Objective To construct a nomogram prediction model for adverse reactions of mite sublingual immunotherapy(SCIT)in children with allergic asthma,and to evaluate and validate it.Methods Clinical data of children with allergic asthma who were managed by mite SCIT in Department of Pediatrics,the Second Hospital of Tianjin Medical University were retrospectively analyzed.According to the adverse reactions in the initial treatment stage of SCIT,they were divided into adverse reaction group and no adverse reaction group,which together formed the modeling group.Through univariate logistic regression analysis and multivariate logistic regression analysis,independent risk factors were screened out.Then construct the prediction model,draw a nomogram,eventually evaluate and validate the model.Results A total of 350 children were included,including 176 in the adverse reaction group and 174 in the no adverse reaction group.Univariate logistic regression analysis was performed on the baseline data of the children in the modeling group,and the results were as follows.Gender,age,number of asthma exacerbations in the past 1 year,percentage of eosinophils(EOS%),forced expiratory volume in the first second in percent predicted values(FEV1%pred),total IgE(tIgE),dermatophagoides pteronyssinus(Der p)sIgE,dermatophagoides farinae(Der p)sIgE,and the number of other inhaled allergenic species were the risk factors of SCIT-related adverse reactions(all P<0.1).These were included in the multivariate logistic regression analysis,and the results showed that:age,the number of asthma exacerbations in the past 1 year,tIgE,Der p sIgE,Der f sIgE,and the number of other inhaled allergen species were independent risk factors(all P<0.05).Based on the results,nomogram was drawn in R language.Model evaluation by receiver operating characteristic curve showed an area under curve of 0.877,a predictive model sensitivity of 73.9%,and a specificity of 90.8%.The predicted probability was consistent with actual probability of occurrence.The model has good prediction performance.Conclusions Age,number of asthma exacerbations in the past 1 year,tIgE,Der p sIgE,Der f sIgE,and the number of other inhaled allergen species were independent risk factors for adverse reactions to mite SCIT in children.The nomogram drawn in this study has good predictive value.

Allergen immunotherapy(AIT)is an effective treatment for allergic diseases that have been used for more than a century.At present, AIT is administered in two main ways: subcutaneous immunotherapy(SCIT)and sublingual immunotherapy(SLIT), which aims to induce immune tolerance to allergens and provide long-term clinical benefit to patients.The effectiveness of AIT has been confirmed and the research on its mechanism has been deepened, and AIT combined with biological agents has been widely used in clinical practice.

Objective: To investigate the efficacy and safety of Dupilumab in the treatment of moderate to severe atopic dermatitis（ AD） in children. Methods:A retrospective analysis was used to include 17 children with moderate-to-severe AD who received dupilumab for 16 weeks at the pediatric asthma and allergy-specific clinic of the Second Hospital of Tianjin Medical University from April 2021 to October 2022. Changes in various AD-related clinical assessment scales and clinical indicators of allergic co-morbidity,peripheral blood eosinophil count（ EOS）,and total serum IgE（ T-IgE） levels were compared before and after treatment.The proportion of children achieving EASI50 and EASI90（ ≥50% and ≥90% reduction in eczema area and severity index from baseline to 16 weeks）,and the proportion achieving an IGA（ Investigator′s Overall Assessment） score of 0 or 1（ rash clearance or almost clearance） during the treatment period was assessed.The adverse reactions and adverse events during treatment were observed. Results:Compared with baseline,the AD-related assessment scales showed a significant decrease 2 weeks after the first dupilumab injection（ all P＜0.01）;the proportion of patients achieving EASI50,EASI90 and IGA scores of 0 or 1 increased significantly immediately after 8 weeks of treatment. After 16weeks of dupilumab treatment,the patients′ EOS levels increased overall from baseline and serum T-IgE levels decreased from baseline in 5 patients,but the differences were not statistically significant. Children with combined asthma or allergic rhinitis（ AR） had significant improvements in Childhood Asthma Control Test/Asthma Control Test（ C-ACT/ACT）,Asthma Control Questionnaire（ ACQ）,visual analog scale（ VAS） scores for rhinitis,exhaled nitric oxide（ FeNO） levels and inhaled corticosteroids（ ICS） dose decreased significantly from baseline,and the forced expiratory volume in the first second（ FEV1） increased from baseline（ all P＜0.05）. Two children with combined food allergy had improvement of AD rash and itching aggravation induced by previous consumption of allergic food.Conjunctivitis developed in 3 cases during treatment.Conclusion:Dupilumab treatment can significantly improve the clinical symptoms of moderate and severe AD children and their allergic comorbidities,reduce the level of FeNO and ICS dose,improve lung function,and may reduce the level of serum T-IgE. During the treatment,there were few adverse reactions,mainly mild to moderate conjunctivitis,with good safety.

Objective:To analyze the efficacy and safety of Omalizumab (OMA) combined with allergen immunotherapy (AIT) on children with allergic asthma.Methods:Clinical data of 43 children with allergic asthma from the Second Hospital of Tianjin Medical University between August 2018 and October 2022, who were managed by OMA combined with double mite subcutaneous immunotherapy (SCIT) were retrospectively analyzed, including 30 males and 13 females with the age of 5-15 years.Twenty children with allergic asthma who were managed by the monotherapy for SCIT during the same period, including 16 males and 4 females with the age of 4-13 years were included in the control group(group1: conventional immunotherapy; group2: cluster immunotherapy). Among the 43 cases managed by OMA combined with SCIT, 20 were treated with OMA, followed by AIT (OMA-AIT group), and 23 were treated with AIT, followed by OMA (AIT-OMA group). Notably, 6 cases in AIT-OMA group who were additionally given OMA due to the difficulty in increasing doses were subgrouped in AO1 group, and 17 who were additionally given OMA due to poor control of asthma or comorbidities during the course of AIT and frequent adverse events were subgrouped in AO2 group.The number of asthma exacerbations within 1 year and during the combination therapy, the Childhood Asthma Control Test/Asthma Control Test (C-ACT/ACT) findings, the Visual Analogue Scale (VAS) for grading rhinitis, inhaled corticosteroid (ICS) dosage converted to budesonide equivalent, the Total Medication Score (TMS), comorbidities, lung function [percent-predicted forced expiratory volume in 1 second(FEV 1% pred), percent-predicted peak expiratory flow(PEF%pred), percent-predicted maximal mild-expiratory flow(MMEF%pred)], exhaled nitric oxide (FeNO), completion of the initial SCIT and adverse effects [local adverse reactions (LRs) and systemic adverse reactions (SRs)] were analyzed for assessing the efficacy and safety of OMA combined with AIT on children with allergic asthma.The t-test of two independent samples was used for comparison of measurement data that followed normal distribution.Wilcoxon′s test was used for non-normally distributed between-group comparisons.The χ2 test was used for the between-group comparison of counting data. Results:(1)Baseline comparison showed that the male ratio (17/20 cases vs.13/23 cases) and the proportion of moderate-to-severe persistent asthma (18/20 cases vs.18/23 cases) in the OMA-AIT group were significantly higher than those of the AIT-OMA group (all P<0.05). (2)Efficacy: ①In OMA-AIT group, all children reached the AIT maintenance treatment stage successfully after combination therapy.At the maintenance treatment stage, the C-ACT/ACT, VAS and TMS scores(26.0±1.25 vs.24.55±2.28, 1.50±1.24 vs.2.55±1.70, 3.60±1.47 vs.5.45±1.19)were significantly improved from baseline(all P<0.05). There were no significant differences in lung function indexes FEV 1%pred, PEF%pred, and MMEF%pred ( P>0.05), and FeNO level did not change significantly than baseline.After the combination treatment, ICS dosage significantly decreased from 240.00 (160.00, 380.00) μg/d at baseline to 140.00 (80.00, 300.00) μg/d ( P<0.05). Comorbidities, including allergic rhinitis, food allergy, atopic dermatitis and angioedema were improved.Five cases (25.00%) had once asthma exacerbation during the treatment.The duration of maintenance dose of conventional (22.70±7.10 vs.15.20±1.32) and cluster immunotherapy (13.00±4.97 vs.7.30±1.06) were longer than those of the corresponding control group(all P<0.05). ②AIT-OMA group: In AO1 group, the C-ACT/ACT score were improved from baseline( P<0.05), and VAS score, TMS score decreased from 3.00(1.75, 3.00), (4.67±1.97) points at baseline to 1.00(0, 1.00), (2.83±1.60) points by the maintenance dose in AO1 group (all P<0.05). There were no significant differences in the FEV 1%pred, PEF%pred, MMEF%pred and FeNO compared with baseline in AO1 group.ICS dosage in AO1 group significantly decreased from (180.00±78.99) μg/d at baseline to (88.88±26.23) μg/d ( P<0.05). In AO2 group, the C-ACT/ACT, VAS and TMS scores at the completion of OMA treatment[26.53±0.94 vs.25.06±2.05, 1.00 (0, 2.00) vs.2.00(2.00, 3.50), 3.41±0.94 vs.5.53±1.23]were significantly improved from baseline (all P<0.05). PEF%pred[(106.47±22.37)% vs.(94.47±26.39)%] significantly increased than baseline ( P<0.05), and the remaining lung function indexes and FeNO were not significantly improved.ICS dosage significantly decreased from 240.00(160.00, 400.00) μg/d at baseline to 80.00 (20.00, 160.00) μg/d ( P<0.05). During the combination treatment, 1 case (5.88%) had once asthma exacerbation, and all 8 cases with food allergy or atopic dermatitis or conjunctivitis had improved comorbidities.(3)Safety: adverse events during OMA injection were not reported.①In OMA-AIT group, a total of 165 OMA injections were performed in the initial treatment stage of the conventional immunotherapy group, with 13 (7.88%) reported LRs and 2 (1.21%) grade-1 SRs.A total of 143 OMA injections were performed in the initial treatment stage of the cluster immunotherapy group, with 19(13.29%) reported LRs and none of SRs.②In AIT-OMA group, there were 6 cases of adverse events in the initial treatment stage of AIT who were successfully reached the maintenance treatment stage after the addition of OMA in AO1 group.In AO2 group, children who were additionally given OMA due to adverse events in the maintenance treatment phase did not report adverse events during the combination therapy. Conclusions:OMA combined with AIT not only expands the scope of AIT, improves allergic and asthma symptoms in children, reduces the use of drugs, but also enhance the safety of AIT and compliance, reduces adverse events during AIT treatment, and even shortens the time of initial treatment.