Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

Figures & data

Table 1 Characteristics of healthy volunteers and COPD patients

Characteristics	Healthy controls (N=51)		COPD (N=84)		P-value
	Nonsmokers (HN, 33)	Smokers (HS, 18)	Nonsmokers (CN, 41)	Smokers (CS, 43)
Age, years	59.21±10.64	56.94±12.52	60.27±9.32	63.74±9.63	0.076
Sex, male/femalea	10/23	17/1	12/29	43/0	<0.001b
BMI, kg/m^2	23.04±5.40	20.11±7.75	23.50±2.79	22.50±2.75	0.057
Current smokers (%)	NA	14 (77.78)	NA	29 (67.44)	0.544a
Former smokers (%)	NA	4 (22.22)	NA	14 (32.56)
Pack-years for ever-smokers	NA	23.01±13.91	NA	28.15±20.48	0.356
Passive smoke exposure (%)a	11 (33.33)	5 (27.78)	10 (24.39)	10 (23.26)	0.771a
FEV1, L	2.28±0.84	3.11±0.56	1.68±0.50	2.05±0.71	<0.001b
FVC, L	2.99±0.95	4.04±0.62	2.87±0.62	3.72±0.81	<0.001b
FEV1/FVC, %	81.38±5.68	77.39±5.51	58.03±10.88	57.67±9.69	<0.001b
FEV1/Pre, %	110.00±19.05	111.44±15.05	79.37±21.31	81.70±19.24	<0.001b
FEV3/FVC, %	95.00±3.68	92.17±3.91	79.49±9.92	77.89±9.39	<0.001b
MMEF25–75, L/s	2.17±0.95	2.70±1.04	0.73±0.35	0.84±0.52	<0.001b
MMEF25–75/Pre, %	70.57±23.84	77.69±22.74	24.66±11.59	26.14±14.02	<0.001b
PAI-1, ng/mL	99.29±37.14	109.74±35.69	114.43±49.00	136.16±52.61c–e	0.006b
suPAR, pg/mL	697.26±366.34	698.12±339.84	797.06±412.79	746.52±507.10	0.829
CRP (μg/mL)	1.08±1.12	1.06±1.19	1.91±2.50	2.84±3.08c,d	0.005b

Notes: Data are presented as mean ± standard deviation;

a χ² test was used to test the significance of the difference between two groups;

b these characteristics are significantly different between groups;

c represents significance for CS versus HN;

d for CS versus HS;

e for CS versus CN. P<0.05 was considered to be statistically significant.

Abbreviations: COPD, chronic obstructive pulmonary disease; BMI, body mass index; kg/m², kilogram per square meter; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; MMEF, maximum midexpiratory flow; PAI-1, plasminogen activator inhibitor-1; suPAR, soluble urokinase-type activator receptor; CRP, C-reactive protein; NA, not applicable.

Figure 1 Serum PAI-1 levels in subjects.

Notes: Serum PAI-1 levels significantly increased in COPD smokers compared with other groups (A); meanwhile, it was higher in GOLD 2–4 COPD patients compared with healthy subjects and GOLD 1 COPD patients (B).
Abbreviations: PAI-1, plasminogen activator inhibitor-1; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Table 2 Correlations between serum PAI-1 levels, suPAR levels, and COPD-related characteristics in all subjects

Parameter	PAI-1 (justified)	suPAR (justified)
FEV1/FVC
r	−0.308	0.014
P	<0.001	0.873
FEV1/Pre
r	−0.295	−0.133
P	0.001	0.132
FEV3/FVC
r	−0.289	0.021
P	0.001	0.817
MMEF25–75/Pre
r	−0.273	−0.046
P	0.002	0.602
CRP
r	0.351	0.188
P	<0.001	0.032
TIMP-1
r	0.498	0.456
P	<0.001	<0.001
MMP-9
r	0.267	0.133
P	0.002	0.132
suPAR
r	0.210	–
P	0.016	–

Notes: The value of r represents the Pearson’s partial correlation coefficient adjusted for age, sex, BMI, cigarette status, and passive smoke exposure (in the column titled PAI-1 (justified)). P<0.05 was considered to be statistically significant. Data in bold indicates statistical significance.

Abbreviations: PAI-1, plasminogen activator inhibitor-1; suPAR, soluble urokinase-type activator receptor; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; FEV₁/FVC, ratio of FEV₁ to FVC; FEV₁/Pre, FEV₁ percent predicted; FEV₃/FVC, ratio of forced expiratory volume in 3 seconds to FVC; MMEF25–75, maximum midexpiratory flow; MMEF25–75/Pre, MMEF25–75 percent predicted; CRP, C-reactive protein; TIMP-1, tissue inhibitor of metalloproteinase-1; MMP-9, Matrix metalloproteinase-9; BMI, body mass index.

Figure 2 Circulating PAI-1 levels were related to lung function.

Notes: PAI-1 levels were reversely correlated with FEV₁/FVC (adjusted r=−0.308, P<0.001, (A) and FEV₁/predicted (adjusted r=−0.295, P=0.001, (B). The solid line denotes the line of best fit, and Pearson’s partial correlation coefficient is presented as an adjusted r-value.

Abbreviations: PAI-1, plasminogen activator inhibitor-1; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity.

Figure 3 Correlations between serum PAI-1 levels and established COPD-related biomarkers.

Notes: PAI-1 levels were positively correlated with CRP (adjusted r=0.351, P<0.001, A) and TIMP-1 (adjusted r=0.498, P<0.001, B). The solid line denotes the line of best fit, and Pearson’s partial correlation coefficient is presented as an adjusted r-value.
Abbreviations: PAI-1, plasminogen activator inhibitor-1; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein.

Table 3 Multivariable linear analysis for circulating PAI-1 levels

Parameter	β	P-value
Age	−0.2706	0.0003
Sex	−0.0471	0.5964
BMI	0.0315	0.6482
Smoking status	0.1095	0.2111
Passive smoke exposure	−0.0567	0.4086
FEV1/FVC	−0.2756	0.0004
CRP	0.1519	0.0487
TIMP-1	0.4191	<0.0001
MMP-9	0.0681	0.4280
suPAR	−0.0231	0.7652

Notes: The value of β represents standard regression coefficient. Bold denotes a value of P<0.05.

Abbreviations: BMI, body mass index; FEV₁/FVC, ratio of FEV₁ to FVC; CRP, C-reactive protein; TIMP-1, tissue inhibitor of metalloproteinase-1; MMP-9, Matrix metalloproteinase-9; suPAR, soluble urokinase-type activator receptor.