Background
To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on ...the effectiveness, cost‐effectiveness and safety of AIT.
Methods
We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random‐effects meta‐analyses.
Results
98 studies satisfied the inclusion criteria. Short‐term symptom scores were reduced with a standardized mean difference (SMD) of −1.11 (95% CI −1.66, −0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short‐term medication scores were reduced SMD −1.21 (95% CI −1.87, −0.54), again with evidence of potential publication bias. There was no reduction in short‐term combined medication and symptom scores SMD 0.17 (95% CI −0.23, 0.58), but one study showed a beneficial long‐term effect.
For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen‐specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR.
AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported.
The limited evidence on cost‐effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost‐effective.
Conclusions
AIT can achieve substantial reductions in short‐term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer‐term effectiveness and cost‐effectiveness.
The prevalence of allergic diseases has significantly increased in industrialized countries. Allergen-specific immunotherapy (AIT) remains as the only curative treatment. The knowledge about the ...mechanisms underlying healthy immune responses to allergens, the development of allergic reactions and restoration of appropriate immune responses to allergens has significantly improved over the last decades. It is now well-accepted that the generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are essential for healthy immune responses to environmental proteins and successful AIT. Treg cells comprise different subsets of T cells with suppressive capacity, which control the development and maintenance of allergic diseases by various ways of action. Molecular mechanisms of generation of Treg cells, the identification of novel immunological organs, where this might occur in vivo, such as tonsils, and related epigenetic mechanisms are starting to be deciphered. The key role played by the suppressor cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β produced by functional Treg cells during the generation of immune tolerance to allergens is now well established. Treg and Breg cells together have a role in suppression of IgE and induction of IgG4 isotype allergen-specific antibodies particularly mediated by IL-10. Other cell types such as subsets of dendritic cells, NK-T cells and natural killer cells producing high levels of IL-10 may also contribute to the generation of healthy immune responses to allergens. In conclusion, better understanding of the immune regulatory mechanisms operating at different stages of allergic diseases will significantly help the development of better diagnostic and predictive biomarkers and therapeutic interventions.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently administered drugs, mainly for their antipyretic, but also for pain-relieving and anti-inflammatory effects in children. ...NSAIDs are composed of structurally divergent subgroups of drugs with similar pharmacological and adverse effects. Aspirin originates from salicin and was the first synthesized analgesic. As a prototype of NSAIDs; aspirin-induced hypersensitivity reactions were first reported, but subsequently, other phenotypes of hypersensitivity reactions were also described with aspirin and other NSAIDs. There are certain challenging aspects of NSAID-hypersensitivity in the pediatric population that need to be further investigated. These include the effect of age on drug metabolism and the natural history of the various phenotypes of NSAID-hypersensitivity, the effect of certain co-factors (infections, exercise) on NSAID-hypersensitivity, and diagnostic clinical and laboratory biomarkers clarifying the endotypes. In recent years, a non-negligible number of case series, studies and expert panel reports have been published in this field with some novel features and diagnostic modalities in the pediatric population. With the current review; the clinical phenotypes and diagnostic and management modalities of suspected NSAID-induced hypersensitivity reactions in childhood and adolescence were explained and updated by examining past and current publications. Keywords: allergy, aspirin, child, drug, ibuprofen, paracetamol
A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT ...levels and IgE‐mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n = 167) were analyzed in two groups according to the presence (FA+/A+; n = 79) or absence of anaphylaxis (FA+/A−; n = 88) and were compared with a control group (n = 113). Median sBT values in FA+/A+, FA+/A−, and control groups were 4.0 ng/ml (2.8–5.8), 3.6 (2.3–4.5), and 3.3 (2.4–4.4), respectively (P = 0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P = 0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.
Background
Indoleamine 2,3‐dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in ...food allergy has not yet been elucidated.
Methods
Serum Trp and Kyn concentrations were analyzed by high‐pressure liquid chromatography. Expression of IDO gene was measured by real‐time PCR. The levels of interleukin (IL)‐4, IL‐10, and interferon (IFN)‐γ in cell culture supernatants were measured by ELISA.
Results
Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged‐matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04 (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food‐allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL‐4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL‐10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN‐γ synthesis, when stimulated with IL‐2 and β‐lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively).
Conclusion
Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.
Abstract Asthma is a complex, chronic inflammatory disease of the lower airways affecting people of all ages. Approximately 300 million individuals are currently suffering from asthma worldwide. The ...prevalence of asthma is estimated to range from 3% to 38% in children and from 2% to 12% in adults. The disease causes lost school and work days, limitations in daily activities, and sleep disturbances. Lung function impairment also occurs, resulting in decreased quality of life unless disease control is achieved and a high annual financial burden is incurred. Achievement and maintenance of control through assessment of clinical manifestations and future risk has become the aim of treatment over the years. Unfortunately, the desired level of asthma control has not been achieved in a considerable number of regions throughout the world, and the level of control is overestimated by both patients and their parents. This review examines the mortality and morbidity rates for asthma, emphasizes the challenges inherent to control management, and provides data on the tools used to measure control level.
To analyse the demographics, main clinical and laboratory features and subtype distribution of juvenile idiopathic arthritis (JIA) in an eastern Mediterranean country, based on a multicentre ...registry.
Between March 2008 and February 2009 with this cross-sectional study, consecutive patients seen with JIA in selected centres were registered through a web-based registry. All patients were classified according to the International League of Associations for Rheumatology (ILAR) criteria.
There were 634 patients with a mean age of 11.84 ± 4.66 years and the female/male ratio was 1.2. The distributions of JIA patients according to onset of disease were as follows: systemic 92 (14.5%), oligoarticular extended 26 (4.1%), oligoarticular persistent 234 (36.9%), rheumatoid factor (RF) positive polyarthritis 20 (3.2%), RF negative polyarthritis 129 (20.3%), enthesitis-related 120 (18.9%), psoriatic 13(2.1%). The frequency of uveitis was 15.7% among all of the oligoarthritis patients. Anti-nuclear antibody (ANA) was positive mainly among the oligoarticular onset patients. Twenty-one patients also had Familial Mediterranean fever (FMF). Among systemic JIA patients, the frequency of macrophage activation syndrome (MAS) was 15.2% (n=14). At the end of the mean follow-up of 7.6 ± 4.4 years, 305 (48.1%) patients were defined to have inactive disease on medication, and 106 (16.7%) were completely free of any disease symptoms without medication.
Enthesitis related arthritis had a high frequency whereas psoriatic arthritis was very rare compared to other series. We suggest that there are certain differences in the characteristics of JIA in our eastern Mediterranean population. Thus, genetic studies need to be assessed in these populations separately and findings of genome wide association studies need to be confirmed in different populations.
Abstract Background Drug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug ...allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. Methods Medical records covering the period of 2005–2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. Results Ninety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests ( n = 11) and drug provocation tests ( n = 5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%, p = 0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p = 0.001). The patients’ history of anaphylaxis OR: 5.789, 95%CI: 1.880–17.554, p = 0.002, sweating OR: 7.8, 95%CI: 1.041–58.443, p = 0.046 and dyspnoea OR: 5.230, 95%CI: 1.836–14.894, p = 0.002 during suspicious DHRs increased the risk for actual drug allergy. Conclusion Actual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy.
Background
Asthma‐like symptoms in preschool children, such as wheezing and dyspnea, are common time‐ and resource‐consuming diagnostic and management challenges. Quality of wheezing and asthma ...recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma.
Methods
The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.
Results
We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%.
Conclusion
Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non‐asthmatic preschool wheeze.
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