Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma

Abstract

Background: Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma.

Methods: We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls.

Results: Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age.

Conclusions: Age-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma.

Keywords: Age; Asthma; Childhood; Cytokine; Virus detection.

Fig. 1

Virus detection in acute exacerbations of childhood asthma. Among the 88 samples from asthma exacerbation cases, rhinovirus was detected in 30; RS virus in 18; enterovirus in 9; human coronavirus in 2, human bocavirus in 1, influenza virus in 1, human parainfluenza virus in 1, ≥2 viruses in 9; and no viruses were found in 17.

Fig. 2

Monthly (A) and age-dependent (B) changes of virus detection in acute exacerbations of asthma. (A) Two-thirds of the patients were hospitalized or treated for asthma attacks between September and December. RS viruses were frequently detected from May to June and from November to December. Enteroviruses were dominant in September. In contrast, rhinoviruses were detected almost all year round. (B) More than half the patients with acute exacerbations of asthma were <3-year-old. Among the three major detected viruses, rhinovirus, RS virus, and enterovirus, enteroviruses were dominant in patients aged ≥3 years. However, there was no change in the levels of rhinoviruses and RS viruses between the two age groups.

Fig. 3

Peripheral eosinophils counts, serum ECP, and cytokines/chemokines in virus-induced acute exacerbation of asthma and controls. Among the concentrations of serum ECP and 27 cytokines/chemokines, ECP, IL-5, and IP-10 were significantly elevated in virus-induced asthma compared with controls. In contrast, only IL-1β was significantly lower in asthma cases than in controls. A horizontal bar represents the median. Data were analyzed using the Mann–Whitney U test. *p < 0.05; **p < 0.01; ***p < 0.001.

Fig. 4

Comparison between peripheral eosinophils counts, serum ECP, and cytokines/chemokines in virus-induced acute exacerbations of asthma between patients aged <3-year-old and those aged ≥3 years, as well as controls. ECP serum values were significantly higher in virus-induced asthma in patients aged ≥3 years than in those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients aged <3 years than in those aged ≥3 years. The median is represented by horizontal bars. Data were analyzed using the Kruskal–Wallis test followed by Dunn's multiple comparison test. *p < 0.05; **p < 0.01; ***p < 0.001.

Fig. 5

Correlation between age and several parameters in virus-induced acute exacerbation of asthma. The production of serum ECP and IL-5, but not eosinophil count, correlated significantly with age. Serum IP-10 was inversely correlated with age. Data were analyzed using the Spearman rank correlation coefficient analysis.