Efficacy of specific immunotherapy in children with seasonal allergic rhinitis and conjunctivitis,sensitized to grass pollen

The aim of this study was the evaluation of efficacy of the specific immunotherapy using Pollinex for 3 years before the period of pollen dust in children with seasonal allergic rhinitis and conjunctivitis induced by grass pollen. The study was carried out in a group of 40 children aged 5-18 years, from the Outpatient Department of Immunology at the National Research Institute of Mother and Child. The children demonstrated clinical symptoms of seasonal allergic rhinitis with conjunctivitis and had a medical history typical for this disease. Diagnostic procedures including skin prick tests and estimation of specific IgE to grass pollen by Pharmacia - CAP system, gave positive results. The efficacy of therapy was monitored by a clinical score with 4-0 points, recording symptoms relating to intensity of rhinoedema, rhinorrhea, sneezing, itching, oedema, conjunctival congestion, pain and lacrimation. In the study group, 39 children (97%) with seasonal rhinitis and conjunctivitis treated by specific immunotherapy (Pollinex) improved. This was confirmed by a statistically significant difference. The results indicate that the specific immunotherapy is an effective treatment of seasonal allergic rhinitis with conjunctivitis in children sensitized to grass pollen.     

Bet v 1-specific IgA increases during the pollen season but not after a single allergen challenge in children with birch pollen-induced intermittent allergic rhinitis

Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been found in the nasal fluid of patients with allergic rhinitis. IgA may play a protective role, but there are also data which show that allergen-specific IgA can induce eosinophil degranulation. The aim of this study was to quantitate Bet v 1-specific IgA in relation to total IgA in the nasal fluid of children with birch pollen-induced intermittent allergic rhinitis and healthy controls, after allergen challenge and during the natural pollen season. Eosinophil cationic protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 healthy controls. Samples were taken before the pollen season, after challenge with birch pollen and during the pollen season, before and after treatment with nasal steroids. During the pollen season, but not after nasal allergen challenge, Bet v 1-specific IgA increased in relation to total IgA in children with allergic rhinitis. No change was found in the healthy controls. The ratio of Bet v 1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in the allergic children, p < 0.001. No change was seen after treatment with nasal steroids, although symptoms, ECP and eosinophils were reduced. In conclusion, allergen-specific IgA in relation to total IgA increases in nasal fluids during the pollen season in allergic children but not in healthy controls. These findings are compatible with the hypothesis that allergen-specific IgA plays a role in the allergic inflammation and further studies are needed to clarify the functional role of these allergen-specific antibodies.     

Omalizumab (Xolair) in children with seasonal allergic rhinitis: Leukotriene release as a potential in vitro parameter to monitor therapeutic effects

To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy.     

Efficacy of pollen immunotherapy in seasonal allergic rhinitis

BACKGROUND: The efficacy of subcutaneous pollen immunotherapy has been documented in published double-blind, placebo-controlled studies related to treatment of seasonal allergic rhinitis. In the present study, subjective (symptom scores) and objective (nasal peak inspiratory flow, nasal smear, nasal biopsy) parameters were used to study the efficacy of pollen immunotherapy. METHODS: Forty-eight patients (32 male), mean +/- SE age 13.6 +/- 2.8 years allergic to grass-pollen participated in the present study. Patients were divided into three groups: group I, 24 patients who did not receive pollen immunotherapy; group II, 12 patients who received the build-up phase of pollen immunotherapy; and group III, 12 patients who had just finished pollen immunotherapy. With regard to objective and subjective parameters these three groups were compared. RESULTS: When group I was compared to groups II and III, the patients who had not received any immunotherapy were found to have a high daytime nasal symptoms score (P < 0.01), high daytime eye symptoms score(P < 0.01) and high night-time symptoms score (P < 0.01). In objective parameters, it was found that group I had low nasal peak inspiratory flow (P < 0.05), and a high eosinophil count in nasal smears (P < 0.05) and peripheral blood (P < 0.05). It was also demonstrated that there was an increased eosinophil infiltration (P < 0.01) and mast cell infiltration (P < 0.05) in nasal biopsy in group I. There was no significant difference between group II and group III according to these results (P > 0.05). CONCLUSIONS: Immunotherapy leads to a better clinical and histopathological prognosis in children with seasonal allergic rhinitis.     

Do the leukotriene receptor antagonists work in children with grass pollen‐induced allergic rhinitis?

Although cysteinyl-leukotriene receptor antagonists were recently approved for use in allergic rhinitis (AR), there has been no study to date investigating their application in children. The aim was to evaluate whether montelukast provides any benefit in nasal allergen challenge-induced symptoms in children, and whether it could improve the control provided by an antihistamine during pollen season. Two randomized studies, one a double-blind, placebo-controlled, nasal allergen challenge study and one an open-label, cross-over, parallel-group clinical study, were performed in 18 (11.7+/-0.7 years) and 32 children (10.5+/-0.5 years), respectively, with grass pollen allergy. In the first study, the effect of a single dose of montelukast and its combination with loratadine were compared with placebo on nasal responses induced by allergen challenge. In the second study, the additive effect of montelukast to loratadine was tested in an open-label cross-over clinical study. In the challenge study, early-phase and late-phase nasal reactions peaked at 15 min and 4 h after the challenge respectively. During the early phase, combination improved total nasal symptoms (p=0.004) during the first hour and sneezing (p=0.012) at 15 min compared with placebo group. During the late phase, montelukast (p=0.017) and combination (p=0.011) caused less nasal obstruction at 4 h and combination caused less sneezing at 6 h (p=0.015). In the clinical trial, montelukast provided protection on seasonal increase in pulmonary symptoms [0 (0, 14) vs. 6.5 (0, 27.7); p=0.016] and on the decrease in FEF25-75 [-0.09 (-0.34, 0.17) vs. -0.28 (-0.66, 0.02); p=0.002]. However, there was no improvement in nasal symptoms and flows. Although we showed protection against nasal challenge-induced congestion with montelukast, we were not able to show the same in the clinical study possibly because of low pollen counts and mildness of the symptoms of the patients with AR. However, montelukast provided better control of pulmonary symptoms and protection from seasonal decrease in lung function, indicating its potential therapeutic benefit in children with AR.     

Urinary leukotriene E4 levels in children with allergic rhinitis treated with specific immunotherapy and anti-IgE (Omalizumab)

Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy. The aim of this study was to investigate the effect of anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene E₄ (LTE₄) levels. Children and adolescents with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomized to receive SIT for either birch or grass pollen and to receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen season. From a total population of 225 children, we collected three urine samples in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2–17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9): SIT (grass or birch) + placebo]. Urine samples were collected before, during and at the end of treatment. Endogenous urinary LTE₄ was separated by high-performance liquid chromatography (HPLC) and determined by enzyme immunoassay with a specific antibody. No differences in urinary LTE₄ concentrations were observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE₄ levels are not helpful in monitoring patients treated with anti-IgE and SIT.     

Clinical and immunological response to oral and subcutaneous immunotherapy with grass pollen extracts

Forty children allergic to grass pollen were divided into two groups, and matched by their serum IgE antibody concentrations to grasses. For two preseasonal treatment periods one group received immunotherapy with an alum adsorbed grass pollen extract, while the second group was treated orally with an aqueous extract of the same allergens.The patients' postseasonal self evaluation as well as the mean symptom scores calculated from symptom diaries indicate, that oral treatment is significantly less effective in controlling seasonal allergic symptoms than subcutaneous immunotherapy. During oral treatment neither an increase of specific serum IgG antibodies, nor a suppression of the seasonal increase in specific serum IgE antibodies could be demonstrated.     

Local allergic rhinitis: A critical reappraisal from a paediatric perspective

The so‐called local allergic rhinitis (LAR) has been proposed as a phenotype of rhinitis with Th2‐driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of ‘systemic’ atopy (negative skin prick test and serum allergen‐specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this ‘Rostrum’ was to critically discuss data and implications of the ‘LAR concept’ in paediatrics. In the natural history of rhinitis due to IgE‐mediated reactions triggered by exposure to allergens, a ‘LAR’ can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to ‘systemic’ IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term ‘local allergic rhinitis’ may be inappropriate, as rhinitis is always ‘local’, while IgE sensitization can be either ‘local’ or ‘systemic’.     

The influence of exposure to house dust mite, cat, pollen and fungal allergens in the home on primary sensitisation in asthma

The homes of 68 atopic asthmatic children were studied to estimate the concentrations of perennial and seasonal aeroallergens (Der pl, Fel d1, grass pollen, tree pollen, Cladosporium , Aspergillaceae and Alternaria ) to which children were likely to have been exposed during their first few months of life, by sampling in the child's month of birth. There was a strong association between the presence or absence of the house dust mite allergen Der p1 in the air with the skin test and IgE antibody test results (p < 0.001), with a similar association for cat allergen Pel d 1 (p < 0.01), when using a low volume sampler (equivalent to the minute tidal volume of a small baby). No significant correlation was found between levels of allergen in carpet dust and air in the same room. There was a strong indication that the presence of a cat at birth was linked with a higher risk of development of allergy to cat, but high levels of Fel d 1 were sometimes found in homes even when there was no cat present, indicating that allergen may be introduced from other sources. The levels of tree pollen were significantly higher in the homes of tree pollen-allergic children than in the homes of patients without this sensitivity (p < 0.01); and the degree of sensitivity, determined by RAST, correlated significantly to the level of tree pollen in the home (p < 0.001). However, no relationship was found between specific sensitivity and the levels of Cladosporium , Aspergillaceae, Alternaria or grass pollen measured in the homes. The effect of high allergen exposure was most prominent in children under 7 yr and not beyond that age.     

Natural exposure to Alternaria spores induces allergic rhinitis symptoms in sensitized children

Allergic rhinitis is associated with exposure to inhaled allergens. Allergic sensitization to the fungus Alternaria is common, especially in warm climates, but the relevance of sensitization to Alternaria in the generation of rhinitis has not been elucidated. The aim of this study was to determine whether natural exposure to Alternaria induces rhinoconjuctivitis symptoms in Alternaria-sensitized children. Symptoms of rhinoconjuctivitis in 132 atopic (measured by skin prick tests) children (aged 7–12 years) in inland New South Wales Australia were measured using parent-completed questionnaires in summer and winter 1998. Airborne concentrations of Alternaria spores and grass pollen were measured throughout the study period using a Burkard volumetric trap. The relation between airborne concentrations of Alternaria spores and symptoms of rhinoconjunctivitis was examined using Wilcoxon's matched pairs signed ranked test and generalized estimating equations. The proportion of children atopic to Alternaria reporting symptoms of rhinitis was significantly higher in the summer, when airborne concentrations of Alternaria were high, than in the winter, when airborne concentrations were low (66.2% vs. 38.2% for nasal symptoms at night, p = 0.0001, 70.6% vs. 51.52% for nasal symptoms during the day, p = 0.02). The proportion of children using anti-allergic treatment was also higher in summer than in winter (anti-allergic medication for the nose 39.7% vs. 17.7%, p = 0.0003). A strong correlation between airborne concentrations of grass pollen and Alternaria was found (R = 0.94, p < 0.001). However, when all children atopic to ryegrass were excluded from the analyses, significant associations between symptoms and season remained. We conclude that exposure to Alternaria spores may be an important cause of allergic rhinoconjunctivitis.     

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.     

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.     

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.

     

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目的比较3~14岁哮喘和变应性鼻炎患儿吸入性致敏原分布特征的异同。方法2004-10—2005-10,北京儿童医院对527例哮喘和620例变应性鼻炎患儿进行吸入性致敏原皮肤点刺试验(skin prick test,SPT),分析比较检出阳性的致敏原在两组病例中的分布特征。结果哮喘和变应性鼻炎患儿SPT阳性检出率分别为77·8%和78·9%(χ2=0·823,P>0·05)。户尘螨、粉尘螨、交链孢霉、猫上皮、艾蒿是两种疾病主要致敏原。哮喘患儿户尘螨、粉尘螨、混合霉菌的阳性率分别为64·6%、59·8%、8·8%,均高于变应性鼻炎患儿(49·5%、47·9%、3·9%,均P<0·05)。变应性鼻炎患儿杂草花粉和艾蒿的阳性率分别为25·6%、26·0%,均高于哮喘患儿(19·3%、19·3%,均P<0·05)。40·2%的哮喘和46·2%的变应性鼻炎为单致敏原阳性。尘螨霉菌混合致敏及尘螨宠物混合致敏在哮喘和变应性鼻炎中最为常见。结论尘螨、霉菌、夏秋季花粉和宠物是3~14岁哮喘和变应性鼻炎患儿主要吸入性致敏原,两病具有相似的致敏原分布特征,但尘螨及霉菌过敏多见于哮喘,夏秋季花粉过敏多见于变应性鼻炎。     

Allergic rhinitis in children

Allergic rhinitis affects up to 40% of children but is commonly undiagnosed. Careful assessment of nasal symptoms allows for the most appropriate therapeutic options to be chosen. Allergen avoidance is often difficult in practice. Antihistamines are of limited benefit in allergic rhinitis caused by house dust mite and other perennial allergens, where symptoms, predominantly nasal obstruction, are not histamine mediated. In contrast, symptoms triggered by pollen, such as nasal itch, rhinorrhoea and sneezing, are relieved by antihistamines. Intranasal steroids are the treatment of choice for persistent moderate–severe allergic rhinitis and are more effective than antihistamines for relief of nasal obstruction. Failure to respond to intranasal medications is often caused by poor compliance or inefficient use of nasal sprays. Immunotherapy may be a useful, if expensive, option, particularly where symptoms are because of a specific pollen. The benefits of immunotherapy in house dust mite‐induced rhinitis and asthma remain controversial.     

Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitis

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and α₂-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of α₂-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in α₂-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.     

长期特异性免疫治疗对螨过敏儿童血清IgG4的影响

目的探讨长期特异性免疫治疗对螨过敏儿童血清IgG4的影响。方法对60例过敏性哮喘和(或)过敏性鼻炎的患儿,予屋尘螨特异性过敏原免疫治疗,在治疗前、治疗16周、治疗1年和治疗3年时分别进行血清IgG4检测。结果随着治疗的进行,螨特异性IgG4显著增高(F=83.91,P<0.001),各时间段差异均有统计学意义(P均<0.01),并且以治疗剂量递增过程患儿血中螨特异性IgG4含量增长最快,在三年治疗结束时血清IgG4值达到最高。结论螨特异性过敏原免疫治疗对患儿体内免疫状态有明显的调节作用,有利于改善螨过敏患儿的症状和体征。     

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.     

Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.     

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case–control study on 171 patients. The EFESO-children Multicenter Trial

Sublingual‐specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in ‘real life’ in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case–control study to evaluate the effect of SLIT in children (age 6–18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case–control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone^® ALK‐Abellò). Controls (n = 81) were defined as sex‐age‐ and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean ± SD) was 4.5 ± 2.5 in cases and 9.0 ± 3.0 in controls (?50%) (p = 0.0001). MS (mean ± SD) was 2.5 ± 1.9 and 3.6 ± 2.1 in the case and control groups, respectively (?31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2‐yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.