Prediction of short term re-exacerbation in patients with acute exacerbation of chronic obstructive pulmonary disease

Figures & data

Table 1 Characteristics of the patients according to whether they had re-exacerbation

	Re-exacerbation or death in 90 days
	No N=90	Yes N=86	P-value
Age in years, median (IQR)	70 (64, 75)	73 (66, 79)	0.044
Male, n (%)	71 (78.9)	73 (84.9)	0.303
BMI, mean ± SD	22.7±3.5	22.1±3.1	0.686
Smoking history, n (%)	63 (70.0)	66 (76.7)	0.312
AE frequency in the previous year, median (IQR)	2 (2, 3)	2.5 (2, 3)	0.036
Dyspnea mMRC, mean ± SD*	1.6±0.8	1.8±0.9	0.313
CAT, mean ± SD*	13.7±6.9	14.9±7.1	0.231
FEV1 %, median (IQR)*	38.3 (31.8, 50.4)	32.4 (24.5, 63.4)	0.150
GOLD stages, n (%)*
1	8 (8.9)	13 (15.1)	0.003
2	16 (17.8)	13 (15.1)
3	47 (52.2)	24 (28.0)
4	19 (21.1)	36 (41.9)
Use of accessory respiratory muscles, n (%)#	21 (23.3)	33 (38.4)	0.031
Presence of pleural effusion, n (%)#	1 (1.1)	8 (9.3)	0.016
Use of noninvasive mechanical ventilation, n (%)#	20 (22.2)	32 (37.2)	0.029
Use of controlled oxygen therapy, n (%)#	70 (77.8)	80 (93.0)	0.004
Use of ICS, n (%)$	69 (76.7)	51 (59.3)	0.013
Use of inhaled LABA, n (%)$	69 (76.7)	50 (58.1)	0.009
Length of hospital stay, n (%)	10 (8, 14)	12 (8, 15)	0.049
CODEX, median (IQR)	4 (3, 5)	4 (3, 6)	0.102
Re-AE INDEX, median (IQR)	7 (5, 8)	9 (7, 10)	0.000

Notes:

* In stable COPD.

# In the current AE.

$ Before discharge.

Abbreviations: BMI, body mass index; AE, acute exacerbation; mMRC, modified Medical Research Council; CAT, COPD assessment test; FEV₁%, forced expiratory volume in 1 second percent of predicted; GOLD, Global initiative for chronic Obstructive Lung Disease; ICS, inhaled corticosteroids; LABA, long-acting β-2-agonists; CODEX, comorbidity, obstruction, dyspnea, and previous severe exacerbations; Re-AE INDEX, re-exacerbation index; IQR, interquartile range; SD, standard deviation.

Table 2 Risk of re-exacerbation by univariate logistic regression analysis

Index (N=176)	95% CI	OR	P-value
Age grades	1.028–1.796	1.359	0.031
Sex	0.691–3.270	1.503	0.305
BMI	0.864–1.096	0.973	0.652
GOLD grades*	0.828–1.524	1.123	0.456
AE frequency in the previous year	1.026–2.704	1.665	0.039
FEV1%*	0.988–1.013	1.000	0.949
Presence of pleural effusion#	1.117–74.614	9.128	0.039
Use of noninvasive mechanical ventilation#	1.070–4.021	2.074	0.031
Use of controlled oxygen therapy#	1.448–10.020	3.810	0.007
Use of ICS$	0.231–0.850	0.443	0.014
Use of inhaled LABA$	0.221–0.809	0.423	0.009
Length of hospital stay (days) grades	1.214–2.941	1.890	0.005
CODEX	0.966–1.363	1.147	0.118
Re-AE INDEX	1.308–1.805	1.536	0.000

Notes:

* In stable COPD.

# In the current AE.

$ Before discharge.

Abbreviations: CI, confidence interval; OR, odds ratio; BMI, body mass index; GOLD, Global initiative for chronic Obstructive Lung Disease; AE, acute exacerbation; FEV₁%, forced expiratory volume in 1 second percent of predicted; ICS, inhaled corticosteroids; LABA, long-acting β-2-agonists; CODEX, comorbidity, obstruction, dyspnea, and previous severe exacerbations; Re-AE INDEX, re-exacerbation index.

Table 3 Variables and point values used for the computation of the re-AE INDEX

Variable	Points in re-AE INDEX
	−1	0	1	2	3
Age grades (years)	–	<65	65–70	71–77	>77
GOLD grades*	–	1	2	3	4
AE frequency in the previous year	–	0	1–2	≥3	–
Presence of pleural effusion#,&	–	No	–	Yes	–
Use of accessory respiratory muscles#	–	No	Yes	–	–
Use of noninvasive mechanical ventilation#	–	No	Yes	–	–
Use of controlled oxygen therapy#,&	–	No	–	Yes	–
Use of ICS$	Yes	No	–	–	–
Use of inhaled LABA$	Yes	No	–	–	–
Length of hospital stay (days)	–	≤10	11–20	21–30	>30

Notes:

* In stable COPD.

# In the current AE.

& Variable was weighted.

$ Before discharge.

Abbreviations: Re-AE INDEX, re-exacerbation index; GOLD, Global initiative for chronic Obstructive Lung Disease; AE, acute exacerbation; ICS, inhaled corticosteroids; LABA, long-acting β-2-agonists.

Table 4 Risk of re-exacerbation for re-AE INDEX by multivariate logistic regression analysis

Index	95% CI	OR	P-value
Re-AE INDEX*	1.339–1.902	1.596	0.000
Re-AE INDEX#	1.378–2.027	1.672	0.000
Re-AE INDEX&	1.389–2.101	1.709	0.000

Notes:

* Adjusted by age, sex, and smoking history.

# Adjusted by age, sex, smoking history, CAT, and mMRC.

& Adjusted by age, sex, smoking history, CAT, mMRC, and Charlson index.

Abbreviations: Re-AE INDEX, re-exacerbation index; CI, confidence interval; OR, odds ratio; CAT, COPD assessment test; mMRC, modified Medical Research Council.

Figure 1 The relationship between the rate of re-exacerbation and the re-AE INDEX scores.

Notes: Patients were divided into three groups depending upon the tertile of the re-AE INDEX score, and the re-exacerbation rate was compared among groups.
Abbreviation: Re-AE INDEX, re-exacerbation index.

Table 5 Comparison of predictive capacity of re-exacerbation among indexes and single variables by C-statistics

Parameters	C	SE	P-value	95% CI
Re-AE INDEX	0.750	0.036	0.000	0.678–0.821
CODEX	0.570	0.043	0.107	0.485–0.655
CAT*	0.554	0.044	0.215	0.469–0.639
mMRC*	0.547	0.044	0.279	0.462–0.633
GOLD grades*	0.555	0.044	0.205	0.468–0.642
FEV1 %*	0.437	0.045	0.150	0.349–0.525

Note:

* In stable COPD.

Abbreviations: SE, standard error; CI, confidence interval; Re-AE INDEX, re-exacerbation index; CODEX, comorbidity, obstruction, dyspnea, and previous severe exacerbations; CAT, COPD assessment test; mMRC, modified Medical Research Council; GOLD, Global initiative for chronic Obstructive Lung Disease; FEV₁%, forced expiratory volume in 1 second percent of predicted.

Figure 2 ROC curves for the re-AE INDEX, CODEX, GOLD grades, mMRC, CAT, and FEV₁%.

Notes: Risk of re-exacerbation strongly increased with increasing score of re-AE INDEX in the cohort. CODEX, CAT, mMRC, GOLD stages, or FEV₁% could not predict the outcome of re-exacerbation in 90 days after discharge efficiently.
Abbreviations: ROC, receiver operating characteristic; Re-AE INDEX, re-exacerbation index; CODEX, comorbidity, obstruction, dyspnea, and previous severe exacerbations; GOLD, Global initiative for chronic Obstructive Lung Disease in stable COPD; mMRC, modified Medical Research Council scale in stable COPD; CAT, COPD assessment test in stable COPD; FEV₁%, forced expiratory volume in 1 second percent of predicted in stable COPD.