Sublingual immunotherapy in the treatment of allergic asthma: a systematic review with meta-analysis

Introduction: The guidelines for the management of allergic respiratory diseases oriented towards control from medical treatment combined with measures of environmental hygiene. Immunotherapy is one of several types of treatment, applied in combination with prophylactic drugs and environmental care. The aim of the study is to evaluate the efficacy of sublingual immunotherapy (SLIT) for house dust mites (HDM) in people with allergic asthma. Methods: The study is based on a systematic review with meta-analysis of randomized clinical trials, associating sublingual immunotherapy with the treatment of allergic patients with HDM. Results: The searches were applied in PubMed, ScienceDirect and Scielo databases. Initially, 98 articles were recovered, of which only nine were eligible. Of these, eight (88.9%) were conducted in Europe and only one (11.1%) in Asia. Comparing the outcomes expiratory volume in the first minute (FEV1 ) and sensitivity to allergens (HDM) between SLIT and placebo groups before and after intervention, no differences were observed between the groups. Conclusions: SLIT is not evidenced significantly by meta-analysis for the treatment of allergic asthma (AU)

Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode / Sensibilização por via subcutânea é superior à intraperitoneal na indução de asma por ácaro em modelo murino

ABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

RESUMO Objetivo Desenvolver um novo modelo experimental de doença pulmonar alérgica crônica por ácaro, com proeminente produção de imunoglobulina E (IgE) específica, infiltrado inflamatório eosinofílico nas vias aéreas e remodelamento, comparando duas vias diferentes de sensibilização. Métodos O protocolo teve duração de 30 dias. Camundongos BALB/c foram divididos em seis grupos submetidos à sensibilização por via subcutânea ou intraperitoneal com solução salina (controles negativos),Dermatophagoides pteronyssinus (Der p) 50 ou 500mcg, em três aplicações. Posteriormente, foram submetidos à provocação intranasal com Der p ou salina por 7 dias e sacrificados 24 horas após o último desafio. Avaliamos a titulação de IgE específica anti-Der p, densidade eosinofílica no espaço peribroncovascular e remodelamento das vias aéreas. Resultados Tanto os animais sensibilizados por via subcutânea como intraperitoneal produziram IgE específica anti-Der p. Ocorreu aumento da eosinofilia peribroncovascular apenas nos animais que receberam menor dose de Der p. Porém apenas o grupo sensibilizado com Der p 50mcg subcutânea apresentou remodelamento significativo das vias aéreas. Conclusão Neste modelo murino de asma, as duas vias de sensibilização levaram à produção de IgE específica e eosinofilia nas vias aéreas. No entanto, apenas a via subcutânea foi capaz de induzir ao remodelamento. Além disso, doses menores de Der p utilizadas foram superiores às mais elevadas, sugerindo tolerância. Mais estudos são necessários para avaliar a eficácia deste modelo no desenvolvimento da hiperresponsividade brônquica, mas ele pode ser replicado em experimentos para criação de novas estratégias terapêuticas medicamentosas ou imunoterápicas.

Use of digital media for the education of health professionals in the treatment of childhood asthma / Uso de mídia digital na educação de profissionais de saúde para tratamento da asma infantil

OBJECTIVES: Inhalation therapy is the main treatment for asthma and its adequate use has been a factor responsible for disease control; therefore, the aim of the study was to determine whether a digital media tool, which features portability on mobile phones, modifies the assimilation of the inhalation technique. METHODS: A total of 66 professionals working in the health care area with the pediatric population were selected. They were submitted to a pre-test on their knowledge of inhalation therapy. The professionals were randomized into two groups (A and B). Group A received a media application on their mobile phones showing the steps of inhalation therapy, while group B received the same information in written form only. A post-test was applied after 15 days. The results (pre- and post-) were analyzed by two pediatric pulmonologists. RESULTS: Of the 66 professionals, 87.9% were females. Of a total possible score of ten, the mean score obtained in the pre-test was 5.3 ± 3, and in the second test, 7.5 ± 2 (p < 0.000). There were no significant differences when comparing the two groups (p = 0.726). The nurses had the lowest mean scores in the initial test (2.3 ± 2); however, they were the group that learned the most with the intervention, showing similar means to those of other groups in the second test (6.1 ± 3). CONCLUSION: There was significant improvement in knowledge about inhalation therapy in all professional categories using both methods, demonstrating that education, when available to professionals, positively modifies medical practice. .

OBJETIVOS: A inaloterapia representa a principal forma de tratamento da asma e seu uso adequado tem sido fator responsável pelo controle da doença. Desse modo, o objetivo do estudo foi determinar se uma ferramenta de mídia digital, dotada de portabilidade na forma de telefonia móvel, modifica a assimilação da técnica inalatória. MÉTODOS: Foram selecionados 66 profissionais que atuam na área da saúde com população pediátrica e submetidos a um pré-teste sobre seus conhecimentos de inaloterapia. Os profissionais foram randomizados em dois grupos (A e B). O grupo A recebeu em seu telefone móvel um aplicativo de mídia com os passos da inaloterapia, enquanto o grupo B recebeu as mesmas informações apenas de forma escrita. Após 15 dias, fez-se um pós-teste. Os resultados (pré e pós) foram analisados por dois pneumologistas pediátricos. RESULTADOS: Dos 66 profissionais, 87,9% eram do sexo feminino. Num escore total possível de 10, a média das notas obtidas no pré-teste foi de 5,3 ± 3 e as do segundo teste 7,5 ± 2 (p < 0,000). Não houve diferenças significativas na comparação os dois grupos (p = 0,726). Os profissionais de enfermagem apresentaram a menor média nas provas iniciais (2,3 ± 2), porém foi o grupo que aprendeu mais com a intervenção e apresentou média similar aos outros grupos na segunda prova (6,1 ± 3). CONCLUSÃO: Houve melhoria significativa no conhecimento sobre inaloterapia em todas as categorias profissionais com o uso de ambos os métodos. Isso comprovou que a educação, quando oferecida aos profissionais, modifica positivamente a prática médica. .

A new occlusive patch test system comparable to IQ and Finn chambers.

Background: A good patch test system should have good adhesion and contact, and minimal leakage; Finn and IQ patch test system have these properties but are expensive. Aims: To develop a new cost‑effective occlusive patch test system that had good contact with the skin and was non‑irritant. Methods: The system (designated Chamber X) was fabricated using a semi‑permeable tape and a flexible virgin plastic chamber. Chamber X was developed by (i) selecting adhesive tape based on its non irritancy and adhesive potential (ii) testing plastic chamber material for its skin irritancy (iii) testing the assembled system against Finn, IQ and locally available chambers for irritancy, contact, leakage and occlusivity. Results: Chamber X showed better occlusion than IQ, Finn and locally available chambers and was comparable to, (P > 0.05) IQ and Finn in terms of irritancy, contact and leakage. Conclusions: The results demonstrate that the Chamber X offers a cost effective patch test system comparable to IQ and Finn chambers in terms of safety, adhesion, leakage and occlusivity.

Treatment of Severe Atopic Dermatitis with a Combination of Subcutaneous Allergen Immunotherapy and Cyclosporin

PURPOSE: The clinical efficacy of subcutaneous allergen immunotherapy (SCIT) for the treatment of patients with severe atopic dermatitis (AD) using house dust mite (HDM) extract has been reported. Cyclosporin has been regarded as an effective medication for treatment of severe AD. In this study, we investigated a clinical usefulness of combined treatment with SCIT and cyclosporin in patients with severe AD. MATERIALS AND METHODS: Nine patients with severe AD and hypersensitivity to HDM were treated with a combination of SCIT using HDM extract and cyclosporin for 12 months. The primary efficacy outcome was the change in the standardized clinical severity scoring system for AD (SCORAD) values, measured at 6 and 12 months, in comparison with the values at baseline. Daily dose of cyclosporin was decreased or discontinued according to the degrees of clinical improvements in individual patients. RESULTS: In 8 patients who completed 12 months of treatment, the SCORAD values significantly decreased from 71.5+/-15.5 (mean+/-SD) at baseline to 20.4+/-14.6 at 6 months and 26.3+/-13.6 at 12 months (Wilcoxon signed-rank test, p=0.01), and no significant systemic side effects were observed. Cyclosporin was discontinued in 4 of 8 patients within 8 months after starting the combined treatment. CONCLUSION: In this study, combined treatment with SCIT and cyclosporin resulted in significant clinical improvements in patients with severe AD. Further studies are needed to test the clinical usefulness of this combined treatment for patients with severe AD.

Humoral and cellular immune responses to Blomia tropicalis and concanavalin A-binding fractions in atopic patients

Blomia tropicalis, Dermatophagoides pteronyssinus and D. farinae are prevalent house dust mites. Concanavalin A-binding components derived from B. tropicalis (Bt-ConA extract) are highly immunogenic in allergic diseases. The aim of the present study was to evaluate the humoral and cellular immune responses to B. tropicalis in mite-sensitized patients. A total of 137 patients with allergic rhinitis with/without asthma and 109 non-atopic subjects were selected and analyzed by the skin prick test, and for total serum IgE and specific IgE levels to both Bt-total and Bt-ConA extracts, their proliferative response and cytokine (IFN-ã and IL-5) production by peripheral blood mononuclear cells (PBMC) stimulated with both extracts. Skin prick test showed that 70 percent of the patients were sensitized to Bt (Bt+) and similar levels of specific IgE to Bt-total and Bt-ConA extracts were demonstrable in Bt+ patients. Significant PBMC proliferation was observed in response to Bt-total extract in Bt+, but not in Bt- patients and non-atopic subjects (P < 0.001). Bt-ConA extract induced increased proliferative responses in all patient groups compared to medium alone (P < 0.05), but these responses were significantly decreased in the presence of the mannopyranoside ConA inhibitor (P < 0.05). Significant IFN-ã production was observed after Bt-ConA stimulation of Bt+ patients (P < 0.05), while Bt-total extract had no effect. IL-5 production was consistently detected in Bt+ patients after allergen-specific stimulation or with no stimulus, indicating that PBMC from allergic patients are prone to produce Th2 profile cytokines, spontaneously or inductively by allergen restimulation. These data showed that ConA-binding components isolated from B. tropicalis may contain relevant antigens that are involved in both humoral and cellular immune responses. However, without an additional purification procedure to eliminate the residual contamination with...

The expression and significance of IgE in anaphylactic shock guinea-pigs / 法医学杂志

OBJECTIVE@#To seek the pathomorphological targets for forensic expertise in anaphylactic shock.@*METHODS@#The expression of IgE in hearts, lungs, livers, spleens, kidneys, gastrics, intestinals, tracheas and tonsils of anaphylactic shock guinea-pigs was observed at 0, 6, 12 h and 24 h respectively by tissue chip S-P immuno-histochemical method.@*RESULTS@#Positive expression of IgE presented in lungs and tracheas in the test group with the peak at 0 hour and it declined as time advanced, and also there were significant differences at different times (P<0.05).@*CONCLUSION@#The immuno-histochemical method of detecting the expression of IgE in lungs, tracheas and spleens can be supposed to be the pathomorphological targets for forensic expertise in anaphylactic shock. The weakening of the positive expression of IgE in lungs and tracheas as the time advanced suggested that in this kind of case the autopsy should be arried out as early as possible.

Ensayo clínico diagnóstico con extracto alergénico de Blomia tropicalis en adultos alérgicos y voluntarios sanos / Test clinic-diagnostic with allergenic extract of Blomia tropicalis in adults allergics and healthy adults

Antecedentes: en Cuba no existen antecedentes de estudios realizados para demostrar la eficacia de una prueba diagnóstica de alergia a Blomia tropicalis a pesar de ser uno de los principales ácaros responsables de esta enfermedad humana que sólo en Cuba afecta a más de 2, 200, 000 personas. Objetivos: evaluar el extracto alergénico Blomia tropicalis producido en el Centro Nacional de Biopreparados (BioCen), en la prueba de punción cutánea como diagnóstico de alergia a este alergeno existente en todos los países tropicales y subtropicales. Material y método: se seleccionaron 50 pacientes con historia clínica positiva de alergia al polvo casero y 50 personas sanas. A todos se le realizó la prueba por punción cutánea en duplicado, con dos diluciones del extracto (20 000 UB/mL y 2 000 UB/mL) y controles positivos y negativos. Se midió el diámetro medio del habón y el diámetro ortogonal y se calculó la media. Se calculó la media del tamaño del habón de los duplicados, lo que constituyó el tamaño de la reacción. La validez de la prueba se estimó calculando la sensibilidad y especificidad. Para ello se utilizó el programa EPITABLE. Resultados: la prueba cutánea fue positiva en 78 por ciento de los enfermos y en 6 por ciento de los sanos, para una sensibilidad de 78 por ciento, intervalo de confianza (IC) 63.7 - 88.0 y una especificidad de 94 por ciento, IC 82.5 - 98.4. El valor predictivo positivo fue de 92.9 por ciento, IC 79.4 - 98.1 y el valor predictivo negativo de 81 por ciento, IC 68.2 - 89.7. Conclusiones: el extracto alergénico de Blomia tropicalis producido en BioCen es eficaz como prueba para el diagnóstico.

Procedimiento para realizar pruebas broncodinámicas con alergenos inhalados / Proccedings to bronchodynamics tests with inhalated allergens

El asma es una de las enfermedades crónicas más frecuentes de los niños. Se caracteriza por hiperreactividad de las vías aéreas a estímulos inespecíficos (metacolina e histamina) y específicos (alergenos). Las pruebas broncodinámicas determinan la broncolabilidad del niño asmático y ayudan a establecer el diagnóstico funcional. Deben realizarse con extractos antigénicos de alta calidad, acuosos liofilizados y estandarizados; se puede utilizar un circuito abierto o cerrado y un dosímetro, la dosis inicial del alergeno es más baja que con la que se obtuvo la reactividad cutánea positiva, realizando incrementos sucesivos hasta que el VEF-1 descienda 15 por ciento o más. La seguridad del paciente es fundamental, por eso las pruebas debe realizarlas personal especialmente adiestrado.

Rinitis y pólipos nasales: su relación con ácaros domésticos / Nasal polyps and rhinitis: relationship with domestic acarus

Antecedentes: en las personas mayores de un año las alergias respiratorias pueden estudiarse desde el punto de vista etiológico utilizando para ello las pruebas cutáneas con alergenos específicos. Material y método: a 76 pacientes con diagnóstico de rinitis alérgica y pólipos nasales que envió el servicio de Otorrinolaringología al de Alergia de Esmeralda Camagüey, se les realizó un estudio para valorar la reactividad cutánea a los ácaros Dermatophagoides pteronyssinus, Dermatophagoides siboney y Blomia tropicalis. A cada paciente se le hizo la prueba por punción cutánea en duplicado. A los 15 minutos se dibujaron los contornos de los habones y se midieron el diámetro mayor y el ortogonal de cada uno y se calculó la media. Igual se hizo con los habones de los duplicados. Se consideraron positivos cuando el diámetro medio del habón fue > 3 mm y negativo < 3 mm. Resultados: en los pacientes con rinitis la mayor frecuencia de positivos correspondió a Dermatophagoides pteronyssinus y la mayor frecuencia de negativos a Dermatophagoides siboney. En los pacientes con pólipos nasales hubo un predominio (p < 0.05) de positivos a Dermatophagoides pteronyssinus y hubo un predominio (p < 0.05) de negativos a Dermatophagoides siboney. Conclusiones: el ácaro Dermatophagoides pteronyssinus provocó más reacciones positivas que Dermatophagoides siboney y Blomia tropicalis en pacientes con rinitis alérgica y en pólipos nasales.

Liposome entrapped allergen reduces plasma histamine in sensitized mice.

Immunotherapy of allergic diseases is associated with problems of adverse systemic reactions. We have shown earlier that liposome entrapped allergen (LEA) is effective in inducing IgG response and restricting IgE response in immunized mice. This mode of treatment may be more effective and safer if it can prevent anaphylaxis. To determine this feature, mice were administered allergen preparations repeatedly and later challenged with the same allergen. Mice given liposomal preparation showed lower specific IgE response as compared to the mice given free allergen or alum adsorbed allergen of Artemisia scoparia. Specific IgG response was higher in mice immunized with LEA. The mice immunized with liposomal preparation survived whereas others injected with free allergen or alum adsorbed allergen died probably due to anaphylaxis. High levels of histamine were observed in mice injected with free allergen as compared to the mice injected LEA. The increase in plasma histamine level may be the cause of anaphylaxis during allergen challenge. In conclusion, LEA could be used as a safe and effective mode of immunotherapy for allergy diseases, since it reduces plasma histamine levels considerably thereby reducing the chances of anaphylaxis.

Multiple dust allergy in a semiurban environs.

Multiple dust allergy in a study of 100 patients of nasobronchial hypersensitivity has been demonstrated by skin testing in Chandigarh and successfully desensitised over a 3-year period. The results are discussed and the multiple factors involved postulated.

Comportamiento de la reactividad cutánea y los valores de IgE total e IgE alergeno específico en niños con un año inmunoterapia supervisada / Behavior of the cutaneous reaction and total IgE and IgE specific values in children with a year of supervised inmunotherapy

Se estudiaron 30 niños con diagnóstico de asma bronquial alérgica al Dermatofagoides, con edades en un rango de 35 a 14 años. Se cuantificó el tamaño de la pápula y eritema de la prueba cutánea así como los niveles de IgE total y específica al inicio de la inmunoterapia específica con antígenos acuosos peso/volumen y se les monitorizaron ambos parámetros a los 6 meses de tratamiento. Las dimensiones para la pápula disminuyeron en 45.7 porciento para el D. farinae un 48.1 porciento de igual manera el eritema disminuyó un 25 porciento para el D. pteronyssinus y un 17.27 porciento para el D. farinae, al cabo de un año de inmunoterapia. Los niveles séricos totales de IgE promedio e iniciales fueron 696.23 +- 711.35 UI, disminuyeron un 27.73 por ciento a los 6 meses y al finalizar los 12 meses las cifras séricas fueron de 162.23+-75.25UI, con un decremento respecto al inicio de un 55.79 por ciento (p<0.0001). La IgE específica también se modificó luego de 1 año de tratamiento y para los niños sensibles al Dermatofagoides pteronyssinus 22/30 cambiaron su clase de Rast a una menor (73.33 por ciento) mientras que para el D. farinae 18/26 cambiaron a una clase menor de Rast(16.23 por ciento).

Pruebas cutáneas en alergia / Allergen skin testing

Las pruebas cutáneas son uno de los principales métodos in vivo para evaluar la presencia de IgE específica contra algún alergeno. En este artículo se hace una revisión actualizada de las técnicas de aplicación, radiactivos utilizados, evaluación y ausencia de efectos secundarios de las pruebas cutáneas para ayudar al alergólogo a su mejor apliación clínica

Aeroalargenos y alergia respiratoria en el estado de Oaxaca, México / Aeroallergens and respiratory allergy in the state of Oaxaca, Mexico

Se estudiaron 108 pacientes del estado de Oaxaca, M[exico., 75 hombres, 62 mujeres, con promedio de edad de 29 a;os, con diagnosticos de asma, rinitis y sinusitis, para determinar la frecuencia de aeroalargenos comprometidos. Se efectuaron pruebas de escarificacion con alergenos glicerinados 1:20 p/v Hollister S. Los resultados muestran al Dermaphagoides como principal alergeno, seguido de polvo casero y los polenes de capriola y lolium.