Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema

Figures & data

Figure 1. A flow diagram of study design. CC16: club cell protein 16; TGF-β1: transforming growth factor β1; ELISA: enzyme-linked immunosorbent assay; CPFE: combined pulmonary fibrosis and emphysema.

Table 1.  Basic characteristics of the three groups

	Smoker control (n = 36)	Emphysema alone (n = 115)	CPFE (n = 27)	All (n = 178)	p value
Age, years	64.5 ± 10.3	67.4 ± 8.9	74.9 ± 7.7	68.0 ± 9.5	<0.0001
Gender, M/F	30/6	109/6	24/3	163/15	NS
Pack-years	42.5 ± 27.8	78.7 ± 47.2	91.1 ± 56.8	73.5 ± 47.9	0.0005
COPD/non-COPD	15/21	104/11	14/13	133/45	<0.0001
GOLD I/II/III/IV	6/6/3/0	10/42/41/11	6/4/4/0	22/52/48/11	0.0042
Average upper LAA	16.6 ± 11.8	38.5 ± 15.7	30.9 ± 18.1	32.9 ± 17.6	<0.0001

The data were analyzed using ANOVA and are presented in the table as mean ± SD (range). M: male, F: female, COPD: chronic obstructive pulmonary disease, GOLD: global initiative for chronic obstructive lung disease, LAA: low attenuation area and NS: not significant.

Table 2.  Clinical manifestations

	Smoker control (n = 36)	Emphysema alone (n = 115)	CPFE (n = 27)	All (n = 175)	p value
FVC %	3.58 ± 0.93	3.29 ± 0.82	3.07 ± 0.75	3.32 ± 0.84	NS
FEV1/FVC %	73.7 ± 9.3	51.7 ± 13.7	68.7 ± 18.4	58.7 ± 16.8	<0.0001
FEV1 % predicted	93.6 ± 20.2	60.3 ± 22.3	82.4 ± 24.1	70.4 ± 26.1	<0.0001
DLCO %	112.6 ± 23.5	75.7 ± 22.8	62.4 ± 21.9	81.2 ± 28.1	<0.0001
PaO2 at rest	89.2 ± 8.5	81.5 ± 9.5	85.1 ± 10.3	83.7 ± 9.9	0.0002
PaCO2 at rest	40.9 ± 3.3	39.8 ± 4.1	41.4 ± 3.0	40.2 ± 3.8	NS
AaDO2	9.7 ± 8.4	18.8 ± 10.9	13.2 ± 10.7	16.0 ± 11.0	<0.0001
Distance, 6MWT	527.4 ± 68.8	469.3 ± 86.2	426.1 ± 87.8	474.5 ± 88.3	<0.0001
∆SpO2	0.9 ± 1.2	4.8 ± 5.0	5.5 ± 5.3	4.1 ± 4.8	<0.0001
Borg Scale	1.8 ± 1.5	3.1 ± 2.0	3.1 ± 2.1	2.9 ± 2.0	0.0019
LVEF	69.7 ± 5.0	68.5 ± 6.1	68.5 ± 5.7	68.8 ± 5.8	NS
Systolic PAP#	30.7 ± 5.2	34.9 ± 6.9	35.0 ± 8.3	34.1 ± 7.0	0.0127

The data were analyzed using ANOVA and are presented in the table as mean ± SD (range). FVC: forced vital capacity, FEV1: forced expiratory volume in one second, DLCO: diffusing capacity of the lung, PaO2: partial pressure of oxygen in arterial blood, PaCO2: partial pressure of carbon dioxide in arterial blood, AaDO2: Alveolar-arterial oxygen difference, 6MWT: 6-minute walking test, LVEF: left ventricular ejection fraction, PAP: pulmonary artery pressure, #: assessed by echocardiogram and NS: not significant.

Figure 2. Box-plot of the biomarkers among smoker control, emphysema alone and CPFE groups. (2A): serum concentrations of KL-6 among three groups (p < 0.0001). (2B): serum concentration of SP-D among three groups (p = 0.001). (2C): serum concentration of CC16 among three groups (p = 0.0009). KL-6: Krebs von den Lungen-6; SP-D: surfactant protein D; CC16: club cell secretory protein 16; CPFE: combined pulmonary fibrosis and emphysema. *p < 0.01, ^**p < 0.05, when compared between groups.

Figure 3. Receiver Operator Characteristic (ROC) analysis of the three combinations of biomarkers: The AUC for each combination was as follows: KL-6 and CC16 (Fig 3A), SP-D and CC16 (Fig 3B), KL-6, SP-D, and CC16 (Fig 3C) was 0.828, 0.804 and 0.813, respectively. Details of ROC analysis are provided in ETable 5. The combination of KL-6 and CC16 appeared better than the other two combinations. KL-6: Krebs von den Lungen 6, CC16: club cell secretory protein 16, SP-D: surfactant protein D, AUC: area under the curve.