Difference of Serum Cytokine Profile in Allergic Asthma Patients According to Disease Severity

Figures & data

Table 1 Baseline Characteristics of Patients with Mild and Moderate-to-Severe Allergic Asthma

	Mild	Moderate-to-Severe	P value
N	22	18
Male: Female	9:13	7:11	0.897
Age, years	32.3±9.6	44.0±15.0	0.005**
BMI, kg/m^2	23.2±3.3	23.4±4.5	0.849
Smoking status, current: past: never	0:1:21	0:1:17	0.884
FVC, %predicted	98.77±10.36	78.03±18.44	<0.001***
FEV1, %predicted	95.36±12.53	63.64±25.06	<0.001***
FEV1/FVC, %predicted	96.91±11.52	79.20±22.75	0.007**
MEF75, %predicted	91.49±19.44	51.18±33.13	<0.001***
MEF50, %predicted	79.55±19.67	49.06±40.87	0.013*
MEF25, %predicted	70.55±28.06	46.05±43.35	0.078
ACT score	22.72±1.81	17.53±4.45	0.002**
IgE, kU/L	761.9±1164.7	473.2±834.7	0.501
Allergen, positive result (number, %)
Mold	2, 9.1%	7, 38.9%	0.025*
Dust mite	21, 95.4%	11, 61.1%	0.007**
Cat dander	7, 31.8%	2, 11.1%	0.119
Dog dander	7, 31.8%	4, 22.2%	0.499
Cockroach	5, 22.7%	1, 5.6%	0.130

Notes: Data are presented as mean ± standard deviation or number, percentage. *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: BMI, body mass index; FVC, forced vital capacity; FEV1, forced expiratory volume in the first second; MEF, maximal expiratory flow; ACT, asthma control test; IgE, immunoglobulin E.

Table 2 Serum Cytokine Levels in Mild and Moderate-to-Severe Allergic Asthma Patients

	Mild (pg/mL)	Moderate-to-Severe (pg/mL)	P value
Th1-related cytokines
IFN-γ	15.0327±18.5494	9.9081±5.4423	0.265
IP-10	219.5332±81.9197	179.8225±67.2624	0.107
TNF-β	1.3760±1.1251	1.6338±0.6957	0.402
IL-18	382.3738±180.2698	437.5303±237.5416	0.409
Th2-related cytokines
IL-4	0.0552±0.1760	0.0715±0.0508	0.168
IL-5	0.8976±0.4461	1.0189±0.6217	0.477
IL-6	1.9240±3.6287	10.6227±37.7049	0.343
IL-13	2.9740±1.4682	3.6162±0.9953	0.115
IL-17E	1.4924±0.8692	1.2052±0.7952	0.300
IL-31**	13.3371±6.2233	7.9754±3.7165	0.004**
IL-33	0.8603±0.5922	0.5982±0.2588	0.071
TARC	179.4743±325.5475	248.3678±154.6949	0.415
TSLP	1.4226±0.5462	1.3881±0.4468	0.831
Th9-related cytokine
IL-9	0.5086±0.5584	0.3077±0.2093	0.157
Th17-related cytokines
IL-17A	3.8704±2.6369	3.0720±1.6177	0.269
IL-21	67.1995±146.7237	3.1749±1.8464	0.053
IL-22	0.7479±0.9150	0.6558±0.3282	0.687
IL-23**	2.3996±1.7093	0.9643±0.9247	0.008**
Treg-related cytokine
IL-10	0.4019±0.1935	0.4314±0.1231	0.579
Monocyte-related cytokines
IL-27	650.1278±315.4457	759.9686±469.0485	0.383
IL-1β	3.9250±16.9320	4.6160±18.2887	0.902
MCP-1**	134.0964±59.9890	206.7393±83.5712	0.003**
MCP-2*	38.4753±13.8157	49.2572±13.6278	0.018*
MCP-3*	4.7400±1.7576	6.7599±3.9217	0.036*
MCP-4	99.7898±109.3274	133.5642±70.0432	0.264
Eosinophil-related cytokines
Eotaxin-1***	101.8066±149.2978	191.8802±83.5456	<0.001***
Eotaxin-2*	1203.4756±901.7847	1938.4275±936.9545	0.017*
Eotaxin-3	84.7753±133.9955	37.7562±20.2448	0.119
GM-CSF	0.0733±0.0430	0.0911±0.0837	0.391
Airway remodeling-related cytokines
VEGF-A	74.0250±74.6739	111.3350±61.3555	0.097
SDF-1α	842.2624±263.7370	893.5355±255.9779	0.539
YKL-40*	23,210.1859±15,116.1899	51,974.8527±54,283.5695	0.022*
TRAIL*	134.3080±37.1827	110.7160±34.0288	0.045*

Notes: Data are presented as mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: Th, T helper cell; IFN-γ, interferon-γ; IP-10, interferon-γ-induced protein 10; TNF-β, tumor necrosis factor-β; IL, interleukin; TARC, thymus and activation-regulated chemokine; TSLP, thymic stromal lymphopoietin; MCP, monocyte chemoattract protein; GM-CSF, granulocyte-macrophage colony-stimulating factor; VEGF-A, vascular endothelial growth factor-A; SDF-1α, stromal derived factor-1α; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.

Figure 1 Serum cytokine concentrations of the most discriminative biomarkers (A) IL-23 and IL-31, (B) eotaxin-1 and eotaxin-2, (C) MCP-1, MCP-2 and MCP-3, (D) YKL-40 and TRAIL in mild and moderate-to-severe allergic asthmatics. *P<0.05; **P<0.01; ***P<0.001.

Figure 2 Correlation matrix for 9 discriminative biomarkers with all 33 cytokines tested. Blue represented a negative correlation index while red represented a positive one. The darker the color, the higher the correlation index was.

Figure 3 Receiver operating characteristic (ROC) curves of YKL-40, eotaxin-1, MCP-1, IL-23, IL-31, eotaxin-2, MCP-2 and MCP-3 for discriminating mild and moderate-to-severe allergic asthmatics.

Table 3 The AUC, Cut-off, Sensitivity and Specificity Values for Mild and Moderate-to-Severe Allergic Asthma Patients

	AUC	P value	Cut-off (pg/mL)	Sensitivity (95% CI)	Specificity (95% CI)
YKL-40	0.833	<0.001***	33,753	72.22 (49.13–87.50)	90.91 (72.19–98.38)
Eotaxin-1	0.811	<0.001***	134.1	72.22 (49.13–87.50)	72.73 (51.85–86.85)
MCP-1	0.760	0.005**	142.9	77.78 (54.79–91.00)	72.73 (51.85–86.85)
IL-23	0.754	0.015*	1.035	71.43 (45.35–88.28)	83.33 (60.78–94.16)
IL-31	0.749	0.014*	11.78	86.67 (62.12–97.63)	57.89 (36.28–76.86)
Eotaxin-2	0.725	0.016*	1210	83.33 (60.78–94.16)	54.55 (34.66–73.08)
MCP-2	0.720	0.018*	43.06	66.67 (43.75–83.72)	72.73 (51.85–86.85)
MCP-3	0.707	0.026*	5.847	61.11 (38.62–79.69)	72.73 (51.85–86.85)

Notes: *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: AUC, area under curve; CI, confidence interval.

Table 4 Correlations Between Cytokine Levels and Lung Function Parameters

Parameter	Cytokine	Correlation Coefficient	P value
FEV1%	YKL-40	−0.478	0.003**
	Eotaxin-1	−0.472	0.003**
	Eotaxin-2	−0.418	0.010*
	TARC	−0.372	0.023*
	MCP-3	−0.372	0.023*
	IL-21	0.326	0.049*
FVC%	YKL-40	−0.506	0.001**
	Eotaxin-1	−0.477	0.003**
	IL-22	−0.428	0.008**
	MCP-3	−0.423	0.009**
	TARC	−0.385	0.019*
FEV1/FVC	Eotaxin-2	−0.434	0.007**
	Eotaxin-1	−0.411	0.012**
	IL-23	0.397	0.015*
	IL-31	0.350	0.034*
MEF75%	Eotaxin-1	−0.440	0.006**
	Eotaxin-2	−0.432	0.008**
	YKL-40	−0.394	0.016*
MEF50%	Eotaxin-2	−0.479	0.003**
	Eotaxin-1	−0.404	0.013*
	YKL-40	−0.376	0.022*
	IL-23	0.329	0.047*
MEF25%	Eotaxin-2	−0.443	0.006**
	Eotaxin-1	−0.390	0.017*
	YKL-40	−0.366	0.026*

Notes: Correlations between serum cytokine levels and FEV1%, FVC%, FEV1/FVC%, MEF75%, MEF50% and MEF25% were analyzed. All correlations listed above were evaluated using Spearman correlation coefficient analysis. *P<0.05; **P<0.01.

Abbreviations: FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; MEF, maximal expiratory flow.

Figure 4 Correlation matrix for lung function parameters with all 33 cytokines tested. Blue represented a negative correlation index while red represented a positive one. The darker the color, the higher the correlation index was.

Table 5 Correlations Between Serum Cytokine Levels and Exhaled Nitric Oxide Levels

Parameter	Cytokine	Correlation Coefficient	P value
FeNO	IP-10	0.417	0.042*
CaNO	IL-1β	0.487	0.018*
	IL-4	0.450	0.031*
FnNO	IL-25	0.566	0.009**
	IL-9	0.486	0.030*
	GM-CSF	0.469	0.037*
	Eotaxin-2	−0.463	0.040*
	IL-4	0.459	0.042*
	IL-31	0.449	0.047*

Notes: Correlations between serum cytokine levels and FeNO, CaNO and FnNO were analyzed. All correlations listed above were evaluated using Spearman correlation coefficient analysis. *P<0.05; **P<0.01.

Abbreviations: FeNO, fractional exhaled nitric oxide; CaNO, alveolar nitric oxide; FnNO, nasal nitric oxide.

Figure 5 Correlation matrix for FeNO, CaNO and FnNO levels with all 33 cytokines tested. Blue represented a negative correlation index while red represented a positive one. The darker the color, the higher the correlation index was.