Pathogens and Pathogenesis in Wheezing Diseases in Children Under 6

Abstract

Few studies have comprehensively assessed the roles of cytokine production in wheezing pathogenesis. Therefore, we undertook this study to determine the association between wheezing episodes and cytokines, and to provide further information on this topic. Firstly, we retrospectively collected I176 children, including 122 subjects with first wheezing and 54 subjects with recurrent wheezing, to analyze the etiology and clinical characteristics of children with wheezing diseases. Then, we collected 52 children with wheezing diseases and 25 normal controls to detect the expression of interferon-γ (IFN-γ), interleukin-4 (IL-4), IFN-γ/IL-4, IL-17A, IL-17E, IgE, matrix metalloproteinase-3 (MMP-3), and MMP-9 in serum or plasma. The results showed that boys under 3 years old with history of allergies were more likely to develop wheezing diseases. In our cohort, M. pneumoniae caused a greater proportion of wheezing in children than expected. The expression of IgE [18.80 (13.65-31.00) vs. 17.9 (10.15-21.60)], IL-4 [24.00 (24.00-48.00) vs. 23.00 (9.50-27.00)], IFN-γ [70.59 (41.63-116.46) vs. 49.83 (29.58-81.74)], MMP3 [53.40 (20.02-128.2) vs. 30.90 (13.80-50.95)], MMP9 [148.10 (99.30-276.10) vs. 122.10 (82.20-162.35)], IL-17A [80.55 (54.46-113.08) vs. 61.11 (29.43-93.87)], and IL-17E [1.75 (0.66-2.77) vs. 1.19 (0.488-2.1615)] were significantly increased in the wheezing group (p<0.05) compared to normal controls, while the level of IFN-γ/IL-4 had no significant difference between the two groups (1.24 ± 1.88 vs 0.68 ± 0.74, p>0.05). There was altered cytokine production in children with wheezing diseases which was quite similar to asthma pathogenesis. Sex, age, pathogen infection, and inflammation in our study were also risk factors for wheezing diseases.

Keywords: IFN-γ; IL-17; IL-4; IgE; MMP; infant; wheezing.

Figure 1

Flowchart of grouping and analysis. Firstly, we collected 176 patients from Xiangya Hospital and grouped as first wheezing (n = 122) and recurrent wheezing (n = 54) to analyze clinical characteristics. Then we collected 52 patients from Xiangya Hospital and Hunan Children’s Hospital and 25 normal control from Xiangya Hospital to test cytokines.

Figure 2

The pathogen analysis of the wheezing children (A) For 176 patients, virus, MP, bacterial, fungus, and mixed are causes of wheezing, but nearly half of the children’s etiology were unknown. (B) Fifty-five patients were infected with a virus and the top three virus were coxsackie virus, RSV, and CMV. (C) Twenty-nine patients were infected with bacteria and common bacteria were streptococcus pneumoniae, klebsiella pneumoniae, staphylococcus, and E.coli. MP, mycoplasma pneumoniae; RSV, respiratory syncytial virus; CMV, cytomegalovirus; E.coli, Escherichia coli.