Clinical characteristics of interferon-gamma-inducible protein of 10 kDa in children with wheezing

Beom Joon Kim; Kil Seong Bae; Hwan Soo Kim; Yoon Hong Chun; Jong-Seo Yoon; Hyun Hee Kim; Jin Tack Kim

doi:10.4168/aard.2016.4.3.174

Journal List > Allergy Asthma Respir Dis > v.4(3) > 1059175

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Kim, Bae, Kim, Chun, Yoon, Kim, and Kim: Clinical characteristics of interferon-gamma-inducible protein of 10 kDa in children with wheezing

Original Article

Allergy, Asthma & Respiratory Disease 2016; 4(3): 174-180.

Published online: 31 May 2016

DOI: https://doi.org/10.4168/aard.2016.4.3.174

Clinical characteristics of interferon-gamma-inducible protein of 10 kDa in children with wheezing

Beom Joon Kim, Kil Seong Bae, Hwan Soo Kim, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim

, Jin Tack Kim

Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Correspondence to: Hyun Hee Kim, Department of Pediatrics, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Cheonbo-ro, Uijeongbu 11765, Korea. Tel: +82-31-820-3580, Fax: +82-31-821-3108, hhkped@catholic.ac.kr

Received 4 August 2015 Revised 12 October 2015 Accepted 13 October 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/4.0/).

Abstract

Purpose

Recent studies have shown that interferon-gamma-inducible protein of 10 kDa (IP-10/CXCL10) levels is increased in acute bronchiolitis and asthma. The aim of this study was to examine the levels of IP-10 in children with wheezing and whether it correlates with other clinical variables.

Methods

A total of 62 subjects children were hospitalized for lower respiratory tract infection with wheezing and visited the Emergency Department due to an acute exacerbation of asthma. IP-10 levels were measured using enzyme-linked immunosorbent assay in the serum collected at admission. Serum IP-10 levels were evaluated for the relationships with age, sex, blood eosinophils counts, acute phase reactant, allergic sensitization, history of wheezing, and chest X-ray findings.

Results

Age showed a significant negative correlation with serum IP-10 levels (P=0.002). The serum levels of IP-10 were also significantly increased in patients with pneumonic infiltration on X-rays compared to those with normal or hyperinflation (P<0.009). There was no significant difference in the serum IP-10 level according to the other factors, including allergic sensitization.

Conclusion

Serum IP-10 is significantly associated with inflammation of the lung and age, but not with allergic inflammation.

Keywords: Interferon-gamma-inducible protein of 10 kDa, Wheezing, Child

Figures and Tables

Table 1

General characteristics of the patients (n=62)

Characteristic	Value
Age (yr)	4 (0.5-14)
<1	3
1-5	35
6-10	18
≥11	6
Sex
Male	39 (62.9)
Female	23 (37.1)
Symptoms
Fever	12 (19.4)
Rhinorrhea	32 (51.6)
History of allergy^*	44 (71.0)
Laboratory results
White blood cell (×10³/µL)	11,170 (4,570-30,530)
Neutrophil (%)	66.0 (11.1-93.6)
Eosinophil (%)	2.7 (0-21.0)
ANC (cells/µL)	7,184 (670-28,576)
ESR (mm/hr)	11.5 (0-69)
C-reactive protein (mg/dL)	0.43 (0-10.38)
Total IgE (IU/mL)	323 (5.8-3,440)
IP-10 (pg/mL)	1,070 (203-7,606)

Values are presented as median (range) or number (%).

ANC, absolute neutrophil count; ESR, erythrocyte sedimentation rate; IP-10, interferon-gamma-inducible protein of 10 kDa.

^*History of allergy includes asthma, atopic dermatitis, allergic rhinitis, food allergy.

Table 2

Associations of IP-10 with factors in children with wheezing

Variable	Age (yr)	No. of cases (n=62)	IP-10 (pg/mL)	P-value
Sex				0.109
Male	4 (0.6-12)	39 (62.9)	948 (203-4,656)
Female	5 (0.5-14)	23 (37.1)	1,392 (217-7,606)
Allergic sensitization				0.388
No sensitization	4 (0.5-14)	21 (33.9)	1,061 (256-4,656)
Sensitization	5 (3-12)	41 (66.1)	1,079 (203-7,606)
Previous wheezing history				0.907
First wheezer	4 (0.9-10)	12 (19.3)	954 (279-4,656)
Past wheezer	5 (0.5-12)	41 (66.1)	998 (203-3,567)
Eosinophils count				0.092
<4	4 (0.5-12)	37 (59.7)	1,275 (203-7,606)
≥4	7 (3-14)	23 (37.1)	963 (217-2,678)
Chest X-ray				0.009
Normal	7 (0.5-14)	31 (50.0)	925 (203-3,860)
Hyperinflation	4 (3-12)	19 (30.6)	1,283 (279-2,401)
Pneumonic infiltration	3 (0.9-11)	12 (19.4)	2,558 (684-7,606)

Values are presented as median (range) or number (%).

IP-10, interferon-gamma-inducible protein of 10 kDa.

Table 3

Associations of inflammatory factors with chest X-ray findings

Variable	Normal		Hyperinflation		Pneumonic infiltration		P-value
Variable	Median (range)	No.^*	Median (range)	No.^*	Median (range)	No.^*	P-value
Eosinophil (%)	3.5 (0-13.2)	30	3.1 (0.1-21.0)	18	1.4 (0-7.4)	12	0.240
WBC (× 10³/µL)	10,790 (6,100-19,130)	29	12,150 (4,920-30,530)	17	7,875 (4,570-18,570)	12	0.129
ESR (mm/hr)	9.0 (0.0-69.0)	30	11.0 (0.0-53.0)	18	17.5 (7.0-55.0)	12	0.234
CRP (mg/dL)	0.2 (0.0-2.5)	31	0.6 (0.0-2.8)	19	0.2 (0.1-10.4)	12	0.185
ANC (cells/µL)	6,942 (1,634-16,281)	29	8,515 (1,338-28,576)	17	5,645 (670-14,967)	12	0.170

WBC, white blood cell; CRP, C-reactive protein; ANC, absolute neutrophil count; ESR, erythrocyte sedimentation rate.

^*Number of cases.

Table 4

Correlation between IP-10 and other inflammatory factors according to chest X-ray findings

Factor	Normal			Hyperinflation			Pneumonic infiltration
	No.^*	Coefficient	P-value	No.^*	Coefficient	P-value	No.^*	Coefficient	P-value
Eosinophil	30	-0.085	0.655	18	-0.350	0.154	12	-0.294	0.354
WBC	29	0.037	0.849	17	0.049	0.851	12	-0.573	0.051
CRP	31	0.112	0.548	19	0.007	0.977	12	-0.438	0.154
ESR	30	-0.218	0.247	18	-0.107	0.671	12	-0.014	0.965
ANC	29	0.083	0.669	17	0.059	0.822	12	-0.608	0.035

IP-10, interferon-gamma-inducible protein of 10 kDa; WBC, white blood cell; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ANC, absolute neutrophil count.

^*Number of cases.

Table 5

Correlation between IP-10 and factors in children with wheezing

Factor	IP-10 (n = 62)	Coefficient	P-value
Age (yr)	62	-0.380	0.002
WBC (× 10³/µL)	58	-0.167	0.211
Eosinophil (%)	60	-0.234	0.071
ANC (cells/µL)	58	-0.153	0.252
ESR (mm/hr)	60	-0.066	0.615
CRP (mg/dL)	62	0.074	0.569

IP-10, interferon-gamma-inducible protein of 10 kDa; WBC, white blood cell; ANC, absolute neutrophil count; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 6

Multiple regression analysis of IP-10 and factors in children with wheezing

Variable	Univariable			Multivariable
Variable	β	SE	P-value	β	SE	P-value
Allergic sensitization	-0.2393	0.2251	0.2922	-	-	-
Age	-0.1019	0.0315	0.0020	-0.0907	0.0377	0.0203
CXR: pneumonic infiltrarion	0.6606	0.2865	0.0247	0.6548	0.2870	0.0272
First wheezer	0.0977	0.2625	0.7114	0.0006	0.2478	0.9980
Eosinophil (> 4%)	-0.0281	0.0269	0.3011	0.0252	0.0264	0.3450

IP-10, interferon-gamma-inducible protein of 10 kDa; SE, standard error; CXR, chest X-ray.

References

1. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995; 332:133–138.

2. Suh DI, Koh YY. Early childhood wheezing: various natural courses and their relationship to later asthma. Korean J Pediatr. 2012; 55:259–264.

3. Wright AL. Epidemiology of asthma and recurrent wheeze in childhood. Clin Rev Allergy Immunol. 2002; 22:33–44.

4. Yu J, Yoo Y, Kang H, Koh YY. Bronchial hyperresponsiveness and atopy in 6-8 year old children according to the history of wheezing in early childhood. Korean J Pediatr. 2004; 47:873–878.

5. Gaillard EA, McNamara PS, Murray CS, Pavord ID, Shields MD. Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial. Clin Exp Allergy. 2015; 45:1384–1395.

6. Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011; 22:121–130.

7. Park MY, Kim SY, Hwang SH, Kim JE, Lee MK, Lee CH, et al. Preliminary study for elevated serum CXCL10 and CXCL11 in active pulmonary tuberculosis compared with the other pulmonary diseases. Tuberc Respir Dis. 2009; 66:205–210.

8. Medoff BD, Sauty A, Tager AM, Maclean JA, Smith RN, Mathew A, et al. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol. 2002; 168:5278–5286.

9. Miotto D, Christodoulopoulos P, Olivenstein R, Taha R, Cameron L, Tsicopoulos A, et al. Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in TH1- and TH2-mediated lung diseases. J Allergy Clin Immunol. 2001; 107:664–670.

10. Brasier AR, Victor S, Boetticher G, Ju H, Lee C, Bleecker ER, et al. Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines. J Allergy Clin Immunol. 2008; 121:30–37.e6.

11. Lai ST, Hung CH, Hua YM, Hsu SH, Jong YJ, Suen JL. T-helper 1-related chemokines in the exacerbation of childhood asthma. Pediatr Int. 2008; 50:99–102.

12. Tworek D, Kuna P, Młynarski W, Gorski P, Pietras T, Antczak A. MIG (CXCL9), IP-10 (CXCL10) and I-TAC (CXCL11) concentrations after nasal allergen challenge in patients with allergic rhinitis. Arch Med Sci. 2013; 9:849–853.

13. Cakebread JA, Haitchi HM, Xu Y, Holgate ST, Roberts G, Davies DE. Rhinovirus-16 induced release of IP-10 and IL-8 is augmented by Th2 cytokines in a pediatric bronchial epithelial cell model. PLoS One. 2014; 9:e94010.

14. Roe MF, Bloxham DM, Cowburn AS, O'Donnell DR. Changes in helper lymphocyte chemokine receptor expression and elevation of IP-10 during acute respiratory syncytial virus infection in infants. Pediatr Allergy Immunol. 2011; 22:229–234.

15. Zou LP, Xu XJ, Zhang Y, Wang W. Roles of CXCR3 on lymphocytes and IP-10 of peripheral blood in infants with bronchiolitis. Zhongguo Dang Dai Er Ke Za Zhi. 2015; 17:155–158.

16. Guilbert TW, Morgan WJ, Zeiger RS, Bacharier LB, Boehmer SJ, Krawiec M, et al. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol. 2004; 114:1282–1287.

17. Biancotto A, Wank A, Perl S, Cook W, Olnes MJ, Dagur PK, et al. Baseline levels and temporal stability of 27 multiplexed serum cytokine concentrations in healthy subjects. PLoS One. 2013; 8:e76091.

18. Kleiner G, Marcuzzi A, Zanin V, Monasta L, Zauli G. Cytokine levels in the serum of healthy subjects. Mediators Inflamm. 2013; 2013:434010.

19. Kato M, Suzuki K, Yamada Y, Maruyama K, Hayashi Y, Mochizuki H. Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma. Allergol Int. 2015; 64:S64–S70.

20. Tamayose M, Fujita J, Parrott G, Miyagi K, Maeshiro T, Hirata T, et al. Correlations between extent of X-ray infiltration and levels of serum C-reactive protein in adult non-severe community-acquired pneumonia. J Infect Chemother. 2015; 21:456–463.

21. Pickup CM, Nee PA, Randall PE. Radiographic features in 1016 adults admitted to hospital with acute asthma. J Accid Emerg Med. 1994; 11:234–237.

22. Farber D, Bauer CP, Hahn H. Radiologic findings and differential diagnosis of bronchial asthma in childhood. Radiologe. 1990; 30:319–323.

23. Ismail Y, Loo CS, Zahary MK. The value of routine chest radiographs in acute asthma admissions. Singapore Med J. 1994; 35:171–172.

24. Halaby C, Feuerman M, Barlev D, Pirzada M. Chest radiography in supporting the diagnosis of asthma in children with persistent cough. Postgrad Med. 2014; 126:117–122.

25. Sarris AH, Broxmeyer HE, Wirthmueller U, Karasavvas N, Cooper S, Lu L, et al. Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. J Exp Med. 1993; 178:1127–1132.

26. Antonelli A, Ferrari SM, Giuggioli D, Ferrannini E, Ferri C, Fallahi P. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev. 2014; 13:272–280.

27. Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, Yamada Y, et al. Different cytokine profile and eosinophil activation are involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing. Pediatr Allergy Immunol. 2011; 22(1 Pt 2):e87–e94.

28. Wark PA, Bucchieri F, Johnston SL, Gibson PG, Hamilton L, Mimica J, et al. IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations. J Allergy Clin Immunol. 2007; 120:586–593.

29. Lau S, Illi S, Sommerfeld C, Niggemann B, Bergmann R, von Mutius E, et al. Multicentre Allergy Study Group. Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Lancet. 2000; 356:1392–1397.

30. Johnson JR, Wiley RE, Fattouh R, Swirski FK, Gajewska BU, Coyle AJ, et al. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Respir Crit Care Med. 2004; 169:378–385.

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ORCID iDs: Hyun Hee Kim
https://orcid.org/http://orcid.org/0000-0002-7196-2894
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