Molecular Diagnosis in House Dust Mite-Allergic Patients Suggests That Der p 23 Is Clinically Relevant in Asthmatic Children.

BACKGROUND: Patterns of sensitization to house dust mites depend on geographic area and are important in clinical practice. However, the role of molecular diagnosis is not currently defined. We sought to characterize a pediatric population by focusing on sensitization to different mite species and major mite components in order to assess the clinical relevance of sensitization to allergenic components in our practice. METHODS: Consecutive children with respiratory allergy sensitized to house dust mites (determined by skin prick test [SPT]) were recruited. We determined specific IgE to nDer p 1, rDer p 2, and rDer p 23 using ImmunoCAP and sIgE using ImmunoCAP-ISAC microarray. Patients were followed up for 3 years. RESULTS: A total of 276 children were recruited. The frequency of sensitization was 86.6% for nDer p 1, 79.3% for rDer p 2, and 75.8% for rDer p 23. Lepidoglyphus species was the most common storage mite detected by SPT. Twenty-six patients (9.4%) were not sensitized to Der p 1 or Der p 2. It is noteworthy that IgE binding to Der p 23 was positive in 14 (53.8%). Asthmatic patients, especially those with a persistent moderate-severe phenotype, more frequently recognized the 3 major allergens. CONCLUSIONS: Most patients with mite allergy were sensitized to the major allergens Der p 1, Der p 2, and Der p 23. Of the allergens evaluated, 5% were sensitized to Der p 23 but not to Der p 1 or Der p 2. Sensitization to Der p 23 should be considered in the diagnosis and treatment of mite allergy, especially in patients with moderate-severe asthma, because it may worsen the clinical phenotype.

Molecular diagnosis in house dust mite-allergic patients suggests that Der p 23 is clinically relevant in asthmatic children

BACKGROUND: Patterns of sensitization to house dust mites depend on geographic area and are important in clinical practice. However, the role of molecular diagnosis is not currently defined. We sought to characterize a pediatric population by focusing on sensitization to different mite species and major mite components in order to assess the clinical relevance of sensitization to allergenic components in our practice. METHODS: Consecutive children with respiratory allergy sensitized to house dust mites (determined by skin prick test [SPT]) were recruited. We determined specific IgE to nDer p 1, rDer p 2, and rDer p 23 using ImmunoCAP and sIgE using ImmunoCAP-ISAC microarray. Patients were followed up for 3 years. RESULTS: A total of 276 children were recruited. The frequency of sensitization was 86.6% for nDer p 1, 79.3% for rDer p 2, and 75.8% for rDer p 23. Lepidoglyphus species was the most common storage mite detected by SPT. Twenty-six patients (9.4%) were not sensitized to Der p 1 or Der p 2. It is noteworthy that IgE binding to Der p 23 was positive in 14 (53.8%). Asthmatic patients, especially those with a persistent moderate-severe phenotype, more frequently recognized the 3 major allergens. CONCLUSIONS: Most patients with mite allergy were sensitized to the major allergens Der p 1, Der p 2, and Der p 23. Of the allergens evaluated, 5% were sensitized to Der p 23 but not to Der p 1 or Der p 2. Sensitization to Der p 23 should be considered in the diagnosis and treatment of mite allergy, especially in patients with moderate-severe asthma, because it may worsen the clinical phenotype

ANTECEDENTES: El perfil de sensibilización a los ácaros del polvo depende del área geográfica y es importante en la práctica clínica. Sin embargo, el papel del diagnóstico molecular no ha sido del todo definido. Nuestro objetivo fue la caracterización del perfil de sensibilización de una población pediátrica a diferentes especies de ácaros; y evaluar la sensibilización a componentes alergénicos y su relevancia en nuestra práctica clínica. MÉTODOS: Se reclutaron de forma consecutiva pacientes con alergia respiratoria y sensibilización a ácaros del polvo doméstico mediante pruebas cutáneas. Se determinó la IgE específica por ImmunoCAP a nDer p 1, rDer p 2, rDer p 23 y la sIgE mediante el microarray de ImmunoCAP ISAC. Los pacientes fueron evaluados durante tres años según práctica cínica habitual. RESULTADOS: Se reclutaron un total de 276 niños. La sensibilización fue de 86,6% a nDer p 1, 79,3% a rDer p 2 y 75,8% a rDer p 23. Lepidoglyphus fue el ácaro de almacén más común según prueba cutánea. Un total de veintiséis pacientes (9,4%) no estaban sensibilizados a Der p 1 ni Der p 2; cabe destacar que 14 de ellos (53,8%) presentaban IgE positiva a Der p 23. Los pacientes con asma, y en especial los de fenotipo persistente moderado y grave, reconocieron con mayor frecuencia los tres alérgenos mayores. CONCLUSIONES: La mayoría de nuestra población pediátrica con alergia a ácaros está sensibilizada a los alérgenos mayores Der p 1, Der p 2 y Der p 23. Un 5% estaba sensibilizado a Der p 23, pero no a Der p 1 ni a Der p 2. La sensibilización a Der p 23 debe considerarse en el diagnóstico y tratamiento de la alergia a ácaros, especialmente en pacientes con asma persistente moderada y grave

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. METHODS: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. RESULTS: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. CONCLUSIONS: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test.

BACKGROUND: Strict avoidance is the only accepted management for cow's milk (CM) allergy. CM oral immunotherapy (CM-OIT) is under investigation. OBJECTIVES: To evaluate long-term safety of CM-OIT. To identify clinical/immunological predictors of adverse events. METHODS: Prospective longitudinal epidemiological intervention study. CM-allergic children aged 5-18 underwent a Spanish-approved CM-OIT protocol without premedication. Clinical data, skin prick test (SPT) and specific IgE (sIgE) at baseline and 1 year after OIT were registered. All dose-related reactions, treatments needed and cofactors involved were recorded. Through survival analysis, we studied the cumulative probability of reactions resolution over time and clinical/immunological risk factors of reactions persistence. RESULTS: 81 children were recruited. Mean follow-up was 25 months. 95% of children suffered reactions, 91% of which affected a single organ. Reactions were heterogeneously distributed: (a) 60 children (75%) had occasional symptoms which ceased over time. 86% of them reached complete desensitization (200 mL). (b) 20 children (25%) suffered frequent (78% of total reactions), more severe and unpredictable reactions, which persisted during follow-up or led to withdrawal (6 cases). Reactions persistence was associated with a higher frequency and severity. Kaplan-Meier estimate revealed a cumulative probability of reactions resolution of 25% at 3 months (95% CI: 1.9-4.1) and 50% (95% CI: 6.1-9.9) at 8 months based on all patients. Cox proportional hazards multivariate regression model identified 3 variables (CM-sIgE ≥ 50 KU L(-1) , CM-SPT ≥ 9 mm and Sampson's severity grades 2, 3 and 4 at baseline food challenge) as independent risk factors of reactions persistence. The combination of 2 or 3 of these factors involved hazard ratios to develop persistent reactions of 2.26 (95% CI: 1.14-4.46; P = 0.019) and 6.06 (95% CI: 2.7-13.7; P < 0.001), respectively. CLINICAL IMPLICATIONS: CM-OIT was insufficiently safe in 25% of children. The above-mentioned clinical and immunological parameters would help clinicians to identify highly reactive patients before CM-OIT. In them, individualized schedules and premedication should be considered.

Estudio clínico y epidemiológico de las neumonías por Mycoplasma pneumoniae y adenovirus en un hospital de Barcelona / Clinical and epidemiological study of Mycoplasma pneumoniae and adenoviral pneumonia in a hospital of Barcelona

Introducción: Mycoplasma pneumoniae y adenovirus son dos de las causas más frecuentesde neumonía en la infancia. El objetivo del estudio es describir las características epidemiológicas,clínicas, radiológicas y analíticas de los casos de neumonía por dichos microorganismosen menores de 15 años en un hospital de Barcelona. Determinar si existen diferenciasentre etiologías y edades y conocer los casos de coinfección.Material y métodos: estudio retrospectivo, mediante revisión de las historias clínicas delos menores de 15 años atendidos en el periodo 2000-2007 en el hospital y cuya IgM paraM. pneumoniae y/o adenovirus fue positiva o se obtuvo inmunofluorescencia o cultivo positivopara adenovirus. Posteriormente se realizó un análisis estadístico mediante SPSS(R). Resultados: se diagnosticaron 153 neumonías: 73 por M. pneumoniae y 80 por adenovirus.La media de edad fue de 5,7 y 3,5 años respectivamente, siendo el 46% menores de 5 años en la neumonía por M. pneumoniae y el 71,3% por adenovirus. No se observó predominioestacional claro. Las manifestaciones clínicas más frecuentes fueron fiebre y tos, conbuen estado general. La auscultación pulmonar fue patológica en 141 casos, predominandola unilateralidad y crepitantes. La alteración radiológica fue mayoritariamente unilateral. Losresultados analíticos no fueron significativos. Se encontraron 23 coinfecciones entre ambos y 22 con otros microorganismos. Conclusiones: M. pneumoniae y adenovirus deben ser considerados como agentes causales de neumonías en cualquier edad de la infancia. Destaca la dificultad para establecerempíricamente el diagnóstico etiológico, la similitud clínica entre mayores y menores de 5 años y el porcentaje de coinfecciones (AU)

Introduction: Mycoplasma pneumoniae and adenovirus are two of the main causes ofpneumonia in children. The objectives of the study are to describe the epidemiological, clinical, radiological and laboratory characteristics of the cases of pneumonia caused by these microorganismsin children younger than 15 years in a Hospital of Barcelona. And also to knowif there are differences between both etiologies, between children with different ages and toknow the cases of coinfections. Methods: retrospective study of review of clinical histories of children under 15 who were visited from 2000 to 2007 in the hospital and whose IgM against M. pneumonia and/oradenovirus or the immunofluorescence or culture for adenovirus had been positive. A statisticalstudy with the program SPSS was performed. Results: seventy-three pneumonias caused by M. pneumoniae and 80 by adenovirus werediagnosed. Thirty-five were girls and 28 boys. The mean age was 5.7 and 3.5 years respectively;46.6% were younger than 5 years in M. pneumoniae and 71.3% in adenovirus infections.There was no clear stational prevalence. The most frequent clinical manifestationswere fever and cough, with good general aspect. The auscultatory findings were pathological in 141 cases, being crepitations and unilateral affectation the most frequent features. Chestx-rays showed predominantly unilateral affectation. Blood tests did not show significative alterations.There were 23 coinfections found with both microorganism and 22 with others.Conclusions: M. pneumoniae and adenovirus should be considered causal agents of paediatricpneumonias. Is remarkable the difficulty in the differential diagnosis with other pneumonias,the clinical similitude between younger and older than 5 years and the importantpercentage of coinfections (AU)