Increased serum TRAIL and DR5 levels correlated with lung function and inflammation in stable COPD patients

Figures & data

Table 1 Characteristics of patients with COPD and healthy subjects

Characteristic	COPD patients	Healthy controls	P-value
Sex (male/female)	39/18	21/14	0.500
Age (years)	61.95±11.30	57.51±11.79	0.076
Smoker/nonsmoker	26/31	12/23	0.383a
Pack-years (in smoker)	23.23±12.79	25.83±13.95	0.572
FEV1 (L)	1.97±0.58	2.69±0.80	0.000
FVC (L)	3.27±0.83	3.41±1.03	0.458
FEV1% predicted	81.63±20.85	110.73±18.20	0.000
FEV1/FVC	60.08±9.82	80.47±5.74	0.000
BMI (kg/m^2)	23.44±3.44	24.26±3.50	0.310
SO2 (%)	96.56±1.72	96.57±1.61	0.97
TRAIL (pg/mL)	50.17±17.70	42.09±15.49	0.029
DR5 (pg/mL)b	48.15±22.88	38.94±10.95	0.032
TNF-α (pg/mL)b	15.47±14.71	14.82±21.46	0.041
CRP (µg/mL)b	2.33±2.89	1.20±1.29	0.026

Notes: Data are presented as mean ± SD.

a The χ² test was used to test the significance of the difference in sex proportions.

b As distributions of these parameters were skewed, log transformed values were used in the statistical analyses.

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DR5, decoy receptor 5; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SD, standard deviation; SO₂, oxygen saturation; TNF-α, tumor necrosis factor-α; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Table 2 Characteristics of multigroups

Characteristic	Healthy nonsmokers	Healthy smokers	Nonsmokers with COPD	Smokers with COPD	P-value
Sex (male/female)	9/14	12/0	13/18	26/0	0.000a
Age (years)	56.74±11.13	59.00±13.98	61.61±12.13	62.35±10.46	0.324
Pack-years (in smoker)	0	22.52±11.57	0	24.78±14.08	0.000a
FEV1 (L)	2.43±0.72	3.23±0.59	1.88±0.58	2.09±0.55	0.000
FVC (L)	3.06±0.90	4.13±0.71	3.04±0.77	3.61±0.78	0.000
FEV1% predicted	110.83±18.72	107.66±12.64	85.03±22.07	77.65±16.87	0.000
FEV1/FVC	81.71±5.22	78.32±6.00	61.59±9.89	57.92±9.74	0.000
BMI (kg/m^2)	24.45±3.59	23.75±3.70	23.66±3.70	23.18±3.14	0.662
SO2 (%)	96.57±1.56	96.58±1.78	96.36±1.77	96.79±1.68	0.836
TRAIL (pg/mL)	42.65±12.22	41.03±21.00	45.55±17.65	55.68±16.44	0.019
DR5 (pg/mL)b	38.71±11.34	39.38±10.64	42.35±19.22	55.06±25.26	0.009

Notes: Data are presented as mean ± SD.

a There is no difference between healthy smokers and smokers with COPD.

b The data were log transformed in the statistical analyses.

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; DR5, decoy receptor 5; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SD, standard deviation; SO₂, oxygen saturation; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Figure 1 Levels of TraIl (A) and DR5 (B) in plasma from the non-COPD group and COPD group.

Notes: Circulating TRAIL and DR5 concentrations were measured using multiplex enzyme-linked immunosorbent assay. COPD patients had significantly elevated TRAIL and DR5 levels when compared with those in healthy controls (P=0.029 and P=0.032, respectively). DR5 was log transformed in the statistical analyses. The expression of TRAIL and DR5 are presented as mean (error bar) and compared by unpaired Student’s t-test (*P<0.05).

Abbreviations: COPD, chronic obstructive pulmonary disease; DR5, decoy receptor 5; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Figure 2 Multigroup analysis: TRAIL and DR5 in the plasma from the healthy nonsmokers group, healthy smokers group, COPD nonsmokers group, and COPD smokers group.

Notes: (A) TRAIL was highly expressed in the smoking COPD compared with nonsmokers with COPD, healthy smokers, and healthy nonsmokers (P=0.024, P=0.013, and P=0.007, respectively); (B) a similar tendency was in DR5 (P=0.008, P=0.021, and P=0.002, respectively). There was no difference between the healthy nonsmokers and smokers. DR5 was log transformed in the statistical analyses. The levels of TRAIL and DR5 are presented as mean (error bar) and compared by one-way analysis of variance (*P<0.05).
Abbreviations: COPD, chronic obstructive pulmonary disease; DR5, decoy receptor 5; NS, nonsmokers; S, smokers; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Table 3 Correlations between TRAIL, lung function, and TNF-α

	TRAIL (pg/mL) (COPD)	TRAIL (pg/mL) (total subjects)
FEV1% predicted	r=−0.354, P=0.007	r=−0.291, P=0.005
FEV1/FVC	r=−0.32, P=0.013	r=−0.321, P=0.002
TNF-α (pg/mL)	r=0.371, P=0.005	r=0.349, P=0.001

Notes: TNF-α was log transformed in the statistical analyses. Correlations between variables were analyzed by Pearson’s correlation coefficient.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; TNF-α, tumor necrosis factor-α; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Table 4 Correlations between DR5, lung function, and CRP

	DR5 (pg/mL) (COPD)	DR5 (pg/mL) (total subjects)
FEV1% predicted	r=−0.394, P=0.002	r=−0.315, P=0.002
FEV1/FVC	r=−0.316, P=0.017	r=−0.358, P=0.000
CRP (ng/mL)	r=0.158, P=0.24	r=0.240, P=0.021

Notes: DR5 and CRP were log transformed in the statistical analyses. Correlations between variables were analyzed by Pearson’s correlation coefficient.

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DR5, decoy receptor 5; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; TNF-α, tumor necrosis factor-α.

Figure 3 TraIl and DR5 were correlated with pulmonary function.

Notes: TraIl in the serum was inversely correlated with (A) FEV₁% predicted (r=−0.354, P=0.007 for COPD; r=−0.291, P=0.005 for all participants) and (B) FEV₁/FVC (r=−0.32, P=0.013 for COPD; r=−0.321, P=0.002 for all participants). DR5 was inversely correlated with (C) FEV₁% predicted (r=−0.394, P=0.002 for COPD; r=−0.315, P=0.002 for total subjects) and (D) FEV₁/FVC (r=−0.316, P=0.017 for COPD; r=−0.358, P=0.000 for total subjects). DR5 was log transformed in the statistical analyses. The orange solid line denotes the line of best fit in COPD, the blue line represents the line of best fit in all subjects, and Pearson’s correlation coefficient is presented as an r-value.

Abbreviations: COPD, chronic obstructive pulmonary disease; DR5, decoy receptor 5; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Figure 4 Correlation analyses between TRAIL/DR5 levels and established COPD biomarkers.

Notes: (A) TraIl concentration was positively correlated with TNF-α in COPD (r=0.371, P=0.005) and in all participants (r=0.349, P=0.001). (B) DR5 levels was positively correlated with CRP in total subjects (r=0.24, P=0.021). DR5, CRP, and TNF-α were log transformed in the statistical analyses. The orange solid line denotes the line of best fit in COPD, the blue line represents the line of best fit in all subjects, and Pearson’s correlation coefficient is presented as an r-value.
Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DR5, decoy receptor 5; TNF-α, tumor necrosis factor-α; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.