A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Characteristics of Study Population

Variable	Healthy (n=35)	S-COPD (n=35)	AE-COPD (n=35)	P value
Gender (female/male)	7/28	5/30	6/29	0.818
Age (years)	65.49±6.14	67.20±9.18	68.06±7.60	0.371
BMI (kg/m^2)	25.57±3.31	24.12±3.20	23.70±3.85	0.065
Smoking history (no/yes)	14/21	12/23	11/24	0.747
FEV1/FVC	82.68±6.02	49.20±13.44	39.46±10.62	<0.001
FEV1%pre	98.56±16.73	53.18±17.78	38.53±11.70	<0.001
GOLD Stage
1		4
2		16
3		13
4		2
mMRC		1.63±1.17
CAT		18.91±7.51
FeNO (ppb)	18.26±7.24	23.37±10.68		0.039^#
CaNO (ppb)	2.52±0.90	6.55±3.19		<0.001^#

Notes: Data were presented as mean ± SEM. ^#Healthy VS S-COPD.

Abbreviations: S-COPD, stable COPD; AECOPD, acute exacerbating COPD; BMI, body mass index; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; mMRC, modified British Medical Research Council; CAT, COPD assessment test; FeNO, fraction of exhaled nitric oxide; CaNO, concentration of alveolar nitric oxide.

Figure 1 (A and B) Expression levels of A2M and MMP-9 in plasma between stable COPD patients and healthy group by ELISA were measurement. (C) Pearson’s correlation analysis was employed to reveal the relationship between A2M and MMP9. (D) MMP-9/A2M ratio in stable COPD patients compared with the control groups. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. ****P < 0.0001.

Table 2 Correlation Between A2M, MMP-9, MMP-9/A2M and Clinical and Lung Function Indexes of Stable COPD Patients

		CAT Score	mMRC Score	FeNO	CaNO	FEV1%pre	FEV1/FVC
A2M	r	−0.847	−0.809	−0.002	0.084	0.805	0.505
	P	0.000	0.000	0.989	0.749	0.000	0.002
MMP-9	r	0.521	0.562	0.183	0.011	−0.487	−0.345
	P	0.001	0.000	0.316	0.966	0.003	0.043
MMP-9/A2M	r	0.604	0.634	0.120	−0.025	−0.561	−0.390
	P	0.000	0.000	0.514	0.924	0.000	0.021

Abbreviations: A2M, α 2 macroglobulin; MMP-9, Matrix metalloproteinase-9; mMRC, modified British Medical Research Council; CAT, COPD assessment test; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; FeNO, fraction of exhaled nitric oxide; CaNO, concentration of alveolar nitric oxide.

Figure 2 (A and B) Expression levels of A2M and MMP-9 between healthy nonsmoking group, healthy smoking group, COPD nonsmoking group and COPD smoking group. Differences between the groups were assessed by one-way analysis of variance. NS: no significant (P > 0.05), *P < 0.05.

Figure 3 (A and B) Performances of A2M and MMP-9/A2M in the diagnosis of COPD.

Figure 4 (A) Expression levels of MMP-9 between stable COPD group and AECOPD group. (B) Value of MMP-9 in predicting acute exacerbation of COPD. (C) Based on two-sample independent Student’s t-test analysis, expression levels of A2M between stable COPD group and AECOPD group. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. NS: no significant (P > 0.05), ****P < 0.0001.

Figure 5 Expression levels of A2M between non-infection AECOPD group and infection AECOPD group. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. ****P < 0.0001.

Table 3 Characteristics of AECOPD Patients (with or Without Infection)

Variable	NI-AECOPD (n=35)	I-AECOPD (n=35)	Statistic	P value
Gender (female/male)	7/28	6/29	χ^2=0.094	0.759
Age (years)	73.97±9.07	71.14±10.17	t=1.228	0.224
BMI (kg/m^2)	23.33±4.16	22.45±3.88	t=0.916	0.363
Smoking history (no/yes)	11/24	11/24	χ^2=0.000	1.000
FEV1/FVC	43.48±11.47	49.71±20.21	t=−1.324	0.194
FEV1%pre	41.30±16.34	46.32±19.52	t=−0.990	0.327

Note: Data were presented as mean ± SEM.

Abbreviations: NI-AECOPD, Non-infection acute exacerbating COPD; I-AECOPD, infection acute exacerbating COPD; BMI, body mass index; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.