PARC/CCL18 is Associated with Inflammation, Emphysema Severity and Application of Inhaled Corticosteroids in Hospitalized COPD Patients

Figures & data

Figure 1 The flowchart of this study.

Table 1 Clinical Characteristics of the Subjects

	COPD (n=98)	Healthy Control (n=60)	p value
Age (yrs)	71.48±8.60	63.31±7.78	–
Male, n (%)/Female	78 (79.59%)	32 (53.33%)	–
Disease duration (yrs)	10.10±8.66	–	–
Pack-years	26.78±18.58	19.54±24.17	–
Current smoker (%)	17 (17.35%)	14 (23.33%)	–
LOS (days)	7.36±3.24	–	–
CAT (score)	25.07±6.40	–	–
mMRC (score)	2.69±0.97	–	–
BMI (kg/m^2)	23.00±3.98	22.78±3.75	–
COPD severity, GOLD		–	–
Mild, I	18 (18.37%)
Moderate, II	21 (21.43%)
Serve, III	40 (40.82%)
Very serve, IV	19 (19.39%)
PARC, ng/mL	162.56±14.44	85.09±5.97	0.003

Notes: Analyzed by Mann–Whitney test. Data are presented as mean ± SD, or number. – means data lacking or not applicable. Bold text means p<0.05.

Abbreviations: COPD, chronic obstructive pulmonary disease; yrs, years; LOS, length of hospital stay; CAT, COPD Assessment Test; mMRC, modified British Medical Research Council; BMI, body mass index; PARC, pulmonary and activation-regulated chemokine.

Figure 2 Comparison of serum PARC/CCL18 concentration in COPD patients and healthy control. The central horizontal line on each box represents the average, the error bars 5% and 95%. P-values derived from the t-test. **Means p<0.01.

Abbreviations: PARC, pulmonary and activation-regulated chemokine; CCL-18, chemokine (C-C motif) ligand 18; COPD, chronic obstructive pulmonary disease.

Figure 3 Comparison of serum PARC/CCL18 concentration in different Grade (A) and with different mMRC scores (B) of COPD patients. Relationship between CAT (C), disease duration (D), LOS (E), BMI (F) and serum PARC concentration, respectively. The central horizontal line on each box represents the average, the error bars 5% and 95%, p-values derived from the t-test in (A) and (B). **Means p<0.01. The line in (C) to (F) represents the regression line of correlation analysis, Pearson correlation coefficients of r-values and p-values were shown at the top right of the picture.

Abbreviations: COPD, chronic obstructive pulmonary disease; yrs, years; LOS, length of hospital stay; CAT, COPD Assessment Test; mMRC, modified British Medical Research Council; BMI, body mass index; PARC, pulmonary and activation-regulated chemokine.

Figure 4 Correlation between WBC (A), Hb (B), Plt (C), Neut (D), Neut% (E), CRP (F) and serum PARC/CCL18 level, respectively. The line represents the regression line of correlation analysis, Pearson correlation coefficients of r-values and p-values were shown at the top right of the picture.

Abbreviations: PARC, pulmonary and activation-regulated chemokine; WBC, white blood cells; Hb, hemoglobin; Plt, blood platelet; Neut, neutrophil granulocyte; Eos, eosinophilic granulocyte; CRP, C-reactive protein.

Table 2 Clinical Characteristics of COPD Patients with Emphysema and Not

	Emphysema (n=61)	Non-Emphysema (n=37)	p value
Age (yrs)	70.48±1.02	73.15±1.46	0.127
Male, n (%)/Female	57 (93.44%)	21 (56.76%)	<0.0001
Disease duration (yrs)	9.94±1.02	10.36±1.62	0.814
Pack-years	29.07±3.33	14.26±2.85	0.008
Current smoker (%)	8 (13.11%)	9 (24.32%)	0.155
LOS (days)	7.734±0.45	6.74±0.41	0.136
CAT (score)	26.41±0.81	22.79±0.88	0.005
mMRC (score)	2.85±0.122	2.41±0.16	0.025
BMI (kg/m^2)	22.54±0.48	23.79±0. 70	0.131
COPD severity, GOLD
Mild, I	6 (9.84%)	9 (24.32%)	0.053
Moderate, II	12 (19.67%)	3 (8.11%)	0.123
Serve, III	30 (49.18%)	19 (51.35%)	0.835
Very serve, IV	13 (21.31%)	6 (16.22%)	0.536
WBC (/mL)	8.51±0.52	8.85±0.66	0.685
Hb (g/L)	132.1±2.04	127.9±3.19	0.248
Plt (/mL)	224.9±9.88	217.9±12.97	0.668
Neut (/mL)	6.39±0.51	6.09±0.57	0.706
Eos (/mL)	0.16±0.02	0.20±0.03	0.221
CRP (mg/L)	33.27±6.03	34.35±7.47	0.912
FEV1 (L)	1.24±0.14	1.35±0.21	0.669
FVC	2.15±0.17	1.95±0.21	0.470
RV (L)	2.72±0.21	1.910.15	0.019
TLC (L)	5.01±0.22	4.06±0.25	0.012
RV/TLC	0.55±0.02	0.48±0.02	0.044
PARC, ng/mL	184.4±19.86	117.0±15.99	0.049

Notes: Analyzed by Student’s t-test, Mann–Whitney test or chi-square test. Data are presented as mean ± SD, number (with percentage in parentheses). Bold text means p<0.05.

Abbreviations: COPD, chronic obstructive pulmonary disease; yrs, years; LOS, length of hospital stay; CAT, COPD Assessment Test; mMRC, modified British Medical Research Council; BMI, body mass index; WBC, white blood cells; Hb, hemoglobin; Plt, blood platelet; Neut, neutrophil granulocyte; Eos, eosinophilic granulocyte; CRP, C-reactive protein; RV, residual volume; TLC, total lung capacity; PARC, pulmonary and activation-regulated chemokine.

Figure 5 Correlation between RV (A), TLC (B), RV/TLC (C) and serum PARC level, respectively. (D) shows the comparison of serum PARC/CCL18 concentration in emphysema and non-emphysema patients. The line represents the regression line of correlation analysis, Pearson correlation coefficients of r-values and p-values were shown at the top right of the picture. The central horizontal line on each box represents the average, the error bars 5% and 95%. P-values derived from the t-test. *Means p<0.05.

Abbreviations: PARC, pulmonary and activation-regulated chemokine; RV, residual volume; TLC, total lung capacity.

Table 3 Clinical Characteristics of COPD Patients with ICS and Not

	ICS (n=59)	Non-ICS (n=39)	p value
Age (yrs)	73.32±1.13	68.36±1.12	0.001
Male, n (%)/Female	52 (88.14%)	31 (79.49%)	0.244
Disease duration (yrs)	11.18±1.25	8.62±1.15	0.148
Pack-years	17.34±20.16	29.21±28.49	0.067
Current smoker (%)	11 (18.64%)	6 (15.38%)	0.677
LOS (days)	8.000±0.47	6.49±0.37	0.020
CAT (score)	25.84±0.94	24.00±0.71	0.148
mMRC (score)	2.80±0.13	2.52±0.14	0.146
BMI (kg/m^2)	22.30±0.50	23.99±0.62	0.036
COPD severity, GOLD
Mild, I	13 (22.03%)	6 (15.38%)	0.415
Moderate, II	16 (27.11%)	9 (23.08%)	0.65
Serve, III	18 (30.51%)	17 (43.59%)	0.186
Very serve, IV	12 (20.34%)	7 (17.95%)	0.770
WBC (/mL)	8.05±0.53	8.83±0.63	0.691
Hb (g/L)	131.0±2.25	130.0±2.80	0.780
Plt (/mL)	211.2±9.36	237.8±13.20	0.094
Neut (/mL)	6.33±0.50	6.21±0.61	0.885
Eos (/mL)	0.18±0.02	0.17±0.03	0.735
CRP (mg/L)	39.95±7.22	24.96±4.7	0.114
FEV1	1.33±0.12	1.30±0.14	0.849
FVC	2.10±0.14	2.02±0.16	0.696
RV (L)	2.55±0.28	2.27±0.13	0.441
TLC (L)	4.63±0.31	4.46±0.21	0.680
RV/TLC	0.54±0.02	0.51±0.02	0.392
PARC, ng/mL	209.7±21.21	91.30±8.7	0.003

Notes: Analyzed by Student’s t-test, Mann–Whitney test or chi-square test. Data are presented as mean ± SD, number (with percentage in parentheses). Bold text means p<0.05.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroids; yrs, years; LOS, length of hospital stay; CAT, COPD Assessment Test; mMRC, modified British Medical Research Council; BMI, body mass index; WBC, white blood cells; Hb, hemoglobin; Plt, blood platelet; Neut, neutrophil granulocyte; Eos, eosinophilic granulocyte; CRP, C-reactive protein; RV, residual volume; TLC, total lung capacity; PARC, pulmonary and activation-regulated chemokine.

Table 4 Multivariate Logistic Regression of Factors Associated with ICS Application

Variables	OR (95% CI)	p value
Age (yrs)	0.991 (0.981–1.002)	0.051
LOS (days)	1.048 (0.843–1.304)	0.671
BMI (kg/m^2)	0.898 (0.761–1.058)	0.199
PARC, ng/mL	1.092 (1.009–1.192)	0.049

Note: Bold text means p<0.05.

Abbreviations: OR, odds ratio; CI, confidence interval; LOS, length of hospital stay; BMI, body mass index; PARC, pulmonary and activation-regulated chemokine.

Figure 6 ROC curve analysis of PARC/CCL18 for ICS application.

Abbreviation: AUC, area under the curve.