Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD

Figures & data

Table 1 Clinical character of included subjects

Variable	Healthy controls (n=57)		COPD (n=101)		P-value
	Never smoker (n=37)	Smoker (n=20)	Never smoker (n=23)	Smoker (n=78)
Age, years	59.59±13.96	59.25±12.37	64.17±9.59	63.08±8.78	0.187
Sex, male/female	13/24	20/0	8/15	75/3	<0.001^a
BMI, kg/m^2	25.87±3.78	24.02±3.17	23.84±3.36^a	23.1±3.18^b	0.001^a
Smoking status					0.542
Ex-smoker (%)		13 (65)		52 (66.7)
Current smoker (%)		7 (35)		26 (33.3)
Pack-years for ever-smokers		44.36±32.13		38±26.27	0.36
Frequent exacerbator (≥2 exacerbations per year) (%)			9 (39.1)	16 (20.5)	0.07
FEV1/FVC, %	84±8.19	83.27±7.05	54.96±9.79^b-c	48.29±14.54^b-d	<0.001^a
FEV1% predicted	103.98±21.46	100.73±16.89	55.26±15.56^b-c	52.69±25.08^b-c	<0.001^a
MEF50	87.35±36.93	88.26±24.7	16.73±9.7^b-c	18.76±14.06^b-c	<0.001^a
MEF25	90.73±47.1	99.08±46.16	12.93±8.25^b-c	18.44±12.64^b-c	<0.001^a
MEF75/25	81.47±37.83	88.85±25.2	14.77±8.15^b-c	17.54±12.27^b-c	<0.001^a
WBC, 10^9/L	5.39±1.85	5.79±1.9	6.31±2.7	6.51±1.9^b	0.041^a
CRP, ug/ml	1.51±1.75	1.59±1.86	8.11±18.91^b	6.56±13.89^b	0.069

Notes: Data are presented as mean ± SD. ^aSignificant differences among all groups; ^bsignificantly different compared to healthy never-smoker; ^csignificantly different compared to healthy smoker; ^dsignificantly different compared to never-smoking patients.

Abbreviations: BMI, body mass index; CRP, C-reactive protein; FEV1, forced expiratory volume in one second; FVC, forced vital capacity;MEF, maximum expiratory flow; WBC, white blood cells.

Figure 1 Levels of SDCs in subjects. Both SDC-1 and SDC-4 showed a downward trend in COPD patients (A-B), but the differences in the levels of SDCs between never smoking and ever-smoking controls were not observed (C-D).

Abbreviations: COPD, chronic obstructive pulmonary disease; SDC, syndecan.

Table 2 Correlations of SDCs with lung function parameters in all subjects

	SDC-1		SDC-4
	rho	P-value	rho	P-value
FEV1/FVC ratio	0.36	<0.001	0.067	0.346
FEV1% predicted	0.248	0.002	0.034	0.674
MEF50	0.337	<0.001	0.072	0.371
MEF25	0.327	<0.001	0.088	0.272
MEF75/25	0.339	<0.001	0.024	0.768

Abbreviations: FEV1, forced expiratory volume in one second; FVC, forced vital capacity; MEF, maximum expiratory flow; SDC, syndecan.

Figure 2 Diagnostic accuracy of serum SDC-1 for COPD. Area under the curves (AUC) was calculated by the trapezoidal rule.

Figure 3 COPD patients with frequent exacerbations (FEs) had higher levels of CRP and lower levels of SDC-1 (A-B). Serum SDC-1 correlated negatively with CRP in COPD patients (C). Diagnostic accuracy of serum SDC-1 to differentiate FE was calculated (D).

Abbreviations: CRP, C-reactive protein; COPD, chronic obstructive pulmonary disease; SDC, syndecan.

Table 3 Multivariate linear analysis with circulating SDC-1 as dependent variable

	β	P-value
Age	0.015	0.856
Sex	−0.106	0.318
BMI	0.107	0.204
Smoking status	−0.044	0.668
WBC, 10^9/L	−0.09	0.285
CRP, ug/ml	−0.175	0.031

Abbreviations: BMI, body mass index; CRP, C-reactive protein; WBC, white blood cells.

Figure S1 Serum SDC-1 correlated positively with the ratio of FEV1/FVC (A) and the parameters of small airway obstruction (SAO) (B-D) in all subjects.

Abbreviations: FEV1, forced expiratory volume in one second; FVC, forced vital capacity; SDC, syndecan.