Proteoglycan 4 is a diagnostic biomarker for COPD

Figures & data

Table 1 Baseline characteristics of the healthy control subjects, healthy smokers, and COPD patients with GOLD stages 1+2 and 3+4 for the biomarker selection study population

Categorical variables	Healthy controls (n=10)	Healthy smokers (n=5)	GOLD 1+2 (n=19)	GOLD 3+4 (n=42)
Age, years	67.8±6.2	59.8±14.6	72.4±7.5	70.0±8.9
Men, %	75	75	100	93
BMI, kg/m^2	22.5±2.9	24.8±4.0	24.6±2.9	23.5±3.8
Current smoking, %	0	100	21	17
1-year frequency of AEs (number of patients)	0	0	0.4 (6)	0.6 (15)
FEV1, % predicted	88.0±11.5	85.5±14.9	61.4±7.8	35.0±12.2
1-year change of FEV1, % predicted	ND	ND	−4.5±25.1	−4.5±9.6
FVC, % predicted	86.8±15.6	80.6±7.9	79.4±15.5	59.8±15.6
1-year change of FVC, % predicted	ND	ND	−2.1±20.7	−3.9±20.2
FEV1/FVC, % predicted	79.8±4.8	77.9±1.8	56.4±8.2	44.7±8.7
1-year change of FEV1/FVC, % predicted	ND	ND	−6.3±8.2	−2.8±7.4

Note: Data are presented as mean ± standard deviation.

Abbreviations: AE, acute exacerbation; BMI, body mass index; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; GOLD, Global initiative for chronic Obstructive Lung Disease; ND, no data.

Figure 1 Venn diagrams showing (A) common among or unique to patients with COPD GOLD stages 1, 2, 3, and 4 compared with the healthy controls and (B) common among patients with COPD GOLD stages 1, 2, 3, and 4.

Abbreviation: GOLD, Global initiative for chronic Obstructive Lung Disease.

Figure 2 CRP and PRG4 in COPD and COPD with AE.

Notes: (A) Serum CRP levels in healthy controls, healthy smokers, and subjects with COPD GOLD stages 1+2 and 3+4. (B) Serum CRP levels in healthy controls, healthy smokers, and COPD patients with AEs =0 and AEs ≥1. (C) Serum PRG4 levels in healthy controls, healthy smokers, and subjects with COPD GOLD stages 1+2 and 3+4. (D) Serum PRG4 levels in healthy controls, healthy smokers, and COPD patients with AEs =0 and AEs ≥1. ^&P<0.05 compared with healthy controls; ^$P<0.05 compared with healthy smokers; *P<0.05 between groups.
Abbreviations: AE, acute exacerbation; GOLD, Global initiative for chronic Obstructive Lung Disease; CRP, C-reactive protein; PRG4, Proteoglycan 4.

Figure 3 Performance of serum (A) CRP and (B) PRG4 in the ROC curve analyses in COPD.

Abbreviations: ROC, receiver operating characteristic; CRP, C-reactive protein; PRG4, Proteoglycan 4.

Table 2 Baseline characteristics of the healthy control subjects and COPD patients with GOLD stages 1+2 and 3+4 for the PRG4 validation study population

Categorical variables	Healthy controls (n=33)	GOLD 1+2 (n=30)	GOLD 3+4 (n=16)
Age, years	59.7±8.6	65.4±7.6	65.4±10.5
Men, %	24	93	81
BMI, kg/m^2	23.7±2.9	22.9±3.7	22.5±3.9
Current smoking, %	0	30	31
FEV1, % predicted	87.9±12.4	68.0±10.0	38.2±10.0
FVC, % predicted	86.5±10.3	78.4±16.9	58.3±16.6
FEV1/FVC, % predicted	78.9±5.1	68.0±9.3	53.6±9.0

Note: Data are presented as mean ± standard deviation.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; GOLD, Global initiative for chronic Obstructive Lung Disease; PRG4, Proteoglycan 4.

Table 3 PRG4 prediction of COPD in 79 subjects

	PRG4 (ng/mL)
	≤7.892	>7.892
Healthy nonsmokers	0.79 (TN)	0.09 (FP)
COPD patients	0.17 (FN)	0.93 (TP)

Note: The cutoff value of 7.892 ng/mL for PRG4 was used to validate the accuracy of COPD prediction.

Abbreviations: FN, false negative; FP, false positive; TN, true negative; TP, true positive; PRG4, Proteoglycan 4.

Figure 4 Correlation between CRP and PRG4 in COPD subjects.

Abbreviations: CRP, C-reactive protein; PRG4, Proteoglycan 4.

Figure 5 The relationship of serum (A) CRP and (B) PRG4 levels to 1-year changes in predictive (a) FEV₁%, (b) FVC%, and (c) FEV₁/FVC% in COPD.

Notes: The study subjects were divided equally based on quintiles of CRP and PRG4. The values in parentheses on the x-axes represent the mean PRG4 values for each quintile group. Linear regression was used to examine the correlation of quintiles of CRP and PRG4 with 1-year changes in FEV₁%, FVC%, and FEV₁/FVC%.
Abbreviations: FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; CRP, C-reactive protein; PRG4, Proteoglycan 4.