Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

Yoon Young Jang; Hyun Seok Lee; Ji Eun Jeong; Eun Joo Lee; Suk Jin Hong; Hye Jin Park; Kye Hyang Lee; Wootaek Kim; Hai Lee Chung

doi:10.4168/aard.2015.3.6.417

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Jang, Lee, Jeong, Lee, Hong, Park, Lee, Kim, and Chung: Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

Original Article

Allergy, Asthma & Respiratory Disease 2015; 3(6): 417-424.

Published online: 30 November 2015

DOI: https://doi.org/10.4168/aard.2015.3.6.417

Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

Yoon Young Jang, Hyun Seok Lee, Ji Eun Jeong, Eun Joo Lee, Suk Jin Hong, Hye Jin Park, Kye Hyang Lee, Wootaek Kim, Hai Lee Chung

Department of Pediatrics, Catholic University of Daegu School of Medicine, Daegu, Korea.

Correspondence to: Hai Lee Chung. Department of Pediatrics, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea Tel: +82-53-650-4245, Fax: +82-53-623-7507, hlchung@cu.ac.kr

Received 14 July 2015 Revised 14 September 2015 Accepted 19 September 2015

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Abstract

Purpose

Vascular endothelial growth factor (VEGF), transforming growth factor beta1 (TGF-β1), and platelet derived growth factor (PDGF) are known to be involved in the pathogenesis of inflammation and remodeling in asthmatic airways. YKL-40, a chitinase-like protein, and clusterin have been reported to be biomarkers for severe asthma. We examined the serum levels of growth factors, YKL-40, and clusterin in children with acute asthma or stable asthma, and investigated their correlation with clinical findings and lung function parameters.

Methods

Forty-one children (≥6 years of age) with asthma were enrolled, and 2 groups were defined: 23 patients admitted with acute asthma (acute asthma group) and 18 patients with stable asthma (stable asthma group). The serum levels of VEGF, TGF-β₁, PDGF-BB, YKL-40, and clusterin were measured using enzyme-linked immunosorbent assay and assessed in relation to clinical manifestations and spirometric parameters. Fifteen age-matched controls were also studied.

Results

The serum levels of VEGF, TGF-β₁, and YKL-40 were significantly elevated in children with acute asthma compared to controls. The serum levels of VEGF and YKL-40 were higher in the stable asthma group than in controls. The serum levels of VEGF, TGF-β₁, and YKL-40 were not different between the acute asthma and stable asthma groups. The serum VEGF levels in the acute asthma group correlated significantly with asthma severity. The serum TGF-β₁ levels in stable asthma group showed a significant inverse correlation with (FEV₁) forced expiratory volume in one second and FEF_25%-75% (forced expiratory flow between 25 and 75 percent of expired vital capacity). Serum YKL-40 had no significant relationship with clinical manifestations and spirometric parameters.

Conclusion

Our study suggests that increased serum levels of VEGF and YKL-40 might affect asthmatic airways not only during acute exacerbation but also in stable state and that serum TGF-β₁ might be a biomarker for airway obstruction in children with asthma.

Keywords: Asthma, Vascular endothelial growth factor, Transforming growth factor beta1, YKL-40

Figures and Tables

Fig. 1

Serum VEGF (A), TGF-β₁ (B), PDGF-BB (C), YKL-40 (D), and clusterin (E) levels in acute and stable asthma groups, and controls. VEGF, vascular endothelial growth factor; TGF-β₁, transforming growth factor beta1; PDGF, platelet derived growth factor.

Table 1

Characteristics of the patients from two asthma groups

Characteristic	Acute asthma group (n = 23)	Stable asthma group (n = 18)	Controls (n = 15)	P-value
Age (yr)	10.7 ± 2.8 (6-16)	9.4 ± 1.3 (7-12)	10.1 ± 2.6 (8-12)	0.21
Male sex	18 (72)	14 (70)	8 (53)	0.58
Severity of asthma score	2 (1-3)	2 (1-3)	NA	0.33
Duration of asthma (yr)	3.7 ± 1.5 (1-7)	3.8 ± 1.8 (2-7)	NA	0.87
Atopic sensitization	20 (87)	16 (89)	NA	0.72
Total serum IgE (kU/L)	479.0 ± 327.4	365.8 ± 211.6	NA	0.65
Blood eosinophils (mL)	786.7 ± 506.8	487.9 ± 249.6	-	0.09
Blood neutrophils (mL)	9,466.7 ± 3,385.2	7,800.2 ± 1,791.3	-	0.23
Lung function test			ND
FEV₁ %predicted	101.7 ± 17.2	102.4 ± 9.5		0.91
FEV₁/FVC %predicted	97.5 ± 10.4	100.2 ± 7.2		0.45
FEF_25%-75% %predicted	86.9 ± 34.6	85.6 ± 17.2		0.78
PC₂₀ (mg/mL)	12.3 ± 9.2	6.8 ± 5.9		0.12

Values are presented as mean±standard deviation (range), number (%) or median (range).

NA, not applied, ND, not determined; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; PC₂₀, provocative concentration of methacholine causing a 20% drop in FEV₁.

Table 2

Correlation between clinical parameters and serum levels of growth factors, YKL-40, and clusterin in acute asthma group

Variable	Correlation coefficient (r)
Variable	VEGF	TGF-β₁	PDGF-BB	YKL-40	Clusterin
Age	0.09	0.1	0.27	-0.08	0.27
Duration of asthma	-0.09	-0.29	0.13	0.17	-0.31
Asthma severity	0.51^*	-0.45	-0.28	0.34	-0.26
Symptom score during admission	-0.13	0.01	0.13	0.03	0.19
Total serum IgE	0.05	-0.35	-0.12	0.44	0
Blood eosinophils	0.32	0.01	0	0.22	-0.16
Blood neutrophils	0.13	0.13	-9.27	0.26	-0.21
Lung function
FEV₁ %predicted	0.19	-0.44^†	-0.31	0.03	-0.24
FEV₁/FVC %predicted	-0.01	-0.01	-0.12	-0.19	-0.26
FEF_25%-75% %predicted	0.18	-0.27	-0.31	0.07	-0.09
LogPC₂₀ (mg/mL)	0.22	-0.06	0.08	0.13	0.28

VEGF, vascular endothelial growth factor; TGF-β₁, transforming growth factor beta1; PDGF, platelet derived growth factor; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; PC₂₀, provocative concentration of methacholine causing a 20% drop in FEV₁.

^*P=0.03. ^†P=0.06.

Table 3

Correlation between clinical parameters and serum levels of growth factors, YKL-40, and clusterin in stable asthma group

Variable	Correlation coefficient (r)
Variable	VEGF	TGF-β₁	PDGF-BB	YKL-40	Clusterin
Age	-0.09	0.44	0.36	-0.30	-0.23
Duration of asthma	-0.14	-0.44	0.14	-0.59	0.16
Asthma severity	-0.13	0.06	0.56	-0.29	-0.13
Symptom score during admission	-0.39	-0.33	-0.14	-0.74	-0.25
Total serum IgE	-0.22	-0.39	-0.33	-0.16	-0.05
Blood eosinophils	0.15	-0.53	0.19	0.38	0.22
Blood neutrophils
Lung function
FEV₁ %predicted	0.37	-0.63^*	0.27	-0.28	0.29
FEV₁/FVC %predicted	0.19	-0.26	0.04	0.06	0.17
FEF_25%-75% %predicted	0.01	-0.67^*	-0.26	0.22	0.44
LogPC₂₀ (mg/mL)	0.12	-0.48	0.19	0.44	0.36

^*P=0.04.

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ORCID iDs: Hai Lee Chung
https://orcid.org/http://orcid.org/0000-0002-5364-5318
Similar articles

Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

Abstract

Purpose

Methods

Results

Conclusion

Figures and Tables

Fig. 1

Serum VEGF (A), TGF-β1 (B), PDGF-BB (C), YKL-40 (D), and clusterin (E) levels in acute and stable asthma groups, and controls. VEGF, vascular endothelial growth factor; TGF-β1, transforming growth factor beta1; PDGF, platelet derived growth factor.

Table 1

Characteristics of the patients from two asthma groups

Table 2

Correlation between clinical parameters and serum levels of growth factors, YKL-40, and clusterin in acute asthma group

Table 3

Correlation between clinical parameters and serum levels of growth factors, YKL-40, and clusterin in stable asthma group

References

Serum VEGF (A), TGF-β₁ (B), PDGF-BB (C), YKL-40 (D), and clusterin (E) levels in acute and stable asthma groups, and controls. VEGF, vascular endothelial growth factor; TGF-β₁, transforming growth factor beta1; PDGF, platelet derived growth factor.