Real-world study: drug reduction in children with allergic rhinitis and asthma receiving immunotherapy.

Background: The reduction of pharmacological treatment after allergen immunotherapy (AIT) for house dust mites (HDMs) has been little studied in children. Objective: To evaluate the reduction of pharmacological treatment comparing children that receive HDM immunotherapy (AIT group) versus only pharmacotherapy. Methods: A historic cohort of children with rhinitis or asthma was assessed. The main outcome was the frequency of complete drug discontinuation. Results: 100% drug reduction was higher for rhinitis (4-year cumulative incidence: 30 vs 10.7%) and asthma (24.1 vs 10.5%) in the AIT group (n = 987) than in the pharmacotherapy group (n = 2012). Conclusion: Immunotherapy is associated with a significant reduction of pharmacotherapy in children. This is a marker of clinical control and could be associated with positive economic impact.

The benefits of allergen immunotherapy for house dust mites has been little studied in children. The usefulness of this treatment in asthma over the use of pharmacotherapy has also not been clearly evaluated. The use of immunotherapy allowed greater reductions in pharmacological treatment in children with rhinitis and asthma. Immunotherapy is a useful treatment for childhood rhinitis and asthma and reduces the risk of adverse effects from pharmacological treatments.

Recombinant T-cell epitope conjugation: A new approach for Dermatophagoides hypoallergen design.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. METHODS: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. RESULTS: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL- 2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. CONCLUSIONS: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.

Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. OBJECTIVE: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. RESULTS: A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. CONCLUSIONS: Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.

An Engineered Hybrid Protein from Dermatophagoides pteronyssinus Allergens Shows Hypoallergenicity.

The house dust mite (HDM) Dermatophagoides pteronyssinus is an important risk factor for asthma and rhinitis. Allergen specific immunotherapy that is based on recombinant proteins has been proposed for the safer and more efficient treatment of allergic diseases. The aim of this study was to design and obtain a hybrid protein (DPx4) containing antigenic regions of allergens Der p 1, Der p 2, Der p 7, and Der p 10 from this mite. DPx4 was produced in Escherichia coli and its folding was determined by circular dichroism. Non-denaturing dot-blot, ELISA, basophil activation test, dot blot with monoclonal antibodies, ELISA inhibition, and cysteine protease activity assays were performed. Mice that were immunized with DPx4 were also analyzed. We found that DPx4 had no cysteine protease activity and it showed significantly lower IgE reactivity than Der p 1, Der p 2, and D. pteronyssinus extract. DPx4 induced lower basophil activation than Der p 2 and the allergen extract. Immunized mice produced IgG antibodies that inhibited the binding of allergic patient's IgE to the allergen extract and induced comparatively higher levels of IL-10 than the extract in peripheral blood mononuclear cells (PBMC) culture. These results suggest that DPx4 has immunological properties that are useful for the development of a mite allergy vaccine.

[Safety of subcutaneous immunotherapy with tyrosine-adsorbed house dust mite extracts in patients with allergic disease]. / Seguridad de la inmunoterapia subcutánea con extractos tirosinados de ácaros de polvo doméstico en pacientes con enfermedad alérgica.

BACKGROUND: In spite of allergen-specific immunotherapy (SIT) multiple benefits, its use is restricted in some countries owing to concerns about severe adverse reactions. OBJECTIVE: To evaluate systemic adverse reactions in patients with atopic dermatitis, allergic asthma, allergic rhinitis and allergic conjunctivitis who received subcutaneous immunotherapy with tyrosine-adsorbed Dermatophagoides and Glycyphagoides dust mites extracts. METHODS: Retrospective study of the 2010-2015-period that included 773 patients diagnosed with IgE-mediated diseases, where the safety of allergen-specific immunotherapy was described according to the World Organization of Allergy subcutaneous immunotherapy-induced systemic reactions classification system. RESULTS: 79.7 % of patients had rhinitis, 54.9 % asthma, 34.5 % conjunctivitis and 16.4 % atopic dermatitis. Out of 12,546 tyrosine-adsorbed extract doses, 45 systemic reactions were recorded: 12 were grade 1 (30 %), 27 grade 2 (67.5 %) and 1 was grade 3 (2.5 %); the reaction rate was 0.35 per 100 administered injections, for an incidence rate of 5.8 %. No fatal reactions occurred. CONCLUSION: The frequency of systemic reactions with subcutaneous immunotherapy with Dermatophagoides farinae, Dermatophagoides pteronyssinus and Blomia tropicalis tyrosine-adsorbed extracts was similar to that reported with other extracts.

Antecedentes: Pese a los múltiples beneficios de la inmunoterapia alérgeno-específica, en algunos países se restringe su uso por temor a las reacciones adversas severas. Objetivo: Evaluar las reacciones sistémicas adversas en pacientes con dermatitis atópica, asma, rinitis y conjuntivitis alérgicas, que recibieron inmunoterapia subcutánea con extractos tirosinados para ácaros Dermatophagoides y Glycyphagoides. Métodos: Estudio retrospectivo del periodo 2010-2015 en el que se incluyó a 773 pacientes con diagnóstico de enfermedades mediadas por IgE. Se describió la seguridad de la inmunoterapia alérgeno-específica conforme al sistema de clasificación de las reacciones sistémicas con inmunoterapias subcutánea de la Organización Mundial de Alergias. Resultados: 79.7 % de los pacientes presentó rinitis, 54.9 % asma, 34.5 % conjuntivitis y 16.4 % dermatitis atópica. De 12 546 dosis subcutánea con extractos tirosinados se registraron 45 reacciones sistémicas: 12 grado 1 (30 %), 27 de grado 2 (67.5 %) y 1 grado 3 (2.5 %); la tasa de reacción fue de 0.35 por cada 100 inyecciones administradas, que representó una incidencia de 5.8 %. No se registraron reacciones fatales. Conclusión: Con la inmunoterapia subcutánea con extractos tirosinados de Dermatophagoides farinae, Dermatophagoides pteronyssinus y Blomia tropicalis se presentó una frecuencia de reacciones sistémicas similar a la informada con otros extractos.

[The impact of subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus on the quality of life of patients with allergic rhinitis and asthma]. / Impacto de la inmunoterapia subcutánea con Dermatophagoides farinae y Dermatophagoides pteronyssinus sobre la calidad de vida de pacientes con rinitis y asma alérgica.

INTRODUCTION: The prevalence of asthma and allergic rhinitis in Colombia is increasing at the same rate as it is in other parts of the world. It has been determined that allergen-specific subcutaneous immunotherapy is effective in subjects with allergic rhinitis and asthma that are sensitized to house dust mites: Dermatophagoides farinae and Dermatophagoides pteronyssinus . OBJECTIVE: To provide evidence on changes in the quality of life of subjects induced by allergen-specific subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus . MATERIALS AND METHODS: We selected 76 subjects with a diagnosis of respiratory allergy with sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus . The instruments used for evaluating the quality of life were Kidscreen-27 and SF-36. These instruments were applied twice for each subject: once during the first visit, and during the twelfth visit corresponding to the one-year follow-up. RESULTS: Twenty-two subjects completed this study. After one year of treatment with allergen-specific subcutaneous immunotherapy, we found positive changes in terms of the quality of life. In children, the main change was in the School Environment domain while in adults it was in the Physical Function domain. CONCLUSION: We evaluated, for the first time in Colombia, benefits induced by allergen-specific subcutaneous immunotherapy for dust mites in terms of quality of life in subjects with allergic rhinitis and asthma. These results demonstrated that allergen-specific subcutaneous immunotherapy produces a positive influence on subjects sensitized to dust mites that received allergen-specific subcutaneous immunotherapy to Dermatophagoides farinae and Dermatophagoides pteronyssinus after one year.

Impacto de la inmunoterapia subcutánea con Dermatophagoides farinae y Dermatophagoides pteronyssinus sobre la calidad de vida de pacientes con rinitis y asma alérgica / The impact of subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus on the quality of life of patients with allergic rhinitis and asthma

Introducción. Como sucede en otras partes del mundo, la prevalencia de asma y rinitis alérgica en Colombia está en aumento. Se ha establecido que la inmunoterapia subcutánea con alérgenos es eficaz a largo plazo en pacientes con rinitis alérgica y asma sensibilizados a Dermophagoides. Objetivo. Proveer evidencia sobre los cambios relacionados con la calidad de vida inducidos por la inmunoterapia subcutánea en sujetos con alergia respiratoria. Materiales y métodos. Se seleccionaron 76 sujetos con diagnóstico de alergia respiratoria con sensibilización a Dermatophagoides farinae y Dermatophagoides pteronyssinus . Para la evaluación de la calidad de vida se emplearon los instrumentos Kidscreen-27 y SF-36 ( Short form 36 ). Estos instrumentos se aplicaron en dos ocasiones: durante la primera visita, en la cual se iniciaba la inmunoterapia subcutánea, y un año después de haberse iniciado el tratamiento. Resultados. Al año de estar recibiendo la inmunoterapia, los 22 sujetos que completaron el estudio presentaron cambios positivos en términos de calidad de vida. En los niños, el principal cambio se presentó en el dominio del ´entorno escolar´ mientras que en los adultos fue en el de la ´función física´ . Discusión. Se evaluaron por primera vez en Colombia los beneficios inducidos por la inmunoterapia subcutánea para ácaros de polvo en la calidad de vida de sujetos con rinitis alérgica y asma mediante los cuestionarios Kidscreen-27 y SF-36. Los resultados proveen evidencia de que la inmunoterapia subcutánea influye positivamente en la calidad de vida en sujetos con rinitis asmática y asma sensibilizados a los ácaros de polvo.

Introduction: The prevalence of asthma and allergic rhinitis in Colombia is increasing at the same rate as it is in other parts of the world. It has been determined that allergen-specific subcutaneous immunotherapy is effective in subjects with allergic rhinitis and asthma that are sensitized to house dust mites: Dermatophagoides farinae and Dermatophagoides pteronyssinus . Objective: To provide evidence on changes in the quality of life of subjects induced by allergen-specific subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus . Materials and methods: We selected 76 subjects with a diagnosis of respiratory allergy with sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus . The instruments used for evaluating the quality of life were Kidscreen-27 and SF-36. These instruments were applied twice for each subject: once during the first visit, and during the twelfth visit corresponding to the one-year follow-up. Results: Twenty-two subjects completed this study. After one year of treatment with allergen-specific subcutaneous immunotherapy, we found positive changes in terms of the quality of life. In children, the main change was in the School Environment domain while in adults it was in the Physical Function domain. Conclusion: We evaluated, for the first time in Colombia, benefits induced by allergen-specific subcutaneous immunotherapy for dust mites in terms of quality of life in subjects with allergic rhinitis and asthma. These results demonstrated that allergen-specific subcutaneous immunotherapy produces a positive influence on subjects sensitized to dust mites that received allergen-specific subcutaneous immunotherapy to Dermatophagoides farinae and Dermatophagoides pteronyssinus after one year.

Sublingual immunotherapy in children: complete and updated review supporting evidence of effect.

PURPOSE OF REVIEW: The interest in sublingual immunotherapy (SLIT) is still growing worldwide and especially for the pediatric age group, this modality is appealing. Lately, some negative systematic review articles have been published on SLIT in children. However, high quality articles published from 2007 onward had not been included. RECENT FINDINGS: Explanations are sought for the negative outcomes in these reviews and shortcomings are discussed. New pediatric studies - not included in the previous reviews -designed taking into account the golden rules for SLIT (high daily dose, starting at least 4 months before pollen season) do show statistically significant improvement in symptom and medication scores for rhinitis and asthma in pollen allergy. New house dust mite studies still show inconsistent data. SUMMARY: Evidence of effect is confirmed for SLIT in children with allergic rhinitis or asthma caused by pollen exposure. For house dust mite asthma, evidence is still nonconcordant. New techniques to improve SLIT efficacy are under investigation.

[Sublingual immunotherapy in allergic rhinitis and asthma in 2-5 year-old children sensitized to mites]. / Inmunoterapia sublingual en rinitis alérgica y asma en niños de dos a cinco años sensibilizados con ácaros.

BACKGROUND: More than 10 years ago prick tests have been applied to children from the age of 12 months and a lot of them were given sublingual immunotherapy with significant acceptance from family and without undesirable reactions. OBJECTIVE: To assess the efficacy and safety of sublingual immunotherapy in children. PATIENTS AND METHODS: A clinical trial was done in 138 children with asthma or rhinitis and positive prick test to Dermatophagoides pteronyssinus, D. siboney and Blomia tropicalis. Randomly 69 received sublingual immunotherapy, applying two drops in growing concentrations of 500, 1,000, 2,000, 10,000 and 20,000 biological units. The concentration of 20,000 was left as maintenance till completes the scheme. RESULTS: Out of the 138 children included in the study 69, who received sublingual immunotherapy, showed a difference in variables in relation to control group, and the attendance to emergency services was lower in the study group than in the control one for a relative risk of 0.39 with a 95% confidence interval of 0.19, 0.81. Corticosteroid consumption was lower in patients treated for a relative risk of 0.37 and 95% confidence interval of 0.14, 0.79. Out of the 69 patients, 11 had mild (8.6%) and moderate (7.2%) adverse reactions. CONCLUSIONS: 84% did not have any reaction, thus, sublingual immunotherapy with allergenic extracts of acarus is effective and safe in the treatment of asthma and allergic rhinitis.

Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy.

BACKGROUND: Several studies have demonstrated the efficacy and safety of sublingual immunotherapy in the treatment of respiratory allergy. OBJECTIVE: To determine the frequency of systemic adverse reactions in patients treated with standardized extracts of sublingual immunotherapy. METHODS: Allergic patients with rhinitis with or without asthma and sensitized to at least 1 allergen were included. Increasing doses of standardized allergens were administered until reaching an average dose accumulated of 7,200 U after 26 weeks of treatment. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology immunotherapy position paper. RESULTS: Forty-three patients with a median age of 11 years (interquartile range, 8-20 years) were included. All the patients had allergic rhinitis, and 63% had asthma; they were sensitized mostly to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Four patients (9%) presented with an immediate and 1 (2%) with a late systemic reaction. In total, 7 systemic reactions occurred in 23,154 doses, and all were associated with wheezing or worsening of nasal symptoms (grade 2); in addition, 1 patient had angioedema and urticaria (grade 3). CONCLUSIONS: In this group, systemic reaction frequency was 11.6%, and all were classified as grade 2 or 3. Further assessments in larger samples of patients are required in the context of randomized controlled trials.

Mite-specific immunotherapy using allergen and/or bacterial extracts in atopic patients in Brazil.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and antibody response changes after specific immunotherapy (SIT) using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial extracts in Brazilian mite-atopic patients. METHODS: One-hundred patients with allergic rhinitis were selected for a randomized double-blind, placebo-controlled trial and distributed into 4 groups: Dpt (Dpt allergen extract), Dpt+MRB (Dpt allergen plus mixed respiratory bacterial extracts), MRB (MRB extract only) and placebo. Rhinitis symptom and medication scores; skin prick test (SPT) to Dpt extract; and serum immunoglobulin (Ig) E, IgG4, and IgG1 levels to Dpt, Der p 1, and Der p 2 allergens were evaluated before and after a year of treatment. RESULTS: After 1 year, the SPT response was reduced in the Dpt group (P=.03), whereas IgE levels to Der p 2 decreased only in the Dpt (P = .048) and Dpt+MRB (P = .005) groups. IgG4 and IgG1 levels to Dpt and Der p 1 increased in the Dpt group (P < .05), whereas in the Dpt + MRB group the IgG1 level only increased to Dpt (P=.001) and the IgG4 only increased to Der p 1 (P=.049). IgE levels to Dpt decreased only in the MRB (P= .005) and Dpt + MRB (P= .001) groups. Rhinitis symptom and medication scores fell in all groups, including the placebo group (P<.001). CONCLUSIONS: SIT using Dpt extract alone was effective in reducing SPT response and IgE levels to Der p 2 allergen, while bacterial extracts induced decreases in IgE levels to whole Dpt extract. However, only groups receiving Dpt allergen had higher levels of IgG1 and IgG4 to Dpt and Der p 1 after a year of treatment.

[Sublingual immunotherapy with allergenic extract of Dermatophagoides pteronyssinus in asthmatic children]. / Inmunoterapia sublingual con extracto alergénico de Dermatophagoides pteronyssinus en niños con asma.

BACKGROUND: Sublingual immunotherapy is based on the treatment of distinct pathologies. It is not exempt from discomfort and hazards; thus, alternative approaches for therapy are being tested. OBJECTIVE: To assess the effectiveness of sublingual immunotherapy, with Dermatophagoides pteronyssinus in asthmatic children. MATERIAL AND METHODS: Fifty pediatric patients of both sexes between 5 and 15 years were randomly divided into two groups. The first group received sublingual immunotherapy with Dermatophagoides pteronyssinus in concentrations of 500, 1000, 2000, 5000, 8000 and 10,000 biological units. Both groups received conventional therapy, and spirometry and total IgE were measured every 30 days. The use of bronchodilators and steroids was assessed before and during the test. RESULTS: Peak expiratory flow improved in the study group with a remarkable difference (p < 0.05). There were not significant differences in the control group (p > 0.05); however, at the end of the study an increase of 80% was observed. In urgency services, patients who received immunotherapy had relative risk (RR) = 0.36 and confidence interval (CI) of 95%, 0.15, 0.84. The use of steroids equally decreased in patients receiving immunotherapy RR = 0.27, CI 95%, 0.10, 0.69. CONCLUSIONS: Sublingual immunotherapy does reduce the risk for asthma episodes in children.