Predicting Mortality in COPD with Validated and Sensitive Biomarkers; Fibrinogen and Mid-Range-Proadrenomedullin (MR-proADM)

Figures & data

Figure 1. Study design of the COMIC study.

Table 1. Baseline characteristics.

	Stable state N = 640	AECOPD N = 262
Mean age at enrollment in years (SD)	67 (9)	71 (9.6)
Male, N (%)	384 (60)	156 (60)
Smoking status, N (%)
Current smokers	166 (26)	78 (30)
Lung function (post-bronchodilator)
Mean FEV1 in liters (SD)	1.46 (0.61)	1.30 (0.54)
Mean FEV1 as % of predicted (SD)	54 (19)	49 (18)
Mean FEV1/VC in % of predicted (SD)	45 (14)	43 (14)
GOLD classification 2005, N (%)
I	59 (9)	17 (6)
II	288 (45)	94 (36)
III	240 (38)	122 (47)
IV	53 (8)	29 (11)
Mean BMI at enrollment (SD)^a	27 (5.0)	27 (5.7)
Mean mMRC (0-4) (SD)^b	1.7 (1.2)	2.1 (1.3)
Mean ADO-score (SD)^c	4.0 (1.8)	4.9 (1.8)
Comorbidity, N (%)
Heart failure	109 (17)	49 (19)
Myocardial infarction	26 (4)	17 (7)

a BMI is missing of respectively 12 and 0 patients at stable state and at AECOPD.

b mMRC-score is missing of respectively 17 and 10 patients at stable state and at AECOPD.

c ADO-score is missing of respectively 17 and 10 patients at stable state and at AECOPD.

Abbreviations; AECOPD: Acute exacerbation of COPD; N: Number; SD: Standard Deviation; BMI: Body Mass Index; FEV₁: Forced Expiratory Volume in 1 s; GOLD: Global Initiative for Chronic Obstructive Lung disease; mMRC: modified Medical Research Council dyspnea grade; ADO: Index that combines Age, Dyspnea (mMRC) and airflow Obstruction (FEV1% predicted).

Table 2. Fibrinogen.

	Fibrinogen g/l (Median [IQR])
Stable state
Non-survivors* (N = 134)	4.6 [3.9–5.4]
Survivors (N = 506)	4.1 [3.6–4.7]
Difference between groups	p < 0.001
AECOPD
Non-survivors* (N = 80)	5.4 [4.3–6.4]
Survivors (N = 182)	5.2 [4.3–6.4]
Difference between groups	p = 0.606

* Died within follow-up period of three years.

Abbreviations; AECOPD: Acute exacerbation of COPD; N: Number; IQR: Inter quartile range.

Figure 2. Scatterplot of fibrinogen versus MR-proADM levels in stable state.

Table 3. Survival analysis.

	HR	95% CI	p-value	cHR*	95% CI	p-value	C-statistic
Fibrinogen *	4.03	2.40-6.76	p < 0.001	2.39	1.41–4.05	p < 0.001	0.73
MR-proADM *	2.76	2.06-3.69	p < 0.001	2.22	1.59–3.10	p < 0.001	0.75
Fibrinogen and MR-proADM *
Fibrinogen *	3.18	1.85-5.45	p < 0.001	2.17	1.27–3.70	p < 0.01	0.76
MR-proADM *	2.46	1.83-3.32	p < 0.001	2.12	1.51–2.96	p < 0.001

* Measured in stable state and corrected for age, sex, GOLD status and BMI (12 missing BMI, total number of patients 628).

Abbreviations; HR: Hazard Ratio; CI: Confidence Interval; cHR: Corrected Hazard Ratio.

Figure 3. ROC curves for prediction of death after 1 year.

Abbreviations; ROC: Receiver Operating Characteristic

Table 4. Logistic regression analysis for death after one year.

Variable	cOR*	cOR 95% CI	AUC	AUC 95% CI
Fibrinogen*	4.80	1.80–12.81	0.78	0.74–0.81
MR-proADM*	3.84	2.03–7.27	0.82	0.78–0.86
Fibrinogen & MR-proADM*	4.39	1.60–12.05	0.83	0.80–0.86
	3.59	1.90–6.78

* Measured in stable state and corrected for age, sex, GOLD status and BMI (12 missing BMI, total number of patients 628).

Abbreviations; cOR: Corrected Odds Ratio; CI: Confidence Interval; AUC: Area Under the Curve.