Background: Small airway dysfunction (SAD) is a common problem in childhood asthma patients despite of asthma control therapy. The effectiveness and mechanism of allergen specific immunotherapy(AIT) on small airway dysfunction in children with asthma remains unclear. The purpose of this study is to investigate the the effectiveness of AIT on SAD and mechanism underline with special focus on basophil. Methods: 65 mild to moderate asthma children under regular ICS treatment for more than one year, but their FEF 75 remained below the 65% of predicted and with positive results of serum Der p or der f were enrolled. Asthma children underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 6 months. Asthma control and lung function were evaluated every three months during HDM SCIT treatment. Basophil activation test was carried out before and after HDM SCIT treatment. RNA-sequence were performed in isolated basophil from peripheral blood after 6 mionths of HDM SCIT treatment followed by GO term and KEGG pathway enrichment analysis between patients with or without HDM SCIT treatment. Results: The patients’ childhood asthma control test(C-ACT) scores have risen above the baseline value after 3 and 6 months’ treatment. The percentage of patients with complete asthma control was also increased from 52.4% to 75.8% (after 3 months of AIT treatment) and 73.7% (after 6 months of AIT treatment). Meanwhile, the percentage of uncontrolled asthmatic patients (C-ACT score＜20) dropped from 9.52% to 3 % and 0% after 3 and 6 months’ treatment of AIT, respectively. AIT treatment also improved lung function parameters such as FEV 1/FVC, FEF 75, FEF 50 and MMEF after the first 3 months’ therapy (p＜0.05). FEF 75 values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 65.56 ± 2.89 % and 71.89 ± 2.64 % after 3 months’ and 6months’ therapy, respectively). 24 of 32 patients were out of SAD after 6 months’ treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophil revealed that downregulated genes mainly involved in immune cell activation, antigen presenting procedure and Th cell differentiation. Conclusions: Our current study demonstrated that HDM AIT not only improved asthma symptom and clinic parameters, but also increased lung fuction parameters, especially improved SAD measured by FEF 75, FEF 50 and MMEF. We also demonstrated that HDM AIT reduced basophil activity. RNA-sequence of basophil revealed the inhibiton of phagocytosis and phagosome pathway which is required for the APC function of basophils and therefore may affect the polarization of Th2 cell differentiation. However, further in vivo and animal study are required to confirm those results.

Objective: To establish the predicted value of lung function determined by impulse oscillometry (IOS) in children (4~17 years old) in China. Methods: A total of 6270 healthy children aged 4 to 17 in Shanghai were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory total impedance (Zrs), response frequency (Fres), viscosity resistance (Rrs) and elastic resistance (Xrs) at various oscillation frequencies, and the indexes above were analyzed. The stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different genders. Results The median age of 6270 children (3345 boys and 2925 girls) was 10 years, ranging from 4 to 17 years. The differences in the main IOS parameters between different age and height groups are statistically significant regardless of sex (P<0.05). The values of Z5, R5, R20, and Fres decreased with the increase of age and height, while X5 increased with the increase of age and height. The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of regression coefficient was the largest). Conclusions: The study revealed the normal predicted value of pulmonary function by IOS in healthy children in China. In the evaluation of the results of the lung function measurements, the use of this predicted value equation is more in line with the characteristics of Chinese children than that of foreign countries. Key words: impulse oscillometry; respiratory function test; normal predicted value; child

Background：Wheezing is an important respiratory symptom in the diagnosis of asthma. However, wheezing is common in children and often related to viral infection. This and the lack of reliable biological indicators for asthma create difficulty in diagnosing asthma early in children. Objective: In this study, the levels of CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children with different diagnostic outcomes were investigated to determine correlation with a diagnosis of asthma and to assess their potential clinical value as a biological indicator for this disease. Methods: A prospective study was performed with a cohort of wheezing children aged 3 months to 6 years hospitalized in the Division of Pulmonary Pediatrics at Shanghai Xinhua hospital and Shanghai children’s medical center affiliated to Shanghai Jiao Tong University School of Medicine from July 2017 to March 2018. After inclusion, the level of serum IgE, presence of allergen-specific serum IgE (sIgE) and proportion of circulating CD4+CCR6+CRTh2+ memory Th2 cells were counted. In addition, the patients’ personal and family histories of allergic disease were acquired by questionnaire. The children were followed up annually over 2 years by telephone call with a guardian to record whether the child had been diagnosed with asthma. The accuracy of an increased proportion of CD4+CCR6+CRTh2+ memory Th2 cells as an indicator of asthma was assessed. Results: A total of 43 children completed follow-up. The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children diagnosed with or without asthma was 1.2%(0.8%~2.9%) and 0.6%(0.1%~0.9%), respectively, and was significantly higher in children diagnosed with asthma (P<0.01). The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in atopic children was also significantly higher in children diagnosed with asthma than in children without asthma, at 1.3%(0.8%~2.9%) and 0.6%(0.3%~1.0%), respectively, (P<0.01). Furthermore, the level of serum IgE was significantly higher in children with asthma (P<0.05). Logistic regression analysis indicated that the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells were independent risk factors for asthma. The area under the receiver operating characteristic curve (ROC) was 0.922. There was no significant difference in the positive rate of memory Th2 cells in the context of allergic rhinitis (AR) or atopic dermatitis (AD) (P>0.05). Conclusion: Our exploratory study found that an increase in the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells could be used as a biological indicator for early diagnosis of asthma, especially in predicting the risk of asthma in atopic children.