94	0.85–1.04	0.235
FFMI	0.86	0.71–1.04	0.118
LAA%	1.03	1.01–1.06	0.003
FEV1% predicted	0.97	0.95–0.99	<0.001
%DLco/VA	0.98	0.97–0.99	0.023
LTOT use	4.17	2.19–7.93	<0.001
PaO2	1.02	0.99–1.05	0.170
PaCO2	1.05	0.99–1.12	0.119
Charlson index	0.97	0.71–1.33	0.846

Abbreviations: 6MWD, 6-minute walking distance; 95% CI, 95% confidence interval; ADO, age/dyspnea/airflow obstruction; BMI, body mass index; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; COPD, chronic obstructive pulmonary disease; DLco/VA, diffusing capacity of the lung for carbon monoxide and alveolar volume ratio; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; FFMI, fat-free mass index; GOLD, Global initiative for chronic Obstructive Lung Disease; LAA%, percentage of low-attenuation area; LTOT, long-term oxygen therapy; MMRC, Modified Medical Research Council dyspnea scale; Previous exacerbation, COPD exacerbation within the previous year; FEV₁, forced expiratory volume in 1 second.

Figure 2 Receiver-operator curves for the multidimensional grading systems, GOLD stage, and previous exacerbation rate as predictors of the occurrence of exacerbation during the 1-year follow-up.

Notes: The AUC and the 95% CI are shown for each index. The AUC for the DOSE index is significantly larger than for the other multidimensional assessments or GOLD stage (P < 0.001), but shows no difference versus previous exacerbation rate (P = 0.40).
Abbreviations: AUC, area under the curve; ADO, age/dyspnea/airflow; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; CI, confidence interval; DOSE, dyspnea, obstruction, smoking, exacerbations GOLD, Global initiative for chronic Obstructive Lung Disease.

Table 3 Adjusted multivariate logistic regression analysis of predictors of COPD exacerbation

Model	Variable	Odds ratio	95% CI	P-value
Model I: GOLD	MMRC	1.81	1.26–2.59	0.001
	Previous AE	2.98	1.92–4.65	<0.001
Model II: BODE	LTOT use	2.92	1.45–5.87	0.003
	Previous AE	2.57	1.67–3.96	<0.001
Model III: ADO	ADO index	1.40	1.13–1.73	0.002
	Previous AE	2.92	1.89–4.52	<0.001
Model IV: DOSE	DOSE index	2.19	1.52–3.14	<0.001
	LTOT use	2.37	1.12–5.01	0.024

Notes: Model I: included all of the variables selected in the univariate analyses except for the BODE, ADO, and DOSE indices. Model II: included the BODE index and replaced GOLD stage, MMRC, and 6MWD. Model III: included the ADO index and 6MWD and replaced the BODE index. Model IV: included the DOSE index and replaced the ADO index and exacerbation of COPD within the previous year.

Abbreviations: 95% CI, 95% confidence interval; ADO, age/dyspnea/airflow obstruction; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; COPD, chronic obstructive pulmonary disease; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; GOLD, Global initiative for chronic Obstructive Lung Disease; LTOT, long-term oxygen therapy; MMRC, Modified Medical Research Council dyspnea scale; Previous AE, COPD exacerbation within the previous year.

Table 4 Correlations between the multidimensional assessment systems or previous exacerbation rate and markers of disease severity

Variable	BODE index		ADO index		DOSE index		Previous exacerbation rate
	ρ	P-value	ρ	P-value	ρ	P-value	ρ	P-value
BMI	−0.491	<0.001	−0.275	<0.001	−0.328	<0.001	−0.165	0.026
FFMI	−0.514	<0.001	−0.420	<0.001	−0.371	<0.001	−0.125	0.110
6MWD	−0.669	<0.001	−0.752	<0.001	−0.608	<0.001	−0.024	0.749
PaO2	−0.194	0.012	−0.209	0.007	−0.188	0.015	0.014	0.855
PaCO2	0.353	<0.001	0.258	0.001	0.313	<0.001	0.036	0.644
%DLco/VA	−0.403	<0.001	−0.267	<0.001	−0.335	<0.001	−0.104	0.162
LAA%	0.570	<0.001	0.372	<0.001	0.485	<0.001	0.161	0.030
WA%	−0.320	0.689	−0.320	0.693	0.000	0.998	0.052	0.693

Abbreviations: ρ, Spearman’s rank correlation coefficient; 6MWD, 6-min walking distance; ADO, age/dyspnea/airflow obstruction; BMI, body mass index; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; DLco/VA, diffusing capacity of the lung for carbon monoxide and alveolar volume ratio; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; FFMI, fat-free mass index; GOLD, Global initiative for chronic Obstructive Lung Disease; LAA%, percentage of low-attenuation area; WA%, percentage of wall area.

Figure S1 Sample diary used in the present study.

Figure S2 Distributions of GOLD stages and total numbers of patients according to the scores of each multidimensional grading system. (A) BODE index; (B) ADO index; (C) DOSE index.

Abbreviations: ADO, age/dyspnea/airflow obstruction; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; GOLD, Global initiative for chronic Obstructive Lung Disease.

Table S1 Patient responses to 88 exacerbations reported in the second year of the study period

Patient’s response	Number (%)
No visit or no additional medication	9 (10.2)
Medication taken based on patient’s self-assessment	19 (21.6)
Action plan used	18
Over-the-counter treatment	1
Visit to the RCC	24 (27.3)
Direct visit to the RCC	16
Visit to the RCC after taking medication on self-judgment	7
Visit to the RCC after visiting another clinic	1
Visit to another clinic or hospital	20 (22.7)
Direct visit to another clinic or hospital	18
Visit to another clinic or hospital after taking medicine on self-assessment	2
Hospitalization	16 (18.2)
After visiting another clinic or hospital	5
After visiting the RCC	2
Not known how patient was admitted	9

Abbreviation: RCC, respiratory care clinic.

Table S2 C-statistics for the multidimensional grading systems, GOLD stage, and previous exacerbation rate as predictors of an exacerbation during the 1-year follow-up (excluding six patients who did not receive medical intervention)

	AUC (95% confidence interval)	P-value
GOLD stage	0.66 (0.57–0.74)	0.001
BODE index	0.64 (0.55–0.72)	0.004
ADO index	0.64 (0.55–0.73)	0.003
DOSE index	0.75 (0.67–0.82)	<0.001
Previous exacerbation ratea	0.73 (0.64–0.82)	<0.001

Note:

a Exacerbation of chronic obstructive pulmonary disease within the previous year.

Abbreviations: ADO, age/dyspnea/airflow obstruction; AUC, area under the curve; BODE, body mass index/airflow obstruction/dyspnea/exercise capacity; DOSE, dyspnea/airflow obstruction/smoking status/exacerbation frequency; GOLD, Global initiative for chronic Obstructive Lung Disease.