Analysis of Systemic Biomarkers in COPD Patients

Figures & data

Table 1.  Clinical Characteristics of COPD Patients and Control Individuals with and Without AAT‐Deficiency

Subject group characteristics	Control subjects	Asymptomatic subjects	COPD patients
	PiMM AAT (n = 20)	PiZZ AAT (n = 10)	PiZZ AAT (n = 10)	PiMM AAT (n = 10)
Male/Female	11/9	5/5	5/5	5/5
Age (years)	53 ± 9.6	47.4 ± 11	57 ± 12	59.4 ± 6.7
Smoking history
Never smokers	9	6	3	0
Exsmokersa	10	3	6	8
Smokersb	1	1	1	2
FEV1% of predictedc	95.9 ± 17	94 ± 12	43 ± 13	37 ± 16
FVC% of predicted	92.8 ± 17	94 ± 14	63 ± 12	50 ± 15
FEV1/FVC% ratio	76 ± 8	77 ± 10	50 ± 15	40 ± 20
Medication
No medication	20	6	–	–
Inhaled corticosteroids	–	3	7	10
Bronchodilatators	–	–	10	8
Diuretics	–	–	3	3
Continuous oxygen	–	–	1	1
Anti‐inflammatory	–	–	–	–
Anti‐depressants	–	1	–	1

^aExsmokers, stopped smoking at least 3 months before the study.

^bCurrent smokers.

^cMeasured after bronchodilatation.

Values are expressed as mean ± SD.

Table 2.  Correlations Between Measured Parameters

	MMP‐9	MCP‐1	IL‐8	VEGF	sICAM‐1	AAT‐polymers	sE‐selectin
MCP‐1	0.40**	x
IL‐8	0.37**	0.56***	x
VEGF	0.41**	0.30*	0.56***	x
sICAM‐1	0.19	0.06	0.38**	0.29	x
AAT‐polymers	0.12	− 0.11	− 0.04	0.00	0.53***	x
sE‐selectin	0.18	− 0.22	− 0.03	0.15	0.31*	0.57***	x
AAT	0.18	0.16	0.13	0.23	− 0.28	− 0.75***	− 0.31*

*, **, *** denote significant correlation at the 0.05, the 0.01 and the 0.001 level (2‐tailed), respectively.

Figure 1. Factor loading plot. The plot displays the rotated two‐factor solution where each variable is plotted according to its factor loadings. The high factor loadings (> 0.6, bold) of IL‐8, VEGF, MCP‐1 and MMP‐9 indicate strong association with the first factor, while AAT‐polymers and sE‐selectin are strongly positively and AAT is strongly negatively associated with the second factor. sICAM‐1 (underlined), on the other hand, is intermediately associated with both factors. Extraction method: Principal Component Analysis. Rotation method: Varimax with Kaiser Normalization. *—presents natural logarithm of serum concentration.

Table 3.  Measured Biomarkers in Serum From Control and COPD Individuals with and Without PiZZ AAT‐Deficiency

Biomarkers	Control				COPD
	PiMM AAT (n = 10)		PiZZ AAT (n = 10)		PiMM AAT (n = 10)		PiZZ AAT (n = 20)
	Meana	95% CI	Meana	95% CI	Meana	95% CI	Meana	95% CI
MMP‐9 (ng/ml)	329.5	252–431	353.5	230.5–542.2	841.3	504.1–1404	527.5	340.6–817
MCP‐1 (pg/ml)	197.5	129.9–300	195.6	88–434.6	216.5	98.2–477.3	145.7	76.4–277.7
VEGF (pg/ml)	140.6	115–171	99.3	76.9–128.3	183.4	124.5–270.4	143.8	93.4–221.6
sICAM‐1 (ng/ml)	97.4	79.5–119.4	153.9	124.8–189.7	151.2	114.2–200.1	166.6	138.3–202.7
AAT‐polymers (µg/ml)	4.5	3.2–6.2	42.1	22.6–78.2	9.7	5.9–15.8	94.8	64.4–139.7
AAT (mg/ml)	1.374b	1.28–1.46	0.202b	0.179–0.225	1.728b	1.573–1.883	0.319b	0.182–0.456
IL‐8 (pg/ml)	8.4	6.6–10.6	5.3	3–9.4	8.3	4.4–15.8	6.21	4.3–9
sE‐selectin (pg/ml)	16.6	8–34.2	55.5	41.3–74.7	55.3	42.7–71.2	66	48.9–89.2

^aVariables presented as a geometric mean.

^bVariable presented as a mean.