孟鲁司特属于白三烯受体调节剂，临床上孟鲁司特防治年幼儿反复喘息的疗效存在个体差异。部分反复喘息年幼儿以后将发展为哮喘，故哮喘易感基因SNPs可能可以预测反复喘息年幼儿日后的哮喘发生情况，白三烯通路基因多态性可能会影响孟鲁司特治疗的效果。本项目采用队列研究，拟选取浙南地区1~6岁因反复喘息于2021年1月1日~2022年12月31日至我院儿童呼吸科住院治疗的500例汉族儿童为研究对象，运用MALDI-TOF技术分析浙南地区汉族反复喘息年幼儿中哮喘易感基因及白三烯通路基因中常见25个SNPs分布及单倍型分布，建立哮喘预测模型；通过基因型分层观察基因多态性与孟鲁司特按需治疗一年疗效的关系，构建孟鲁司特治疗反复喘息年幼儿的疗效预测模型；研究SNPs影响孟鲁司特治疗反复喘息年幼儿疗效的可能机制。本课题对年幼儿反复喘息的哮喘预测及其孟鲁司特个体化治疗具有重要意义。

Montelukast is one of the most common Leukotriene receptor antagonists in treatment of children with wheezing diseases. However, there is individual differences on the efficacy of montelukast in young children with re-current wheeze. Some of the children with recurrent wheezing will develop to asthma, thus studies suggest it may be partly caused by the single nucleotide polymorphisms (SNPs) on asthma susceptibility genes. And the SNPs on the leukotriene pathway genes might influence the efficacy of montelukast in children with recurrent wheezing. According to the previous study, We found rs1042713, rs2305089, rs2540487, rs2712807, rs28364072, rs320995, rs4980524 and rs730012 were associated with the efficacy of Budesonide/Fomoterol 80/4.5 inhaler therapy for 12 weeks in children with asthma from South Zhejiang of China..The current study is designed as a cohort study. The participants will be screened from January 1, 2021 to December 31, 2022 in 1~6 years old patients from South Zhejiang, who hospitalized with re-current wheeze in Respiratory Department of the Second Affiliated Hospital﹠Yuying Children’s Hospital of Wenzhou Medical University. The frequency of wheeze is defined as more than twice without airway malformation, congenital heart disease, tuberculosis infection, bronchopulmonary dysplasia, airway foreign bodies and protracted bacterial bronchiolitis. 500 cases of Han children with re-current wheeze will be enrolled to the study. Twenty-five SNPs genes of asthma susceptibility and leukotriene pathway will be analyzed by MALDI-TOF technique. The frequency of genotype and haplotype analysis will be performed in young children with re-current wheeze children. The association between the twenty-five SNPs and clinical phenotype of the young children will be analyzed. All participants will recevie intermittent montelukast therapy at each wheeze episode (12 weeks course per wheeze), and they will be followed up for one year. The primary outcome is number of children diagnosed asthma on year of 3 age and year of 7 age, the unscheduled medical attendances for wheezing when receiving the intermittent montelukast therapy of one year. A model for predicting asthma and a model for predicting efficacy of leukotriene modifiers in the treatment of young children with recurrent wheezing will be established. And functional experiments of positive SNPs will be studied in primary airway smooth muscle cells and airway epithelial cells of OVA sensitization mice in vitro . This study will be a great significance to montelukast in individual treatment of re-current wheezing in young children.