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Allergic rhinitis (AR) is one of the most common chronic diseases in children. However, it remains underdiagnosed and undertreated. Its prevalence has increased in recent years and varies from 2 to 25 %. Symptoms include sneezing, itching, runny nose, and nasal congestion. A correct diagnosis and treatment of AR and its comorbidities such as rhinosinusitis with or without nasal polyposis, conjunctivitis, otitis media, bronchial asthma and respiratory tract infections, are important to reduce the negative impact on the quality of life of the patient and their relatives, and in medical costs. Specific allergen immunotherapy, in correctly selected patients, prevents new sensitizations and reduces bronchial hyperreactivity associated with AR. Taking into account all these reasons, the National Allergy Committee of the Sociedad Argentina de Pediatría proposes current evidence based recommendations., (Sociedad Argentina de Pediatría.)

Asthma and allergic rhinitis (AR) have overlapping clinical and pathologic features, sustained by an underlying T helper 2 bias, resulting in airway inflammation that extends from the nose to the lung. Children who are monosensitized often develop polysensitization over time, and they are at high risk of developing asthma. The effect of allergen immunotherapy (AIT) is allergen specific, resulting in symptom improvement and reduction in medication requirement. It is the only known treatment that alters the natural history of allergic disease and induces long-term remission. A bystander or allergen-nonspecific effect of AIT has also been proposed-that AIT to 1 allergen might reduce the risk of development of sensitization to other allergens. Furthermore, several observational studies and clinical trials, in seasonal (pollen) and perennial (house dust mite) AR, have investigated a protective effect of AIT to prevent asthma. The overall evidence favors an asthma preventive effect of AIT in AR to grass and birch tree pollen. Fewer studies have investigated the use of AIT in children with perennial AR due to house dust mite allergy to prevent asthma, and the results are less convincing. The use of AIT to reduce the risk of progression to asthma, in children with AR, potentially has high impact, and it will make AIT more attractive and cost-effective. However, most studies have been of small sample size or of poor design, using different allergens and AIT methodology, making it challenging to draw firm conclusions. There is a need to do adequately powered studies with optimal design and assess cost-effectiveness of this strategy., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergic rhinitis affects 20% of the population of the UK. It confers a significant health burden upon the individual as it affects the patient's quality of life and is associated with serious comorbidities including asthma, sinusitis and conjunctivitis. Owing to its prevalence, it has a significant economic impact through its effects on education, productivity and use of healthcare resources. This review focuses on the management of allergic rhinitis and potential future treatments, because of the lack of clear national guidelines and because this illness is often misdiagnosed and mismanaged. The article provides a comprehensive overview of allergic rhinitis and illustrates the assessment criteria for various subcategories.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders that induces immunological tolerance through administration of specific allergens. Studies on AIT for subcutaneous route are in abundance; however, the efficacy of AIT in tablet form through sublingual route has not been well elucidated. The present prospective, parallel-group, controlled study sought to compare the efficacy of sublingual immunotherapy (SLIT) tablets with pharmacotherapy (PT) in 332 house dust mite (HDM)-specific allergic asthma and/or rhinitis patients over a period of 3 years. Patients were followed up for a 6-month run-in period and then randomly stratified as those who would receive SLIT, SLIT in addition to PT (SLIT+PT), and PT alone. AIT was administered in the form of sublingual tablets. Symptom and medication scores were measured every 3 months. In vitro evaluation of serum total and HDM specific immunoglobulin E (HDM sIgE) levels was carried out every 3 months, whereas in vivo skin prick test was performed annually for 3 years. Our study demonstrated sustained clinical improvement, reduction in inhaled corticosteroid (ICS) dose and duration as well as prevention from development of neosensitization to other aero allergens in HDM-allergic asthmatics and/or rhinitis patients treated with 3 years SLIT. Despite a remarkable clinical improvement with AIT, we observed that SLIT did not significantly change the skin reactivity to HDM at 3 years and there was no significant change in the ratio of serum total and HDM sIgE. Given the immune and disease modifying effects of AIT in allergic diseases, the present study supports the notion of its sublingual mode being an effective long-term immunomodulator in HDM-sensitized nasobronchial allergies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baba, Rasool, Gull, Qureshi, Beigh, Qadri and Shah.)

Background: The role of salivary-specific IgG4 and IgA in subcutaneous immunotherapy (SCIT) is not well defined. We aimed to investigate the change of IgG4 and IgA in both serum and saliva and their correlations with IgE-blocking-factor (IgE-BF) during SCIT., Method: 307 Dermatophagoides pteronyssinus (DP) allergic rhinitis and/or asthma patients were recruited for this study. 286 patients received DP-SCIT for 1 year. Twenty-one patients received only symptomatic treatment. DP-, Der p 1-, and Der p 2-specific IgE in serum, specific-IgG4 and Der p 2-specific IgA1 and IgA2 in both serum and saliva were measured at timepoints 0, 4, and 12 months during DP-SCIT. Correlation between salivary and serological IgG4, IgA, and their correlation with DP-specific IgE-BF measured in serum was evaluated., Results: During DP-SCIT, the allergen-specific IgG4 in both saliva and serum increased and correlated significantly, the correlation becomes stronger over the treatment time. DP-specific IgE-BF significantly correlated with DP-specific IgG4 in serum (p < 0.0001) at different timepoints and in saliva at 12 months of SCIT (p < 0.01). No change in Der p 2-specific IgA during DP-SCIT was observed, and the IgA in serum did not correlate with IgA in saliva. There was no correlation between DP IgE-BF and Der p 2-specific IgA in serum or saliva. The control group did not exhibit significant changes in any antibody level measured., Conclusion: The IgE blocking activity induced by DP-SCIT treatment correlated with specific IgG4 and not IgA. The IgG4 in saliva correlates with serum IgG4 and can be an alternative immunological marker beyond 1 year of SCIT treatment., (© 2021 S. Karger AG, Basel.)

Allergic rhinitis is the most common chronic disease worldwide. Treatment guidelines have improved the knowledge on rhinitis and have had a significant impact on AR management. In 20 years, ARIA has considerably evolved from the first multi-morbidity guideline in respiratory diseases to the digital transformation of health and care. Allergic rhinitis in Georgia, Next-generation ARIA-GRADE guidelines and ARIA, 2020 care pathways for Allergen Immunotherapy have been discussed in this review.

Introduction: The aim of the study is to indicate the relation between the use of alternative medicine and the occurrence of allergic diseases in the Polish population of adults in the age of 20-44 years. Moreover the additional aim of the study is to define the relation between the sex, age and place of living and the use of alternative medicine., Material and Methods: The data from the project Epidemiology of Allergic Diseases in Poland (ECAP) has been used for analysis. This project was a continuation of the European Community Respiratory Health Survey II. The questions on alternative medicine were asked to the group of 4671 respondents in the age of 20-44 years. Additionally outpatient tests were performed in order to confirm the diagnosis of allergic diseases., Results: The total of 22.2% of respondents that participated in the study have ever used alternative medicine (n = 4621). A statistically significant relation between the use of alternative medicine and declaration of allergic diseases and asthma symptoms has been demonstrated (p < 0.001). No statistically significant relation between the use of alternative medicine by persons diagnosed by a doctor with any form of asthma or seasonal allergic rhinitis (p > 0.05) has been demonstrated., Conclusions: The occurrence of allergic diseases and asthma influences the frequency of alternative medicine use. However the frequency of alternative medicine use does not depend on allergic disease or asthma being confirmed by a doctor.

Allergen Immunotherapy (AIT) is able to restore a physiological Th1 response and Tregs function. This effect is allergen-specific, even though it has been reported that it may also be non-specific, such as also extended to allergens not used in AIT. This immunological phenomenon may also be of clinical nature. This case report shows that a poly-allergic patient, successfully treated with Parietaria extract, also achieved a clinical tolerance towards other causal allergens, such as mites and cat. Of course, this was an anecdote, but it is reasonable to prospect the hypothesis that a bystander clinical effect may be observed during AIT in poly-allergic patients.

The treatment of respiratory allergy is based on several drugs with different mechanisms of action, which encompass an effect only on symptoms, limited factors of inflammation or the whole process of inflammation. Dissecting the different treatments by their mechanism of action is relevant for the management of allergic patients. Corticosteroids, administered as nasal sprays in rhinitis or by inhalation devices in asthma, and allergen immunotherapy (AIT) are the most effective treatments for respiratory allergy, achieving the control on inflammation by a number of cellular and molecular mechanisms. What distinguishes corticosteroids from AIT is the duration of clinical outcomes that ends with treatment withdrawal for the former but persists after stopping for AIT, due to its disease-modifying effect.

Background: Allergen immunotherapy (AIT) is advised for patients with allergic rhinitis who remain symptomatic despite the use of pharmacotherapy and allergen avoidance. Several factors influence the decision to initiate and complete the AIT regimen., Objective: To evaluate patient initiation and persistence with subcutaneous and sublingual immunotherapies (SCIT and SLIT) according to physician recommendation., Methods: A retrospective review of electronic health records of patients with allergic rhinitis for whom AIT was recommended was conducted in a large private allergy practice in Pennsylvania., Results: Of 8,790 patients advised to consider AIT, 36.2% initiated AIT (57% adults, 43% children); 78% chose SCIT and 22% chose SLIT drops. Election of AIT was significantly associated with select comorbidities, specifically chronic sinusitis (8.1% for AIT vs 10% for no AIT), allergic conjunctivitis (12.5% for AIT vs 18.5% for no AIT), and asthma (33.8% for AIT vs 37.4% for no AIT; P < .05). Choice of SCIT vs SLIT drops was significantly associated with older age, female sex, select comorbidities, and more allergy medications at initiation (P < .05). Of adults, 30.2% completed at least 3 years of recommended treatment. Median time on treatment was longer for adults on SCIT vs SLIT drops (3 vs 1.6 years). Similarly, 35.4% of children completed treatment, with a longer median time on treatment for SCIT (4.7 years) vs SLIT drops (3.5 years)., Conclusion: A minority of patients initiated AIT according to allergist recommendation and a subset of these patients completed therapy. AIT might be an underused option that could benefit patients unable to manage allergic rhinitis symptoms by other means., Trial Registration: clinicaltrials.gov Identifier: NCT01549340., (Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives/hypothesis: To systematically review the effectiveness and safety of subcutaneous immunotherapy (SCIT) for treatment of allergic rhinoconjunctivitis and asthma, using formulations currently approved in the United States., Study Design: We searched the following databases up to May 21, 2012: MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials., Methods: We included randomized controlled trials published in English comparing SCIT to placebo, pharmacotherapy, or other SCIT regimens that reported clinical outcomes of interest. Studies of adults or mixed age populations were included. Studies were excluded if the diagnosis of allergy and/or asthma was not confirmed with objective testing. Paired reviewers selected articles for inclusion and extracted data. We assessed the risk of bias for each study and graded the strength of evidence for each outcome as high, moderate, or low., Results: Sixty-one studies met our inclusion criteria. Majority of the studies (66%) evaluated single-allergen immunotherapy regimens. The literature provides high-grade evidence that SCIT reduces asthma symptoms, asthma medication usage, rhinitis/rhinoconjunctivitis symptoms, conjunctivitis symptoms, and rhinitis/rhinoconjunctivitis disease-specific quality of life in comparison to placebo or usual care. There is moderate evidence that SCIT decreases rhinitis/rhinoconjunctivitis medication usage. Respiratory reactions were the most common systemic reaction. There were few reports of anaphylaxis; no deaths were reported., Conclusions: Generally moderate to strong evidence supports the effectiveness of SCIT for treatment of allergic rhinitis and asthma, particularly with single-allergen immunotherapy regimens. Adverse reactions to SCIT are common, but no deaths were reported in the included studies., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both effective treatments for allergic rhinitis and allergic asthma, both show clinical evidence of disease modification by decreasing new sensitizations in individuals who were monosensitized, by reducing the development of asthma in patients with allergic rhinitis, and by inducing clinical improvement that persists for years after discontinuation of a successful course of treatment. Initiation of SLIT is accompanied by a high incidence of local symptoms, but these are generally mild and do not usually persist beyond the first few weeks. Systemic reactions do occasionally occur with SLIT but much less frequently than with SCIT, and, to date, no fatal or near fatal reactions have been reported. Effective doses have been defined for many allergens for SCIT and are now being defined for SLIT. There remains the unanswered question of the effectiveness of SLIT with multiple allergen extracts. The relative clinical efficacy of SCIT and SLIT remains to be defined. When each is compared with placebo, results of meta-analyses suggest greater efficacy of SCIT. In the limited number of randomized, head-to-head studies, SCIT has more often provided greater clinical and immunologic responses. However, head-to-head studies with well-defined effective doses by the 2 routes are urgently needed., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The prevalence of allergic rhinitis (AR) is on the increase and this condition is frequently associated with asthma, thus leading to the concept that these two conditions are different aspects of the same disease. There is now accumulating evidence that AR often precedes the onset of asthmatic symptoms. This notion has important implications, not only for the diagnosis and management of these common allergic conditions but also for the potential progression of disease. Very little is known about the risk factors responsible for the progression of AR to asthma; current treatment options can control symptoms but do not prevent or cure the disease. However, there are recent data supporting the notion that it is possible to prevent new asthma cases by modifying the immune response and clinical outcome with allergen immunotherapy. This review article evaluates the impact of AR on the development of asthma, examines putative predictors for the progression of AR to asthma, and reviews recent, promising literature suggesting that early treatment of allergic individuals with immunotherapy may aid in asthma prevention.

Consideration of the unified airway model when managing patients with rhinitis and or asthma allows a more comprehensive care plan and therefore improved patient outcomes. Asthma is linked to rhinitis both epidemiologically and biologically, and this association is even stronger in individuals with atopy. Rhinitis is not only associated with but is a risk factor for the development of asthma. Management of rhinitis improves asthma control. Early and aggressive treatment of allergic rhinitis may prevent the development of asthma. In patients with allergic rhinitis that is not sufficiently controlled by allergy medication, allergen-directed immunotherapy should be considered., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The prescription of allergen immunotherapy (SIT) in asthma remains a matter of debate and official guidelines often do not provide clear recommendations in this regard., Methods: An extensive review of the literature was untaken., Results: There are many robust studies with SCIT and SLIT showing positive results related to improving asthma symptoms, in particular when asthma was associated with rhinitis. In addition, there are several favourable meta-analyses, although their validity is limited by the heterogeneity of the trials included. The disease modifying effect of SIT (prevention of asthma onset and long-lasting effects) should be considered when prescribing this treatment. Regarding safety, fatalities seem to be rare: in Europe no fatality has been reported over the last two decades, and the same has been observed in USA in the last 4 years. Uncontrolled asthma is universally recognized as the most important risk factor for severe adverse events, but there is no clear demonstration that SIT can worsen or induce asthma. In contrast, of the few studies specifically designed to evaluate asthma, none had a formal sample size calculation, and pulmonary function was assessed as primary outcome only sporadically., Conclusions: According to the presently available evidence, SLIT and SCIT can be used in asthma associated with rhinitis (the most common condition), provided that asthma is adequately controlled by pharmacotherapy. In such cases, a measurable clinical benefit on asthma symptoms can be expected. SIT cannot be presently recommended as single therapy when asthma is the unique manifestation of respiratory allergy.

Background: To date, no predictive methods for the clinical response to allergy immunotherapy (AIT) are available. We sought to evaluate the pretreatment parameters used in diagnosing allergic asthma and/or rhinitis including allergen skin-prick test responses, serum specific and total IgE (sIgE and tIgE) levels and blood eosinophil counts, and to identify whether these can be used to predict clinical effectiveness in children treated with immunotherapy., Methods: This study involved 185 children who had undergone 3 years of standardized-quality house-dust mite subcutaneous immunotherapy. Clinical characteristics and laboratory parameters were analyzed. A multivariate unconditional logistic regression model and receiver operating characteristic curves were used. Predicted probabilities and predictive areas under the curve were calculated., Results: The clinical response to AIT was effective in 129/185 (69.7%) patients. Four variables were associated with clinical response by multivariate logistic analysis: tobacco smoke exposure [odds ratio (OR) 2.845 and 95% confidence interval (CI) 1.147-7.058; p = 0.024], a family history of atopy (OR 2.881 and 95% CI 1.240-6.692; p = 0.014), a serum tIgE level ≥965 kU/l (OR 5.917 and 95% CI 2.320-15.089; p = 0.000) and an sIgE/tIgE ratio ≥6% (OR 0.336 and 95% CI 0.124-0.911; p = 0.032). The sensitivity and specificity of the area under the curve of the serum tIgE were higher than those of serum sIgE and sIgE/tIgE ratio alone., Conclusion: Tobacco smoke exposure, atopic family history, serum tIgE and sIgE/tIgE ratio were in significant correlation with clinical response to AIT in children, which may be helpful for patient selection before immunotherapy. The serum tIgE is superior to both the serum sIgE/tIgE ratio and sIgE levels alone in predicting clinical effectiveness., (© 2014 S. Karger AG, Basel.)

Background: Standardized allergen-specific immunotherapy (SIT) has been used in China for years. However, there is no extensive study of the safety of standardized SIT in Chinese patients until now. The aim of the current study is to perform a prospective and multicenter study to evaluate the systemic reactions (SRs) of standardized SIT in Chinese patients., Methods: The study was performed in 13 allergy centers in China, using the same vaccine and practice procedure. The length of observation period was 2 years. SRs were recorded and analyzed., Results: There were 666 patients included (261 children and 405 adults). All patients finished the initial phase and 47 patients withdrew during the maintenance phase. There were 0.47% (94/19,963) SRs in all injections (0.72% in children and 0.31% in adults); 8.26% (55/666) patients experienced SRs (12.26% children and 5.68% adults). The occurrence of SRs was significantly higher in children than that in adults (p < 0.01). A higher ratio of SRs was found among patients accompanied with asthma. There were 74.47% SRs of grade I, 15.96% SRs of grade II, 7.45% SRs of grade III, and 2.13% SRs of grade IV. There were 90.43% of SRs associated with the discomfort of lower respiratory tract., Conclusion: This multicenter study showed that properly conducted standardized SIT was a safe treatment for allergic rhinitis in China. The incidence of SRs was higher in children than that in adults.

Introduction: The clinical efficacy of sublingual immunotherapy (SLIT) has already been proven and is known to be high. Its influence on the immunological system of patients suffering from bronchial asthma was also examined. However, it is still unclear how the polysensitisation, coexistence of other atopic disease and asthma treatment step influence the response to treatment with specific immunotherapy. Herein we evaluate the impact of one-year SLIT on selected markers of immunological response depending on different individual and clinical factors of children suffering from atopic asthma and allergic rhinitis., Material and Methods: Twenty-five patients aged 8.1 ± 3.1 years (range 5-15 years), 21 boys and 4 girls, suffering from asthma and allergic rhinitis with polysensitisation to seasonal and non-seasonal allergens, shortlisted for SLIT, were included in the study. Th1 cell and Th2 cell percentages, Bcl-2 expression in T cells, and basophil activation after allergen challenge (house dust mite and/or grass pollen antigen in solution used for skin prick tests) in peripheral blood were measured using flow cytometry. The association between clinical features of asthma and the influence of SLIT on immunological parameters was evaluated with exact Fisher test., Results: No association between the influence of one-year sublingual immunotherapy on immunological system and patients' age, polysensitisation, asthma treatment step, or coexistence of any other atopic diseases was observed. However, an increase of the Th1 percentage in children sensitised against more than three allergens was found more often (at the limit of statistical significance) than in the group of children sensitised against three or less allergens., Conclusions: Based on our results, we cannot point to any subgroup isolated in the study, in which the response of the immunological system to sublingual immunotherapy is more satisfactory than any other. Nevertheless, the increase of Th1 cells may be more specific for polysensitised children.

Background: There are few studies which analyse the characteristics of allergic respiratory disease according to profiles of sensitisation to different allergens. This study describes the clinical features and therapeutic approaches, according to the sensitisation profile to relevant aeroallergens, in a sample of adult patients with a first-time diagnosis of respiratory allergy (rhinitis and/or asthma)., Methods: 1287 patients, enrolled consecutively in the spring of 2010 by 200 allergy specialists, were classified into four groups according to sensitisation to significant allergens in each geographical area (grass pollen, olive pollen, grass and olive pollen, house dust mites). Information was obtained on demographics, diagnostic procedures used, treatments prescribed, clinical characteristics of the rhinitis, and severity and control of asthma., Results: Of the patients, 58.6% had rhinitis only and 38.7% had both rhinitis and asthma. Patients with more severe rhinitis had more severe and poorer controlled asthma. Sensitisation to different allergens was not associated with significant differences in severity and control of asthma, but patients with house dust mite allergy presented persistent rhinitis more frequently. Allergy to grass pollen was significantly associated with food allergies. Differences were observed in the frequency of prescription of immunotherapy and antileukotrienes in patients allergic to house dust mites and of topical corticosteroids in patients with pollen allergy., Conclusions: It was observed in this study that in respiratory allergy disease, there are clinical differences as well as differences in diagnostic procedure and therapeutic attitudes, depending on the clinically relevant allergen., (Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.)

The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.

Purpose of Review: Sublingual immunotherapy (SLIT) is effective in allergic rhinitis and asthma. Apart from its efficacy, safety is crucial as this treatment is usually self-administered at home. Tolerability also plays a pivotal role, as mild local reactions, although not life-threatening, may represent a risk for treatment withdrawal and can therefore negatively affect clinical outcomes. The present study addresses this issue by reviewing double-blind, placebo-controlled, randomized trials and real-life studies., Recent Findings: The number of life-threatening SLIT-related reactions is negligible. SLIT-related adverse events are not always consistently reported nor uniformly classified in published studies. However, systemic reactions are rare and side effects mostly consist of mild, self-limiting local reactions. No treatment-related risk factors for adverse events have been clearly defined, as far as type of allergen, dose or schedule., Summary: SLIT provides an optimal safety profile both in children and in adults. Apart from life-threatening reactions, the lack of standardization of adverse events reporting may account for the wide variability of the prevalence of side effects in clinical trials and in real-life setting. It can lead to a possible underestimation of adverse events, concerning, in particular, local reactions. Since poor tolerability may affect adherence and cause treatment discontinuation, adopting shared strategies in order to recognize, grade and manage adverse events is mandatory.

Introduction: There is an increasing prevalence of atopic diseases such as allergic rhinitis and asthma with house dust mite (HDM) being the common allergen that is highly associated with allergic rhinitis and asthma. Allergen avoidance and pharmacotherapy are part of treatment but it has proved difficult to change the course of HDM-related allergic diseases. Allergen immunotherapy (AIT) has been in use for the past century and has been shown to be effective in the treatment of allergic respiratory disease., Areas Covered: This review exclusively focuses on HDM-AIT and discusses the differences in clinical efficacy and safety, long-term effect after discontinuation and immunological changes observed in both HDM-subcutaneous immunotherapy (SCIT) and HDM-sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis and asthma in both pediatric and adult populations., Expert Opinion: The majority of studies involved small numbers of patients, variable doses of major allergens and are of variable quality. There is good evidence for HDM-SCIT efficacy and its long-term effect in adults and children, whereas at the present time, evidence for HDM-SLIT is unconvincing, particularly in children. In carefully selected patients, HDM-SCIT is effective and safe. More definitive trials are needed before HDM-SLIT can be recommended in routine practice for rhinitis and/or asthma.

Immunotherapy can be administered either sublingually (sublingual immunotherapy [SLIT]) or subcutaneously (subcutaneous immunotherapy [SCIT]). The rate of route switching, required by patients, can provide an indirect evaluation of patients' preferences and adherence. The authors retrospectively reviewed patients' files over an 18-year period to quantify the changes in the route of administration. The clinical records of children referred for respiratory allergy between 1994 and 2011 and prescribed with SLIT or SCIT were reviewed. The specific causes of the shift from SLIT to SCIT and vice versa were always assessed, with a special attention to adverse events. The records of 4933 children (2289 male patients, aged 4-18 years) were reviewed. Six hundred forty-eight patients received SCIT and 4285 patients received SLIT. Of the 4285 SLIT patients, 340 (7.9%) shifted to SCIT, mainly with Parietaria judaica and grasses. The 85.8% of the changes were caused by a perceived low efficacy. None of the parents required the route change for side effects. Of the 648 patients initially treated with SCIT, 54 (8.3%) shifted to SLIT, 85% of them for local or systemic side effects, but none for poor efficacy. The rate of SCIT/SLIT changes is, overall, low and because of poor efficacy for SLIT and side effects for SCIT.

Objective: To evaluate the efficacy of specific sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops on children with allergic asthma and allergic rhinitis of the preschool and school-age groups of children and adolescents., Method: This study analyzed the efficacy of SLIT in 122 children (aged 3-14 yr) with house dust mites-induced allergic asthma and allergic rhinitis. According to the age, patients were defined as the preschool group ( ≤ 6 years old, n = 59) and school-age group (> 6 years old, n = 63). All children were treated with Dermatophagoides farinae drops for at least 2 years. Clinical observation and follow-up study were conducted during the treatment. Before and after SLIT for half a year, 1 year and 2 years, asthma symptom scores (day and night), rhinitis symptom scores and medication scores were evaluated. The adverse events were assessed during the study., Result: After SLIT for half a year, 1 year and 2 years, there were no significant differences between the preschool group (0.3 ± 0.5,0.0 ± 0.1,0.0 ± 0.0) and school-age group (0.3 ± 0.4,0.0 ± 0.1,0.0 ± 0.0) in day scores of asthma (Z value was -1.687, -0.613,0.000, all P > 0.05). There were no significant differences between the preschool group (0.2 ± 0.5,0.1 ± 0.3,0.0 ± 0.0) and school-age group (0.2 ± 0.4,0.1 ± 0.3, 0.0 ± 0.0) in night scores of asthma (Z value was -0.496, -0.486,0.000, all P > 0.05). There was no significant differences between the preschool group (1.4 ± 0.9,0.4 ± 0.5,0.1 ± 0.3) and school-age group (1.3 ± 0.9,0.5 ± 0.6,0.2 ± 0.4) in symptom scores of allergic rhinitis (Z value was -0.394, -1.166, -1.075, all P > 0.05). There were no significant differences between the preschool group (1.6 ± 0.8,0.0 ± 0.0,0.0 ± 0.0) and school-age group (1.7 ± 0.7,0.0 ± 0.0,0.0 ± 0.0) in medication scores of allergic rhinitis (Z value was -0.655,0.000,0.000, all P > 0.05). After SLIT for 2 years, most children in the preschool and school-age groups were no longer using asthma controlling medication, with no significant difference between the two groups (Z value was 0.000, P > 0.05). The overall incidence of adverse reactions was only 7%, and there was no significant difference in the incidence of adverse reactions between the two groups (χ(2) = 0.000, P > 0.05). The local adverse events were mild gastrointestinal discomfort and rash, a majority of local adverse events in the preschool group were diarrhea. No severe adverse events happened in the treatment., Conclusion: SLIT with Dermatophagoides farinae drops is safe and effective in children with allergic asthma and allergic rhinitis of the preschool and school-age groups of children and adolescents, which provides evidences for early SLIT intervention of the disease.

Allergic rhinitis and asthma represent global problems of public health affecting all age groups; asthma and allergic rhinitis frequently coexist in the same patients. In Latin American prevalence of allergic rhinitis, although variable, is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a workshop of the World Health Organization performed in 1999 and was published in 2001. ARIA proposed a new classification of allergic rhinitis in intermittent or persistent and mild or moderate-severe. This approach of classification reflects more nearly the impact of allergic rhinitis in patients. In its review of 2010 ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of clinical practices for management of comorbidities of allergic rhinitis and asthma based on GRADE (Grading of Recommendations, Development and Evaluation). ARIA has been spread and implemented in more than 50 countries. In Latin American an intense activity has been developed to spread these recommendations in almost all the countries of the region and it is important to record the obtained goals in the diffusion and implementation of ARIA, as well as to identify the unsatisfied needs from the clinical, research and implementation points of view. Final objective is to reinforce the priority that allergy and asthma should have, especially in children, in the programs of public health, as they have been prioritized in European Union in 2011.

The present study included 73 patients presenting with bronchial asthma (BA) and concomitant allergic rhinitis (AR). Based on the results of their examination, a program of their two-step treatment was proposed including elimination therapy during 5-7 days followed by the combined treatment with the use of physical factors, such as peloid therapy, supratonal frequency currents, inhalations, massage, and remedial gymnastics. This approach allows to significantly reduce the frequency of clinical manifestations of the primary and concomitant diseases. Specifically, the incidence of daytime choking fits decreased by 66.7%, coughing by 76.7%, nasal stiffness by 60%, and rhinorrhea by 62,6 with the simultaneous acceleration of the overall clinical effect by 3-4 days. The requirement for short-acting broncholytic agents decreased after the treatment by 56.7%. Its anti-inflammatory effect in the upper and lower respiratory tract was confirmed by the results of endoscopic examination of the nasal cavity (the occurrence of mucosal hyperemia and mucosal oedema decreased by 70% and 60% respectively whereas the presence of secretion in the nasal passages was recorded 76.7% less frequently than prior to the treatment). Cytological studies of surface epithelium revealed reduced neutrophilia and eosinophilia, decreased number of goblet cells in nasal mucosa, and lowered content of sialic acids, IL-1, and IL-6 in nasal lavage. Combined therapy improved the patency of both upper and lower respiratory tract. Moreover, the number of patients with the totally controlled clinical course of BA increased by 66.6%. It was shown that remission of BA and AR persisted within 10 and 8.2 months after the treatment respectively.

Background: Both SCIT (subcutaneous immunotherapy) and SLIT (sublingual immunotherapy) have clinical and immunologic efficacy in children with rhinitis and asthma but comparative studies are scarce., Objective: To investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT in children with rhinitis and asthma., Method: Thirty children monosensitized to house dust mite were randomized to receive either active SCIT or SLIT or placebo for 1 yr in a double-blind double-dummy placebo controlled design (Yukselen A et al., Int Arch Allergy Immunol 2012; 157:288-298). Thereafter, the placebo group was randomized to receive SCIT or SLIT, and for 1 yr all patients received active treatment with SCIT or SLIT. Symptom scores, drug usage, titrated skin prick tests, nasal and bronchial allergen provocation doses, serum house dust mite-specific immunglobulin E, sIgG4, IL-10 and IFN- g levels were evaluated., Results: The reduction of clinical scores with SLIT was more evident after 2 years of treatment in comparison to both the baseline and DBPC phase of the study. The change in titrated skin prick tests and nasal provocative doses was more prominent with both SCIT and SLIT at the end of the open phase. Although the increase inbronchial provocative doses was not significant at the end of the first year of treatment with SLIT, it reached a statistically significant difference after two years of treatment., Conclusion: The clinical efficacy of SLIT is more prominent at the end of the second year, although this improvement is observed from the first year of treatment with SCIT in mite-sensitive children.

Objective: To investigate the cost-effectiveness of standardized specific immunotherapy (SIT) for allergic rhinitis patients accompanied with asthma (ARAS) in China., Method: Forty ARAS patients sensitized with house dust mite (HDM) were administered with SIT (SIT group) or merely medicine treatment (control group). Alutard dermatophagoides pteronyssinus vaccine from ALK company was used for immunotherapy. The usage of symptom control medicine was according to the ARIA and GINA guideline. Cost-effectiveness ratio (CER) and Incremental cost-effectiveness ratio(ICER) analysis was conducted. The effectiveness was measured in terms of symptom scores, quality of life, objective improvement of rhinitis and asthma. Sensitive analysis was conducted to verify the stability of the results., Result: The cost of SIT group for 1 year (6578 yuan) was higher than that of control group (1733.3 yuan), while the cost-effectiveness ratio and incremental cost-effectiveness ratio of SIT group were significant better than that of control group in all items. CER was 1686.7 yuan in SIT group compared with 3466.6 yuan in control group for nasal symptom scores, 4698.6 yuan in SIT group compared with 5777.8 yuan in control group for asthma symptom scores, 3462.1 yuan in SIT group compared with 8666.7 yuan in control group. The sensitive analysis of the price 10 percent higher or lower showed the same results., Conclusion: The cost-effectiveness of specific immunotherapy (SIT) for mite sensitized ARAS patients was better than that of merely medicine treatment.

Background: Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies., Aim: We performed a case-control study to evaluate the effect of SLIT in children with allergic asthma and rhinitis., Patients and Methods: The study plan included 140 patients (age 6-14 yr, 43% girls and 57% boys) presenting allergic rhinitis and/or asthma, 70 treated with SLIT actively for three years and 70 controls never treated with specific immunotherapy (only symptomatic drugs). Rhinitis Symptom Score (RSS), Asthma Symptom Score (ASS) and Medication Score (MS) were evaluated at beginning and during the 3 years of immunotherapy. results: There was a significant improvement of RSS (mean ± SD) in the SLIT group: baseline 5.31 ± 2.01, third year 1.38 ± 1.06 (p < 0.0001 vs baseline)., Control Group: baseline 5.00 ± 1.08, third year 4.68 ± 1.152 (P ¼ NS). ASS (mean ± SD) in the SLIT group: baseline 4.09 ± 2.21, third year 1.23 ± 1.4 (p < 0.0001 vs baseline)., Control Group: baseline 4.04 ± 2.46, third year 3.62 ± 2.26 (p ¼ NS). MS (mean ± SD) in the SLIT group: baseline 3.30 ± 1.4, third year 0.88 ± 1.26 (p < 0.0001 vs baseline)., Control Group: baseline 3.19 ± 1.23, third year 3.39 ± 1.12 (p ¼ NS). There are no statistically significant differences among monosensitized/polysensitized patients and at different age ranges. None of the patients included reported severe systemic reactions or anaphylaxis., Conclusions: During the treatment, the active group showed sustained reductions in mean asthma and rhinitis symptom scores when compared with controls to confirm the efficacy and safety of sublingual immunotherapy.

Purpose of Review: The aim of this review is to update readers on the growing impact of a molecular approach (CRD) to the diagnosis and treatment of children with respiratory allergies, Recent Findings: A large panel of highly purified natural or recombinant species-specific and cross-reacting allergenic molecules is now available for clinical purposes. Species-specific molecules allow identifying specific sensitization toward a given allergenic source. Cross-reacting molecules allow interpreting polysensitization patterns that cannot be detailed using routine skin prick tests or specific IgE tests based on allergenic extracts. These molecular tools are transforming and improving the interpretation of clinical and laboratory tests used to define patients' IgE-sensitization profile., Summary: The accurate dissection of the IgE repertoire offers new possibilities in the diagnosis, prophylaxis and treatment of pediatric allergic rhinoconjunctivitis and asthma.

Objective: To examine the difference between children and their parents in reporting symptoms and treatment of allergic diseases within a longitudinal birth cohort., Study Design and Setting: Information on symptoms and treatment of asthma, rhinitis, and eczema was obtained by questionnaire from 2,744 children (mean age: 12 years) and their parents. Differences between the responses were computed, and agreement assessed both absolutely and with kappa coefficient., Results: On 12 of the 15 questions, children's and parents' reports differed significantly. Asthma-related issues appeared significantly more prevalent in the children's reports, although kappa values were fair to very good. For symptoms of allergic rhinitis, the prevalence pattern varied, and kappa values were moderate to good. Parents reported a higher prevalence of eczema-related issues, but the children reported a significantly higher prevalence of eczema itself. Kappa values ranged from moderate to good., Conclusion: Although reports of allergic symptoms and treatment by 12-year-old children and their parents were in moderate-to-good agreement, children reported more symptoms than their parents. Symptoms of allergic disease should be reported by children themselves, from the age of 11 years, whereas questions of prescribed pharmacological treatment could be answered either by the children or their parents., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Allergen-specific immunotherapy is widely used in the management of patients with allergic rhinoconjunctivitis and asthma, but the best route of delivery is unclear., Objective: We performed a systematic review of studies with head-to-head comparison of effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in the treatment of allergic rhinoconjunctivitis and asthma., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched through December 21, 2012. We included English language randomized controlled trials that enrolled patients with allergic rhinoconjunctivitis and/or asthma with head-to-head comparisons of SCIT with SLIT. Paired reviewers extracted detailed information from included articles on standardized forms and assessed the risk of bias in each article., Results: Eight trials compared the effectiveness and safety of SCIT and SLIT. The effectiveness of the 2 forms of immunotherapy in managing allergic asthma and rhinoconjunctivitis were reported in 4 and 6 clinical trials, respectively. Low-grade evidence supports greater effectiveness of SCIT than SLIT for asthma symptom reduction and also at reducing a combined measure of rhinitis symptoms and medication use. Moderate-grade evidence supports greater effectiveness of SCIT than SLIT for nasal and/or eye symptom reduction. All 8 trials reported on adverse events with an episode of anaphylaxis reported in a child treated with SCIT., Conclusion: Our review provides low-grade evidence to support that SCIT is superior to SLIT for reduction in asthma symptoms and moderate-grade evidence for reduction of allergic rhinoconjunctivitis. Additional studies are required to strengthen this evidence base for clinical decision making., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Respiratory allergies represent a global and public health problem, due to their prevalence (still increasing), morbidity, impact on the quality of life and costs for the society. They mainly concern rhinitis (or rhinoconjunctivitis) and asthma. The diagnosis of allergy is dependent on a history of symptoms on exposure to an allergen together with the detection of allergen-specific IgE. Accurate diagnosis of allergies opens up therapeutic options that are otherwise not appropriate, such as allergen immunotherapy and allergen avoidance, that are prescribed following a stepwise approach. It has been a century since the first trial in specific immunotherapy was performed and this still remains the only disease modifying treatment for allergic individuals. In terms of route of administration, sublingual immunotherapy represents a good alternative to subcutaneous immunotherapy, considering its proven efficacy and better safety profile., (Copyright © 2012. Published by Elsevier Masson SAS.)

Allergen immunotherapy (AIT) is effective in reducing the clinical symptoms associated with allergic rhinitis, asthma and venom-induced anaphylaxis. Subcutaneous (SCIT) and sublingual immunotherapy (SLIT) with unmodified allergen extracts are the most widely prescribed AIT regimens. The efficacy of these 2 routes appears comparable, but the safety profile with SLIT is more favorable allowing for home administration and requiring less patient time. However, both require that the treatment is taken regularly over several years, e.g., monthly in a supervised medical setting with SCIT and daily at home with SLIT. Despite the difference in treatment settings, poor adherence has been reported with both routes. Emerging evidence suggests that AIT may be effective in other allergic conditions such as atopic dermatitis, venom sting-induced large local reactions, and food allergy. Research with oral immunotherapy (OIT) for food allergies suggest that many patients can be desensitized during treatment, but questions remain about whether this can produce long term tolerance. Further studies are needed to identify appropriate patients and treatment regimens with these conditions. Efforts to develop safer and more effective AIT for inhalant allergies have led to investigations with modified allergens and alternate routes. Intralymphatic (ILIT) has been shown to produce long-lasting clinical benefits after three injections comparable to a 3-year course of SCIT. Epicutaneous (EPIT) has demonstrated promising results for food and inhalant allergies. Vaccine modifications, such as T cell epitopes or the use of viral-like particles as an adjuvant, have been shown to provide sustained clinical benefits after a relatively short course of treatment compared to the currently available AIT treatments, SLIT and SCIT. These newer approaches may increase the utilization and adherence to AIT because the multi-year treatment requirement of currently available AIT is a likely deterrent for initiating and adhering to treatment.

Purpose of Review: Allergic rhinitis, chronic rhinosinusitis (CRS) and asthma have a high worldwide prevalence and confer a significant socioeconomic burden. This article reviews the recent advances in allergic rhinitis, CRS and asthma with view to understanding the upper and lower airway as one system., Recent Findings: Allergic rhinitis, CRS and asthma demonstrate strong epidemiological coassociation, and early life risk factors for upper airway disease are now apparent. The absence of demonstrable peripheral IgE does not strictly classify airway disease as nonallergic. Excess mucosal inflammation with immune dysregulation is a common feature to all. An important role for innate immunity is now apparent and offers prospects of novel therapeutic approaches in the future. A role for bacterial superantigens is also emerging in all three diseases. Genetic studies highlight common associations between allergic rhinitis, CRS and asthma., Summary: Whether such overlapping pathological findings reflect a manifestation of the same disease but in relation to the different airway locations in individuals with genetic predisposition remains unknown, although likely. This continues under investigation and debate. The current research priorities are to understand what key events predispose to both upper and lower airway disease together and the critical immunological factors that establish and sustain airway inflammation.

Allergen-specific immunotherapy administered by the subcutaneous route was introduced a century ago and has been shown to be effective in the management of allergic rhinitis and asthma. More recently, the sublingual administration of allergen extracts has become popular, especially in European countries, and has also demonstrated efficacy in respiratory allergic diseases. Both modes of allergen administration during immunotherapy have been shown not only to reduce symptoms and the need for medication, but also to prevent the development of additional sensitivities in monosensitized patients, as well as asthma development in patients with allergic rhinitis, with a long-lasting effect after the completion of several years of treatment. Almost all of the well-designed and double-blinded, placebo-controlled studies evaluated treatment with single-allergen extracts. Therefore, most meta-analyses published to date evaluated immunotherapy with single allergen or extracts containing several cross-reactive allergens. As a result, in general, multiallergen immunotherapy in polysensitized patients (mixture of noncross-reactive allergens) is not recommended owing to lack of evidence. Although some guidelines have recommended against the use of multiallergen mixtures, allergists commonly use mixtures to which the patient is sensitive with the rationale that effective immunotherapy should include all major sensitivities. Literature on this subject is scarce in spite of the widespread use worldwide. Here, this issue will be extensively discussed based on currently available literature and future perspectives will also be explored.

Background: Specific IgG4 induced by allergen-specific immunotherapy (SIT) is an immunological marker related to the appearance of clinical tolerance. But specific IgG4 levels in different age, gender and allergic disease populations have not been fully investigated., Methods: This study involved 226 children and 109 adults with allergic rhinitis and/or asthma receiving a 156-week course of Dermatophagoides pteronyssinus (Der p) subcutaneous SIT. Symptom and medication scores, forced expiratory volume after 1 s (FEV(1)) and Der p-specific IgG4 levels at weeks 0, 5, 10, 25, 52, 104 and 156 were analyzed., Results: Rhinitis symptom and medication scores and FEV(1) % predicted in children showed significantly greater improvement than in adults at week 104 and 156 (p < 0.05). Levels of Der p-specific IgG4 showed a significant increase after 10 weeks of subcutaneous SIT (p < 0.0001) and continued to increase during the 156-week SIT period. Before SIT, the initial Der p-specific IgG4 level was higher in children than adults (p = 0.0004). The increase ratio of Der p-specific IgG4 was higher in children than adults at 52 weeks (p < 0.001) and 104 weeks (p = 0.0156) of SIT, and was higher in rhinitis compared to asthma patients at 156 weeks of SIT (p = 0.0244). There was no difference between males and females at any time points., Conclusion: Children are more responsive to SIT, demonstrating clinical and FEV(1) improvement and producing higher levels of allergen-specific IgG4 during a shorter SIT period compared to adults. Rhinitis patients show a higher increase in specific IgG4 compared to patients with asthma symptoms. The increase of Der p-specific IgG4 reflects a specific response of the immune system towards the SIT vaccine being administrated., (Copyright © 2012 S. Karger AG, Basel.)

Background: Climatic changes causing early pollen flight and new allergens prolonging the pollen season render up-dosing of allergen-specific subcutaneous immunotherapy (SCIT) outside the pollen season considerably more difficult. In addition, for patients with multiple pollen allergies, patients coming near the beginning of pollen season, and patients who wish to up-dose faster, an accelerated induction regimen would be helpful., Methods: In an open, randomized, parallel group, multicenter safety trial, an accelerated up-dosing regimen (0.1-0.3-0.5 ml in weekly intervals) was compared to conventional up-dosing (0.05-0.1-0.2-0.3-0.4-0.5 ml in weekly intervals) with an allergoid grass pollen SCIT preparation. After up-dosing, the maintenance dose was given in monthly intervals., Results: A total of 146 adult patients with rhinitis or rhinoconjunctivitis with or without mild asthma (FEV1 >70%) due to grass pollen were randomized to either the conventional registered up-dosing or an accelerated regimen. In both groups (accelerated regimen, n = 69; conventional regimen, n = 75), a high proportion of patients (92.75 and 92.0%, respectively) successfully reached the maintenance dose without safety concerns. Furthermore, significant increases in specific IgG and IgG4 after 4 months of treatment were observed in both groups., Conclusion: The accelerated SCIT regimen was found to be as safe as the conventional regimen and might be used to up-dose patients within 2 weeks. Moreover, the immunological effects of both up-dosing regimens were comparable., (Copyright © 2012 S. Karger AG, Basel.)

Some of the most recent advances in the diagnosis and treatment of childhood asthma and allergies are here reviewed. New perspectives have been opened by in vitro diagnostic tests for allergies based on a molecular approach and novel approaches to in vivo tests (SPT or FE(NO)). A better characterization of the patients is opening new classifications of allergic asthma and rhinitis phenotypes, which allow personalizing management disease programs and targeting pharmacotherapy. Educational programs and better communication are improving awareness and compliance with medical prescriptions and adherence to guidelines. Increasing information is being acquired on the mechanisms, efficacy and safety profiles of anti-asthma and anti-allergic drugs, including antihistamines, inhaled corticosteroids, long acting beta agonists, antibiotics, anti-IgE antibodies. Progress in biotechnologies is fostering new approaches to allergen-specific immunotherapy (subcutaneous, sublingual) concerning the quality, mechanisms, efficacy and safety of allergen products.