Allergen specific sublingual immunotherapy in children with asthma and allergic rhinitis

Background

The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma.

Data sources

PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search.

Results

Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients.

Conclusions

At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

     

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.     

Vitamin A status in children with asthma

Low vitamin A levels have been found in a number of diseases in children. The aim of this study was to examine the vitamin A status in children with asthma and to correlate the changes with severity of disease. Serum levels of vitamin A, retinol‐binding protein (RBP), and albumin were estimated in 35 asthmatic children (24 males) in the age group of 2–12 years (mean 5.89 years) and 29 controls (19 males). Both study and control groups were similar with respect to age, sex, and overall nutritional status. Twenty‐four children in the study group (68.6%) had moderate to severe persistent asthma and eight children had mild persistent asthma. Only three patients suffered from mild intermittent asthma. Vitamin A levels in children with asthma (mean ± SD 22.14 ± 5.38 µg/dl) were found to be significantly lower than their controls (mean ± SD 27.54 ± 4.83 µg/dl) (p = 0.0001). Age, age of onset of asthma, and gender had no correlation with serum vitamin A levels. Low serum vitamin A levels (< 20 µg/dl) were observed four times more commonly in the study group (28.6%) than controls (6.9%). Severity of asthma had a negative correlation with serum vitamin A levels (r = ? 0.61, p = 0.0001). Children with severe persistent asthma had markedly low serum vitamin A levels (mean ± SD 13.42 ± 5.19 µg/dl) as compared with mild intermittent asthma (mean ± SD 24.61 ± 2.32 µg/dl). Therapeutic trials are needed to prove whether low vitamin A levels contribute to asthma severity and the clinical utility of vitamin A supplementation in asthmatic children.     

Role of BAFF in pediatric patients with allergic rhinitis during sublingual immunotherapy

Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than treating symptoms simply. However, its regulatory mechanisms are largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very important roles in the development, differentiation, and proliferation of B cells and T cells. The aim of this study was to identify the role of BAFF during SLIT in pediatric patients with AR. Seventy-two house dust mite (HDM)-sensitized pediatric patients with AR were enrolled in this study. Thirty-six pediatric patients received HDM allergen extract for SLIT and 36 pediatric patients received placebo. Serum and nasal aspirate of different time points during treatment was collected and used for enzyme-linked immunosorbent assay (ELISA) of BAFF and related cytokines, respectively. Peripheral blood mononuclear cells were collected and stimulated by HDM allergen with or without rhBAFF after 12 months of treatment. Our results showed that the expression of BAFF protein decreased during the SLIT treatment compared with that in the placebo group after 6 months of therapy, and this trend lasted for 12 months. The decreased BAFF expression was positively related to Th2 cytokines and increased IL-10 expression. BAFF was also related to local production of IgA. In vitro experiments showed that BAFF can promote Th2 cytokines and inhibit IL-10 expression by PBMCs. Conclusion: During SLIT, BAFF expression was decreased and related to low Th2 cytokine expression and enhanced IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our results suggested that BAFF may be an important biomarker during SLIT. Authors’ summary. Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than simply treating symptoms. However, its regulatory mechanisms are largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very important roles in the development, differentiation, and proliferation of B cells and T cells. Our results showed that during SLIT, BAFF expression was decreased and related to low Th2 cytokine expression and enhanced IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our results suggested that BAFF may be an important biomarker during SLIT.     

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。     

New visions in specific immunotherapy in children: an iPAC summary and future trends

Specific immunotherapy is indicated for confirmed immunoglobulin E-mediated airway diseases using standardized allergen products with documented clinical efficacy and safety. For decades the subcutaneous route of administration (SCIT) has been the gold standard. Recently, the sublingual immunotherapy (SLIT) has also been investigated in children. SCIT, especially with grass and birch pollens but also house dust mites, is an effective treatment in children with allergic rhinitis and asthma when a significant part of their symptoms are caused by these allergens. A long-term effect up to 12 yr after discontinuation of SCIT with timothy allergen has been shown. Efficacy and safety of SLIT in pollen allergic rhinoconjunctivitis have been demonstrated in adults. The evidence in children is a little less convincing, and more data is needed. The clinical relevance, long-term results and the size of the effect, as well as the dose, the treatment regimen and duration has not been sufficiently elaborated. It is demonstrated that SCIT has the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. Also one randomized study indicates a preventive effect of SLIT in children on the development of asthma. At present, there are no studies who clearly demonstrates either a long-term effect or a preventive effect on the development of asthma of SLIT in children. The areas with lack of evidence should be addressed in well performed prospective, randomized long-term studies both with SCIT and SLIT. This review was initiated by iPAC (international Pediatric Allergy and Asthma Consortium) and aims to review current knowledge related to specific immunotherapy in childhood, and to identify needs for future research in this field.     

Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy

Mösges R, Graute V, Christ H, Sieber H‐Jochen, Wahn U, Niggemann B. Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy.
Pediatr Allergy Immunol 2010: 21: 1135–1138.
© 2010 John Wiley & Sons A/S The recommendation to use sublingual‐swallow immunotherapy (SLIT) in children and adults with allergic rhinitis has been established over the past decade. Recently, ultra‐rush titration of SLIT has become more and more common, raising concerns about its safety in children with asthma. Fifty‐four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen (birch and possibly alder and/or hazel) from 14 study centers in Germany participated in a randomized, double‐blind, and placebo‐controlled study. Twenty‐seven were randomized to receive SLIT with standardized birch pollen allergen extract and the other 27 to receive placebo. An ultra‐rush high‐dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity (IR) within 90 min (30–90–150–300 IR) was used. The difference in mean PFR changes during ultra‐rush titration between SLIT and placebo was not significant (p = 0.056). A 95% probability that SLIT does not decrease PFR during ultra‐rush titration was demonstrated. Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred. No serious adverse event assessed by the investigator as related to study drug treatment was reported.     

舌下特异性免疫治疗过敏性鼻炎/过敏性哮喘患儿IL-17和IL-35水平的变化及临床疗效

目的 探讨舌下特异性免疫治疗(SLIT)的机制,并评价SLIT的临床疗效.方法 随机选取2011年1~12月行SLIT治疗的粉尘螨过敏性鼻炎(AR)和/或过敏性哮喘(AS)患儿30例为病例组,另随机选取行体检的30例健康儿童为对照组.检测病例组行SLIT治疗前及治疗1、2年时的1秒钟用力呼气容积(FEV1)或气道阻力与预计值之比、嗜酸性粒细胞(Eos)计数及血清细胞因子IL-17和IL-35水平,与对照组进行比较分析;同时对病例组患儿的鼻炎/哮喘症状进行评分并监测哮喘控制水平.结果 病例组SLIT治疗前、治疗1年时IL-17水平均明显高于对照组(P<0.01);且IL-17水平在治疗前、治疗后1年及治疗后2年呈逐年下降趋势(P<0.01),至治疗2年时与对照组比较差异无统计学意义(P>0.05).血清IL-35水平在治疗前后的变化趋势与IL-17的变化趋势刚好相反.FEV1与预计值之比在治疗前、治疗后1年及治疗后2年呈逐年上升趋势(P<0.01);而气道阻力与预计值之比、Eos计数则呈逐年下降趋势(P<0.01).病例组SLIT治疗2年时的鼻炎症状总评分和哮喘症状总评分改善百分率均较治疗1年时明显增高(P<0.01);SLIT治疗AR 1年时显效率85%,2年时达100%;SLIT治疗AS 1年时控制率为76%,2年时控制率达92%.结论 SLIT是一种有效治疗儿童AR和AS的方法,可能是通过抑制IL-17并促进IL-35的表达水平从而达到治疗目的,且治疗2年的效果较1年更好.     

Asthma and atopy in schoolchildren in a defined population

We investigated the frequency of allergic disorders, the pattern of allergen sensitization and serum total IgE concentration in a population-based sample of schoolchildren screened on the basis of respiratory symptoms ( A = 244). The children were classified on clinical grounds into three groups, asthma ( N = 43), other symptoms from lower airways (OSLA; N = 34) and control children ( N = 167). The frequency of allergic disorders (allergic rhinitis, conjunctivitis or dermatitis) differed significantly between children with asthma (81%), children with OSLA (62%) and in control children (48%) ( p < 0.001). The presence of at least one positive skin prick test result was equally common in children with asthma or OSLA (77%), but lower in control children (40%) ( p < 0.001). Serum total IgE concentrations did not differ between the three groups. Two conclusions can be drawn: (i) there is a strong association between clinical allergy, skin reactivity and asthma in school age children, and (ii) a similar association is present between allergy and asthma-like conditions.     

Aeroallergen sensitisation patterns of children aged 5 years and younger with asthma and/or allergic rhinitis in Istanbul

Aim of the studyThe purpose of the study was to determine the aeroallergen sensitisation patterns of children aged 5 years and younger with asthma (AS) and/or allergic rhinitis (AR) in Istanbul, Turkey.MethodsThis cross-sectional observational study was conducted between January and December 2018 in the outpatient clinic of a hospital department of pediatric allergy. Patients, who had regular outpatient controls, full clinical and laboratory records, positive skin prick test results, and were willing to participate in the study, were included.ResultsIn total, 148 children aged 5 years or younger who had positive skin prick test results were included in the study. The male/female ratio and the mean age at onset of symptoms were 87/61 and 2.13 ± 1.33 (0.4–4.5) years, respectively. Of the 148 patients, 63 (42.6%) had AS, 11 (7.4%) AR, and 74 (50.0%) had both AS and AR. The age of the patients, age at symptom onset, male/female ratio, number of allergen sensitivities, total IgE levels, total eosinophil levels, and skin prick test results for aeroallergens did not differ between the patients with AS, AR, and AS + AR. House dust mite (HDM) was the most common aeroallergen in patients, while the cockroach was the least common aeroallergen. The severity of asthma and control levels were not found to be associated with aeroallergen sensitisation in children.ConclusionOne out of every four atopic children aged 5 years or younger is sensitised to aeroallergens. The most common sensitisation is to house dust mites. Weed aeroallergen may be related to severity of asthma in children aged 5 years or younger in Istanbul. We speculate that HDM and weed allergens could be used in the diagnostic or treatment strategies for the management of asthmatic children aged 5 years or younger.     

Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children (EASY Project: Evaluation of A novel SLIT formulation during a Year)

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self-managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real-life setting. A simplified schedule of SLIT was used, consisting of a 10-day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2-13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real-life confirm that the compliance with SLITOne is good, despite the therapy managed at home.     

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.     

Sublingual Immunotherapy Decreases Expression of Interleukin-33 in Children with Allergic Rhinitis

Objectives

To identify the expression of IL-33 during SLIT (Sublingual immunotherapy) in AR (Allergic rhinitis) children.

Methods

Thirty children received house dust mite (HDM) allergen extract for SLIT and thirty children received placebo in this study. Serum and nasal lavage samples of cases and controls were collected at different time points during SLIT. Interleukin (IL)-33 and other cytokines were estimated in these samples by enzyme-linked immuno sorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were prepared and stimulated with rhIL-33 (with or without other stimulators) at different time points during SLIT.

Results

The present results showed that both serum and nasal lavage of IL-33 levels decreased significantly after 12 mo treatment and this trend maintained at least until 24 mo. The decreased nasal IL-33 level was positively correlated to local Th2 cytokines and increased IL-10 expression at 2 y post SLIT treatment. In vitro experiments showed that IL-33 promotes IL-4 and IL-5 and inhibits IL-10 expression by peripheral blood mononuclear cells (PBMCs) in AR.

Conclusions

Decreased IL-33 expression during SLIT may contribute to low Th2 response and enhanced Regulatory T cell cytokines expression. Thus, IL-33 maybe an important predictor during SLIT.

     

Analysis of the inhalant allergen spectrum in 4488 children with allergic rhinitis in Tianjin北大核心CSCD

目的探讨天津地区儿童过敏性鼻炎(AR)吸入性变应原种类及特点,为儿童AR预防与诊疗提供依据。方法回顾性收集2016年3月至2022年2月天津医科大学第二医院儿科哮喘和过敏专病门诊AR患儿4488例的临床资料,分析儿童AR的吸入性变应原分布特点,探讨吸入性变应原阳性率及变应原种类与性别、年龄以及共患其他过敏性疾病的关系。采用UniCAP100系统(荧光酶联免疫法)测定血清变应原特异性IgE(sIgE)。计数资料以例数及百分率(%)表示,组间比较采用χ^(2)检验。结果1.4488例AR患儿中吸入性变应原阳性3116例,阳性率69.43%。单一变应原阳性比例28.47%(887/3116)、双重变应原阳性比例25.22%(786/3116)、3种变应原阳性比例19.67%(613/3116)、4种及4种以上变应原阳性比例26.64%(830/3116)。最常见吸入性变应原为霉菌类(45.72%,2052/4488),其次依次为粉尘螨(34.71%,1558/4488)、艾蒿(33.95%,313/922)、屋尘螨(31.13%,1397/4488)、豚草(30.97%,227/733)等。2.学龄前组、学龄组、青少年组吸入性变应原阳性率依次为56.15%(1132/2016)、79.26%(1624/2049)、85.11%(360/423)(χ^(2)=309.72,P<0.001)。在学龄前组、学龄组首位吸入性变应原均为霉菌类(40.23%、50.85%),在青少年组首位吸入性变应原为粉尘螨(56.74%),其次为屋尘螨(53.66%)、霉菌类(47.04%)。3组吸入性变应原阳性种类比较差异有统计学意义(χ^(2)=466.99,P<0.001)。在学龄前期组以单一变应原阳性为主,学龄组、青少年组吸入性变应原阳性种类增多,以4种及4种以上变应原为主。3.男童组吸入性变应原阳性率达73.28%(2139/2919),明显高于女童组阳性检出率62.40%(979/1569)(χ^(2)=58.28,P<0.001),男童和女童组常见吸入性变应原前3位均为霉菌类、艾蒿、粉尘螨。吸入性变应原阳性种类在男童与女童组比较差异有统计学意义(χ^(2)=75.02,P<0.001),女童组以单一变应原为主(20.78%),男童组变应原阳性种类增多,以4种及4种以上变应原阳性为主(20.45%)。4.AR共患支气管哮喘和特应性皮炎组吸入性变应原阳性率最高,达79.21%,其次AR共患支气管哮喘阳性率73.67%,AR共患特应性皮炎组阳性率61.05%,单纯AR组阳性率57.05%,组间比较差异有统计学意义(χ^(2)=178.57,P<0.001)。结论天津地区儿童AR主要吸入性变应原依次为霉菌类、粉尘螨、艾蒿、屋尘螨、豚草,不同年龄、性别及共患不同过敏性疾病吸入性变应原分布特征存在差异。应尽早为AR患儿检测变应原,做到提前预防,减少药物使用量,也为开展变应原免疫治疗提供依据。     

Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

Halken S, Agertoft L, Seidenberg J, Bauer C‐P, Payot F, Martin‐Muñoz MF, Bartkowiak‐Emeryk M, Vereda A, Jean‐Alphonse S, Melac M, Le Gall M, Wahn U. Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.
Pediatr Allergy Immunol 2010: 21: 970–976.
© 2010 John Wiley & Sons A/S The efficacy and safety of five‐grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5–11 yr) and adolescents (12–17 yr) with grass pollen–allergic rhinoconjunctivitis were included in a multinational, randomized, double‐blind, placebo‐controlled study and received either a 300IR five‐grass pollen tablet or placebo daily in a pre‐ (4 months) and co‐seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five‐grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.     

Metabolic syndrome in obese children born large for gestational age

Objective This study was to compare the prevalence of metabolic syndrome (MS) and insulin release in Chinese obese children born large-for-gestational age (LGA) with those born appropriate-for-gestational age (AGA). Methods Obese children were divided into LGA group (n = 60) and AGA group (n = 312); clinical and metabolic characteristics were collected. An oral glucose tolerance test was performed to detect glucose and insulin concentration at 0, 30, 60, 90, and 120 min. Differences between parameters were compared in the two groups and MS was determined. Results The age of adiposity rebound (AR) was earlier and the period from AR to hospitalization was longer in LGA group than AGA group (4.58 ± 3.35 years vs 5.64 ± 3.08 yr, p=0.016 and 5.87 ± 2.85 yr, vs 4.98 ± 2.7 yr, p=0.02). There were no differences in β-cell function, insulin resistance, insulin sensitivity and Disposition index between the two groups. Fasting insulin (FINS) and area under curve of insulin (AUCI) showed differences between two groups. The prevalence of MS was 65% for LGA group, which was significantly higher than AGA group (42.3%). LGA status increased the risk of MS with hazard ratios of 2.53 [95% confidence intervals (CI): 1.42–4.51]. Timing of AR showed significant negative correlation with hypertriglyceridemia (r = −0.497, P = 0.01). Multiple logistic regression analysis identified age at AR as an independent factor associated with blood triglyceride level. The prevalence of hypertension and hypertriglyceridemia was independently associated with LGA [adjusted odds ratios (95% CI) 2.41 (1.39–4.36), P = 0.003; 2.18(1.21–3.72), P = 0.016]. Conclusions There was a younger trend in age of AR in obese children born LGA. The prevalence of MS was particularly higher in obese pediatric populations born LGA. Hypertension and hypertriglyceridemia were better components for diagnosis of MS in obese children.     

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］     

大鼠发育早期接触变应原对Th1/Th2亚群功能及哮喘发生的影响

目的 探讨妊娠期母鼠及其子代接触尘螨点刺液（Der p）对发育后期个体Th1/Th2平衡及哮喘发生的影响。方法 Wistar大鼠根据母体妊娠期及新生早期是否接触Der p随机分为对照组、母Der p-仔Der p-组（母鼠和其子代均未接触Der p）、母Der p+仔Der p+组（母鼠和其子代均接触Der p）和母Der p+仔Der p-组（母鼠接触Der p,其子代未接触Der p）,分别皮下注射Der p或生理盐水,30 d龄时除对照组外,其余3组以卵白蛋白（OVA）为变应原致敏并雾化吸入,诱发哮喘发生。取血浆检测OVA特异性IgE抗体、收集外周血单个核细胞（PBMC）用ELISA法检测培养上清中细胞因子IL-4和IFN-γ水平,行支气管肺泡灌洗记录支气管肺泡灌洗液（BALF）中嗜酸性粒细胞的计数,留取肺组织行病理学检查。结果 母Der p+仔Der p+组在哮喘建模后PBMC培养上清中IFN γ水平显著低于母Der p-仔Der p-组,IL-4水平显著升高,IL-4/IFN-γ比值升高,OVA特异性IgE、BALF中嗜酸性粒细胞计数显著高于母Der p-仔Der p-组;母Der p+仔Der p-组与母Der p-仔Der p-组IL-4和IFN-γ水平差异均无统计学意义,OVA特异性IgE水平虽有增高,但差异不具统计学意义,BALF中嗜酸性粒细胞计数差异无统计学意义。母Der p+仔Der p+组Th2优势显著高于母Der p+仔Der p-组。 结论 胎鼠对于Der p跨胎盘的致敏作用可通过母体妊娠期间的免疫来完成,这一过程会根本上导致Th2优势免疫的发生,增加了变态反应性疾病的危险性。     

Hospital admission with neonatal sepsis and development of atopic disease: Is there a link?

The role of suspected or confirmed neonatal sepsis in modifying the risk of atopic disease during childhood was assessed. Children with early-onset neonatal sepsis were identified from a cohort of neonates, hospitalized between 1990 and 1995. Of 196 individuals, 140 were recruited (71.4%). Pre- and postnatal history was ascertained from neonatal medical records. Based on clinical symptoms and a positive blood culture or at least three of initially defined laboratory or bacteriological criteria, they were stratified in either confirmed neonatal sepsis (CS) or suspected sepsis (SS) group. A control group (C) comprised children who were never hospitalized during infancy (n = 696). Primary end-point was the development of atopic dermatitis, bronchial asthma or allergic rhinitis during childhood (mean age 8.4 yr, range 5.7-12.4). CS and SS children had a higher prevalence of atopic dermatitis (CS 15.7%, SS 21.4%) compared with controls (C 5.2%, p < 0.001). Similarly, children with SS (7.1%), but not with CS (4.3%) had significantly more often a doctor's diagnosis of bronchial asthma compared to controls (1.9%, p = 0.02). No difference in the prevalence of allergic rhinitis was observed (CS 4.3%, SS 10%, C 8.3%). After adjusting for parental history of atopic disease and demographic factors, no significant difference for the risk to develop atopic dermatitis, asthma or allergic rhinitis among the groups was calculated in children with normal birth weight (>2500 g). Our data failed to show a possible link between hospital admission with SS and development of atopic disease.