Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite-allergic children with asthma

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific-allergen immunotherapy, the efficacy of long-term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel-group, controlled study. Children with asthma aged 4-16 yr, sensitive to house dust mite (HDM) were followed up for a run-in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom-medication scores and lung function tests every 3 months, as well as skin-prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within-group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM-allergic children with asthma.     

Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D. pt.) in children

Safety and efficacy of sublingual (sublingual-swallow) immunotherapy (IT) with house dust mite extract were evaluated in 30 children (6 - 15_2/3 years of age) over the first 12 months of an ongoing study. The cumulative dose was 570 μg Der p I (five times that administered with subcutaneous therapy). Safety: One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness, questionably induced by the therapy. Five patients on active therapy and one patient on placebo reported minor local side effects. Efficacy: Pulmonary symptoms were reduced after 12 months in actively treated asthmatics, but this was not consistent with the lack of improvement in bronchial reactivity, skin sensitivity and specific IgG and IgG4 against D. pt. in this group. In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score. Specific IgE (D. pt. and D. f.) in creased significantly more in the active treatment group after 3 and 12 months. We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated, but there was no consistent clinical or immunological benefit compared to placebo.     

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.     

Atopy patch testing in children with asthma and rhinitis symptoms allergic to house dust mite

The atopy patch test (APT) is generally used to assess immunoglobulin E (IgE) mediated sensitization to allergens in patients with atopic dermatitis, but its diagnostic role in children with respiratory allergy is still controversial. The aim of the study was to evaluate APT with house dust mite (HDM) in children with asthma and rhinitis symptoms allergic to HDM and its relevance to skin prick test (SPT) diameters and specific IgE levels. The study population consisted of 33 children, aged 8-16 yr (median: 12 yr) with asthma and 30 children with allergic rhinitis in the same age range (median: 11 yr). All patients had positive SPT results and high serum specific IgE levels for Dermatophagoides pteronyssinus APT was performed on back skin of all patients with 200 index of reactivity (IR)/ml of D. pteronyssinus allergen extracts in petrolatum (Stallerpatch) and evaluated at 72 h. Of 63 patients, 16 (25%) showed a positive patch test result. APT with HDM showed 30% (10/33) positivity among the patients with asthma and 20% (6/30) positivity among the patients with allergic rhinitis. APT presented no significant correlation with age, SPT diameter, serum total and specific IgE levels for D. pteronyssinus, nasal provocation test or pulmonary function test results. Patch testing with HDM may partly identify mite sensitive children with respiratory allergy. Positive APT results may imply that delayed hypersensitivity reactions play a role in children with asthma and rhinitis allergic to HDM.     

Snail anaphylaxis during house dust mite immunotherapy

This study reports a 12-year-old girl who developed an anaphylactic reaction following snail ingestion during house dust mite (HDM) immunotherapy treatment. Radioallergosorbent (RAST) inhibition showed cross-reactivity between the two allergens, leading to consideration of HDM as the sensitizing agent. Children undergoing HDM immunotherapy treatment should be aware of the potential risks of hypersensitivity reactions to invertebrate foods.     

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??Objective To understand the dynamic changes of early clinical curative effect in children with asthma and allergic rhinitis who received the dust mite specific immunotherapy??and to discuss the influencing factors of the efficacy. Methods A total of 70 cases with mild or moderate persistent asthma combined with allergic rhinitis who received the dust mite specific immunotherapy combined with drug therapy between February 2012 and November 2012 in Beijing Children’s Hospital were adopted in the case-self-control study. Results Totally 54 cases completed treatment of 12 months. The clinical response rates to SIT ??effective cases?? at 3??6??9 and 12 months after SIT were 72.2%??39????75.9%??41????81.5%??44?? and 87.0%??47???? respectively. After one year of treatment??the average daily SMS and VAS score were all decreased ??5.28±2.28 vs. 2.87±1.96??5.59±3.35 vs. 4.04±3.68?? P??0.05??. PEF% pred was improved???95.41±15.18?? vs. ??99.24±16.24????P??0.05??. Conclusion The effective rate of SIT increases gradually with prolonged treatment. When children with asthma and allergic rhinitis received immunotherapy combined with drug therapy??the patients with higher baseline SMS??shorter asthma history and lower PEF%pred respond more effectively to SIT.     

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目的 探讨特异性免疫治疗变应性哮喘合并鼻炎的效果,分析特异性免疫治疗期间病情反复的原因。方法 将上海交通大学医学院附属新华医院2006年1月至2010年12月期间收治的102例变应性哮喘合并鼻炎的患儿,分为治疗组和对照组,治疗组78例在哮喘规范化防治基础上联合粉尘螨注射液特异性免疫治疗,而对照组24例以吸入激素等规范化防治为主。评价两组患儿治疗6个月、1年、2年及治疗结束后随访1年哮喘最大呼气流量(PEF)、汉化版儿童哮喘控制测试量表(Ch-CACT)结果和变应性鼻炎的临床症状评分及视觉模拟评分(VAS),比较两组患儿治疗第2年及治疗结束后随访1年哮喘急性发作次数和呼吸道感染情况,并分析特异性免疫治疗期间病情反复的原因。结果 治疗第2年及治疗结束后随访1年哮喘急性发作次数和呼吸道感染次数均较对照组减少,差异具有统计学意义(P<0.01)。治疗组治疗2年及治疗结束后随访1年哮喘PEF测定结果优于对照组,治疗结束后随访1年Ch-CACT较对照组高,差异均具有统计学意义(P<0.05)。治疗6个月、1年、2年及治疗结束后随访1年治疗组变应性鼻炎的临床症状评分和VAS评分优于对照组,差异具有统计学意义(P<0.05)。特异性免疫治疗期间导致病情反复的常见原因为气候因素、呼吸道感染、合并副鼻窦炎及不适当的居室清扫等。结论 特异性免疫治疗能改善哮喘患儿的PEF及Ch-CACT评分,能明显改善变应性鼻炎的临床症状及VAS评分,是一种防治变应性哮喘合并鼻炎持久有效的方法。气候因素、呼吸道感染及合并副鼻窦炎是导致特异性免疫治疗期间病情反复的主要原因。     

Effects of an acaricide on asthmatic children with house dust mite allergy

D'Allergen is a recently available acaricidal and allergen reducing agent. To study any beneficial effects of treating houses with this agent in asthmatic children with dust mite allergy, histamine bronchial responsiveness was measured in 18 children before and 6–8 weeks after their homes were treated with the agent. Comparisons were with nine similar asthmatics whose homes were not treated. The mean provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1s (PC₂₀) increased from 1.02mg/L to 2.07mg/L in all 18 children who were studied (1.01 doubling doses). Bronchial responsiveness was relatively unchanged in a well matched control group of nine children studied over comparable time periods (PC₂₀ pre was 1.25 mg/L, PC₂₀ post was 0.67 mg/L). The results suggest that treating homes with D'Allergen reduces bronchial reactivity in asthmatic residents with house dust mite allergy.     

舌下特异性免疫治疗对尘螨过敏性哮喘儿童的作用

目的：观察舌下特异性免疫治疗(sublingual immunotherapy, SLIT)联合吸入糖皮质激素(inhaled corticosteroids, ICS)与单独ICS治疗尘螨过敏轻、中度哮喘儿童的临床疗效,为哮喘的联合治疗提供更多的选择方案。方法：对尘螨过敏的轻、中度哮喘患儿32例随机分为两组： SLIT组(SLIT联合ICS治疗,18例)和对照组(单独ICS治疗,14例)。两组共30例完成为期1年的临床观察。比较两组患儿ICS给药总量、哮喘日间和夜间症状评分、皮肤点刺试验、肺功能、血清sIgE和sIgG4值、VAS评分（visual analog scale）的差异。结果：SLIT组在1年治疗结束ICS给药总量较对照组显著减少;与对照组相比,SLIT组的日、夜间哮喘症状评分显著降低,肺功能FEF25- 75%值显著增加,sIgE值及VAS评分降低,差异有统计学意义（P<0.05）;皮肤点刺反应计分、FEV1及sIgG4值两组差异无统计学意义（P>0.05）。在整个随访期两组均无严重不良反应。结论：SLIT联合ICS治疗在改善尘螨致敏哮喘患儿的日、夜间哮喘症状、肺功能及VAS评分方面的疗效优于单独使用ICS治疗。［中国当代儿科杂志,2010,12（5）：344-347］     

Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite

While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non-stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non-working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1)) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non-stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.     

影响儿童哮喘尘螨特异性免疫疗效的因素分析

目的：探讨影响尘螨过敏性哮喘患儿特异性免疫治疗（SIT）疗效的因素。方法：监测99例哮喘患儿接受标准化屋尘螨SIT半年（S1期）、1年（S2期）、1年半（S3期）、2年（S4期）以后的哮喘控制水平,分析患儿初诊年龄、哮喘病程、哮喘程度分级、初始血清特异性（sIgE）浓度、是否合并过敏性鼻炎或异位性皮炎、是否合并吸入糖皮质激素治疗及疗程中出现局部和全身副作用情况对哮喘控制水平的影响。 结果：随着SIT疗程的进行,临床控制病例显著增加,未控制病例则明显减少（P<0.01）;患儿初诊年龄在S1和S3期,以及合并过敏性鼻炎或异位皮炎在S1期均显著影响了哮喘的控制水平（均P<0.01）;SIT治疗各期临床控制组的初始血清sIgE浓度均显著高于临床未控制组（均P<0.05）;S1和S2期初始哮喘程度分级较高的患儿较初始哮喘程度分级较低的患儿达到临床控制的比例显著增高（均P<0.05）。结论：SIT的长期疗效可能与疗程长短及总剂量呈正相关;治疗前初始血清sIgE浓度高的患儿较浓度低的患儿可能更早达到临床控制。     

随访方式对哮喘儿童舌下含服粉尘螨滴剂依从性的影响

目的评价不同随访方式对哮喘儿童舌下脱敏治疗依从性的影响。方法将112例哮喘(缓解期)合并鼻炎的儿童在接受脱敏治疗后均选择随访,按自愿方式进行分组:69例接受电话随访者为电话随访组,43例不愿接受电话随访者为医院现场随访组。两组患儿在接受脱敏治疗后均告知脱敏常识,纪录联系电话、起始时间、取药时间和数量,每次取药时随访询问效果并纪录;电话随访组加入电话随访,并及时将疗效、不良反应反馈给专科医师。两组均进行为期1年的观察。结果电话随访组坚持1年治疗59例(85.5%),医院随访组坚持1年治疗16例(37.2%)。两组患儿依从性在第6个月、第9个月和12个月,差异都具有统计学意义(χ2=23.71、25.38、27.93,P均<0.001)。随访过程中,未发现舌下脱敏治疗的严重不良事件。结论电话随访方便、快捷,能有效提高患儿舌下脱敏治疗的依从性。     

粉尘螨滴剂舌下特异性免疫治疗对儿童咳嗽变异性哮喘的有效性

目的：探讨粉尘螨滴剂舌下特异性免疫（SLIT）治疗对儿童咳嗽变异性哮喘的有效性及安全性。方法：将确诊为咳嗽变异性哮喘并且粉尘螨变应原皮肤点刺试验呈阳性反应的106例4～14岁患儿随机分为SLIT组（n=53）和常规治疗组（n=53）。常规治疗组按照儿童哮喘规范化治疗方案治疗,SLIT组在常规规范化治疗的基础上,加用舌下含服粉尘螨滴剂。观察两组患儿治疗后咳嗽哮喘症状评分改善情况及临床症状开始改善的时间,同时检测血嗜酸性粒细胞（EOS）水平以及最大呼气峰流速(PEF)的变化。记录两组不良反应发生情况。结果：治疗25周后,SLIT组的症状评分降低值、PEF升高幅度及血EOS比例下降程度均显著高于常规治疗组,差异均有统计学意义（P＜0.05）;SLIT组症状改善时间较常规治疗组短,差异亦有统计学意义（P＜0.05）。SLIT组的有效率显著高于常规治疗组,差异有统计学意义（85% vs 68%,P＜0.05）。SLIT组部分患儿出现红、肿、瘙痒等局部反应,均于次日自行消失。结论：粉尘螨滴剂舌下免疫对儿童咳嗽变异性哮喘具有良好的效果,且安全性高。     

尘螨过敏性支气管哮喘的舌下免疫治疗研究进展

在尘螨过敏性哮喘的治疗方法中,螨变应原舌下免疫疗法日益受到关注.其机制尚不十分明确,但可以调节Th1/Th2失衡,促进Th1反应.治疗过程中可降低IgE,升高IgG4,抑制过敏反应的发生.口腔黏膜中的朗格汉斯细胞对提高机体耐受性也发挥着一定的作用.近年来越来越多的研究证明舌下免疫疗法具备有效性、安全性及其良好的依从性....     

舌下含服粉尘螨滴剂治疗螨过敏性哮喘患儿的长期疗效

目的 观察舌下特异性免疫治疗(sublingual immunotherapy,SLIT)在治疗期间及停药后1年对过敏性哮喘患儿的疗效.方法 开放、回顾性研究.选择2009年5月至8月在南京医科大学附属南京儿童医院呼吸科就诊的主要对尘螨[粉尘螨和(或)户尘螨]过敏的轻、中度过敏性哮喘患儿80例,年龄4 ～14岁.所有患儿入组时(基线)均已接受抗哮喘药物治疗3个月.分组:(1)SLIT组39例,抗哮喘药物治疗的同时,采用SLIT 2年,停止SLIT后再随访1年,共随访3年;(2)药物组41例,仅采用抗哮喘药物治疗,随访3年.比较SLIT组和药物组在基线,治疗第2年结束时、第3年结束时(停止SLIT 1年时)的哮喘症状评分、用药评分、停药例数、入组前1年、治疗第3年哮喘急性发作频率.结果 (1)症状评分:SLIT 2年结束时,SLIT组患儿哮喘日间症状评分低于药物组(0.18±0.06,0.93±0.12,Z=-4.873,P＜0.05),夜间症状评分差异无统计学意义;停止SLIT 1年时,SLIT组患儿哮喘日间症状评分(0.18±0.06)和夜间症状评分(0.05±0.04)均低于药物组(日间1.46±0.72,夜间0.66±0.14,Z=-5.082,-4.019,P均＜0.05).(2)用药评分和停药例数:SLIT 2年结束时和停止SLIT 1年时,SLIT组用药评分(0.31 ±0.07和0.17±0.06)均低于药物组(0.75±0.12和0.87±0.17,Z=-2.813,-4.106,P均＜0.05);SLIT组停药例数(20例,29例)均多于药物组(10例,13例)(x2 =6.167,14.581,P均＜0.05).(3)入组前1年两组哮喘急性发作频率差异无统计学意义,治疗第3年(停止SLIT 1年)间,SLIT组哮喘急性发作频率小于药物组(0.69±1.20,1.20±1.44,Z=-1.968,P＜0.05).结论 SLIT能明显改善哮喘的症状,减少药物使用和哮喘急性发作,同时在停止SLIT后1年仍能保持疗效.     

哮喘儿童尘螨特异性免疫治疗的全身不良反应

目的了解儿童尘螨特异性免疫治疗(specific immunotherapy,SIT)的全身不良反应。方法对131例尘螨过敏的哮喘患儿进行标准化尘螨提取液特异性免疫治疗,观察每次注射后不良反应发生情况。结果34例(26%)发生全身不良反应,予对症处理后均能缓解,未出现严重不良反应。有全身不良反应的34例与无全身不良反应97例尘螨sIgE比较,差异无统计学意义。全身不良反应的发生主要与注射变应原的剂量(浓度)有密切关系。结论哮喘患儿对标准化屋尘螨提取液特异性免疫治疗耐受性良好,未发现严重的全身不良反应。