Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

Figures & data

Table 1 Characteristics, laboratory findings, and pulmonary function tests of study groups

	Healthy control (n=30)	AE-COPD (n=43)	P-value
Age, years, mean (SD)	64 (7)	68 (8)	0.346a
Sex, male (n, %)	25 (83)	40 (93)	0.260b
BMI, kg/m^2, mean (SD)	28.9 (4.8)	27.4 (4.6)	0.410a
Ever-smoker (n, %)	27 (90)	41 (95)	0.332b
Current smoker (n, %)	10 (33)	10 (23)	0.748b
Cigarettes (pack-years)	40 (17)	53 (20)	0.059c
COPD duration (years), mean (SD)	NA	8.3 (4.2)	NA
Predicted FEV1%	NA	37 (12)	NA
Predicted FEV1/FVC	NA	51 (10)	NA
Stage of disease (n, %)
I	NA	0 (0)	NA
II		8 (19)
III		24 (55)
IV		11 (26)
Arterial blood gases, mean (SD)
pH	NA	7.38 (0.05)	NA
PO2(mmHg)		57 (8)
PCO2(mmHg)		43 (9)
Patients with inhaled corticosteroids (n, %)	NA	43 (100)	NA
Patients with LABA (n, %)	NA	43 (100)	NA

Notes: Data are median (interquartile) unless otherwise indicated.

a Independent-samples t-test.

b Fisher’s exact test.

c Mann–Whitney U-test.

Abbreviations: AE-COPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; CRP, C-reactive protein; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LABA, long-acting beta agonist; NA, not applicable; PO₂, partial pressure of oxygen; PCO₂, partial pressure of carbon dioxide; SD, standard deviation.

Figure 1 Serum soluble urokinase-type plasminogen activator receptor (suPAR) in healthy controls and in patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) on the first and seventh days.

Notes: Data are expressed as boxplots, in which the horizontal lines illustrate the 25th, 50th, and 75th percentiles of the values of suPAR. The vertical lines represent the 5th and 95th percentiles.

Figure 2 Serum soluble urokinase-type plasminogen activator receptor (suPAR) during an acute exacerbation and on the seventh day of treatment.

Notes: Median circulating suPAR during an acute exacerbation was 4.84±1.90 ng/mL, compared to 3.38±1.34 ng/mL (P<0.001) on the seventh day of treatment.

Figure 3 Serum suPAR and FEV₁ % of predicted in patients with acute exacerbation of chronic obstructive pulmonary disease.

Notes: Serum suPAR was correlated inversely with FEV₁% of predicted using Pearson correlation (r=−478, P=0.001).
Abbreviations: FEV₁, forced expiratory volume in 1 second; ln, natural log-transformed; suPAR, soluble urokinase-type plasminogen activator receptor.

Figure 4 C-reactive protein (CRP) (A) and fibrinogen (B) in healthy subjects and patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) on the first and the seventh day.

Note: Box and whisker plots represent medians, interquartile ranges, and range.

Figure 5 Serum C-reactive protein (CRP) (A) and fibrinogen (B) during an acute exacerbation and on the seventh day of the treatment.

Notes: Median circulating CRP and fibrinogen during an acute exacerbation were 4.25±6.26 mg/dL and 577±226 mg/dL, compared to 2.54±4.18 mg/dL (P<0.001) and 420±190 mg/dL (P<0.001) on the seventh day of treatment, respectively.

Table 2 Pearson correlation coefficients of suPAR with inflammatory markers in patients with AE-COPD on the first and seventh day

Variable	suPARa (ng/dL)
	Patients with AE-COPD
	First day	(P-value)	Seventh day	(P-value)
CRPa	0.331	0.030	0.301	0.049
Fibrinogen	0.585	P<0.001	0.426	0.004
Sedimentationa	0.218	0.159	0.071	0.652
Leukocytea	0.094	0.549	0.102	0.514

Note:

a Variables were natural log-transformed. Bold text indicates this value is statistically significant and less than <0.05.

Abbreviations: AE-COPD, acute exacerbation of chronic obstructive pulmonary disease; CRP, C-reactive protein; suPAR, serum soluble urokinase-type plasminogen activator receptor.

Figure 6 ROC curve for suPAR, CRP, and fibrinogen in discrimination of patients with acute exacerbation of chronic obstructive pulmonary disease on the first and seventh day.

Abbreviations: CRP, C-reactive protein; ROC, receiver operating characteristic; suPAR, soluble urokinase-type plasminogen activator receptor.

Table 3 Univariate and multivariate logistic regression analysis of inflammatory markers in patients with acute exacerbation of chronic obstructive pulmonary disease as the dependent variable

Analysis	β	SE	P-value	OR (95% CI for β)
Univariate
suPARa	112.841	1.115	<0.001	12.869–1,003.487
Fibrinogen	1.007	0.002	<0.001	1.003–1.012
CRPa	2.229	0.263	0.002	1.332–3.728
Multivariate
suPARa	64.391	1.316	0.002	4.882–849.342
Fibrinogen	1.005	0.002	0.014	1.001–1.010
CRPa	1.022	0.061	0.720	0.907–1.151

Note:

a Variable was natural transformed. Bold text indicates this value is statistically significant and less than <0.05.

Abbreviations: CI, confidence interval; CRP, C-reactive protein; OR, odds ratio; suPAR, soluble urokinase-type plasminogen activator recepto; SE, standard error.