Background

Asthma is the most common chronic respiratory disease in childhood. However, it is quite difficult to make a prompt diagnosis of asthma in a child 5 years and younger, partly due to a lack of objective diagnostic means. Our previous studies on susceptibility gene of asthma showed that a gene-gene interaction among 4 single nucleotide polymorphisms including IL13 rs20541 and IL4 rs2243250, ADRB2 rs1042713 and FcER1B rs569108 had a predictable role for asthma in wheezing children.

Objective

The study was aimed to further investigate the predictive effects of the four-loci interaction model in Chinese preschool children with asthma.

Methods

A total of 212 wheezing children aged 6 months to 5 years were enrolled and followed up for at least one year at Shanghai Xinhua Hospital between Dec 2014 and Mar 2016. Clinical data and lab findings of atopy were collected. All the children were divided into the high-risk group and the low-risk group according to genotypes of the four-loci interaction model. The differences of clinical features were compared between the two groups. The predictive effects for asthma were analyzed among asthma predictive index (API), 2015 Canadian Diagnostic Criteria for Asthma in Preschoolers and our four-loci interaction model.

Results

Of all the enrolled 212 children, 117 (55.2%) were assigned into the high-risk group and 95 (44.8%) were the low-risk group. Compared with the low-risk group, the high-risk group had more yearly episodes of wheeze and a higher level of blood eosinophilia. More children in the high-risk group presented with afebrile wheeze, eczema and positive food or aero allergens and had a history of tobacco exposure. If the asthma-predictive effect of positive API was considered as 1, the four-loci interaction model had a sensitivity of 77.2%, a specificity of 80.0% and an AUC area of 0.786 with a modest consistency (P= 0.22, Kappa= 0.49), while the Canadian criteria had a sensitivity of 97.8%, a specificity of 53.3% and an AUC area of 0.539 with a low consistency (P< 0.01, Kappa= 0.265).

Conclusions

The four-loci interaction model is associated with the phenotypes of wheezing in Chinese preschoolers. It has a consistent predictive effect with API for asthma and is more specific than the Canadian criteria in the diagnosis of asthma, which indicates that the four-loci interaction model may be developed as a new objective predictive tool for asthma in Chinese children 5 years and younger.