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INTRODUCTION: In patients suffering from allergic asthma, especially in the pediatric age-group, allergen immunotherapy (AIT) could be of benefit and has the potential of long-term disease modification. AREAS COVERED: We reviewed the evidence for a beneficial effect of AIT in allergic asthma. A correct selection of the possible candidates for AIT is crucial. We define the comprehensive allergic asthma diagnosis: confirming asthma, confirming allergic sensitization and having symptoms on exposure to the relevant allergens.We analyze why the first trials on AIT for asthma were contradictory; we consider the results of systematic reviews and discuss the high degree of heterogeneity often found in meta-analysis. We assess recent, double-blind, placebo-controlled trials in sublingual AIT that provide robust evidence for a reduction in acute asthma exacerbations and a decrease in the use of inhaled corticosteroids. Further, we demonstrate how real-world trials and large pharmacy data-based analyses confirm these findings for SLIT and SCIT. Finally, we explore the option of AIT in severe asthma patients, once well-controlled on biologic therapy. EXPERT OPINION: Clear indications for AIT in asthma guidelines would benefit allergic asthmatics. AIT is a therapeutic option in appropriately selected asthmatics. Three years treatment has the potential for long-term tolerance, with persisting benefits years after discontinuation.
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Asma , Hipersensibilidade , Criança , Humanos , Alérgenos , Asma/diagnóstico , Asma/terapia , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.
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BACKGROUND: There are different guidelines for the diagnosis of allergic diseases and the application of allergen immunotherapy (AIT). OBJECTIVE: To describe how Mexican allergists diagnose and treat respiratory and food allergies with AIT. METHODS: 227 allergists who attended an immunotherapy symposium were surveyed; the topics investigated were the daily practices in the diagnosis of respiratory and food allergies, as well as ways to apply AIT. RESULTS: The surveyed allergists use skin prick tests for the diagnosis of both respiratory and food allergies in 100 % and 87.7 % of their cases respectively; in vitro diagnosis through serum specific IgE in 55.5 % and 63 %, and molecular diagnostics in 14.1% and 13.2 %. For aeroallergens, 81 % prescribe subcutaneous AIT, 77.9 % use liquid sublingual AIT, and 1.8 % prefer SLIT in tablets; however, 45 % indicated that they would use tablets in the future. Regarding food allergens, most respondents did not prescribe AIT; however, 55% of them are interested in oral AIT and 59% of them are interested in sublingual AIT. CONCLUSIONS: Generally, the diagnosis and treatment of allergic diseases are carried out according to international guidelines; besides, the interviewed allergists expressed flexibility to adopt new schemes.
Antecedentes: Existen lineamientos para el diagnóstico de las enfermedades alérgicas y la aplicación de inmunoterapia con alérgenos (ITA). Objetivo: Describir cómo los alergólogos mexicanos diagnostican y tratan con ITA las alergias alimentaria y respiratoria. Métodos: Se encuestó a 227 alergólogos que acudieron a un simposio de inmunoterapia; se indagaron prácticas cotidianas en el diagnóstico de las alergias respiratoria y alimentaria, así como en la forma de aplicar la ITA. Resultados: Los alergólogos utilizan las pruebas cutáneas por punción para el diagnóstico de las alergias respiratorias y alimentarias en 100 y 87.7 % de los casos de una y otra; diagnóstico in vitro mediante determinación de IgE alérgeno-específica en 55.5 y 63 %; y diagnóstico molecular por componentes en 14.1 y 13.2 %. Para los aeroalérgenos, 81 % emplea ITA subcutánea; 77.9 %, ITA sublingual líquida; 1.8 %, ITA sublingual en tabletas; 45 % indicó que estaba dispuesto a emplear tabletas en el futuro. Para los alérgenos de alimentos, la mayoría no utilizaba ITA, aunque 55 % se interesa en la ITA oral y 59 %, en la ITA sublingual. Conclusiones: En términos generales, el diagnóstico y tratamiento de las enfermedades alérgicas se realizan conforme los lineamientos internacionales, además, los alergólogos encuestados mostraron flexibilidad para adoptar nuevos esquemas.
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Alérgenos/uso terapêutico , Dessensibilização Imunológica , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Padrões de Prática Médica , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/terapia , Pesquisas sobre Atenção à Saúde , Humanos , México , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Sensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. OBJECTIVE: To assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. METHODS: A double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). RESULTS: The 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26-61) of placebo values, whereas medication was 34.5% (22.4%-63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. CONCLUSIONS: Subcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).
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BACKGROUND: Specific immunotherapy is a treatment aimed at modifying the course of the allergic disease, with which important immunological and clinical changes are achieved. OBJECTIVE: To assess the effectiveness and safety of subcutaneous immunotherapy in patients diagnosed with respiratory allergies in the University Hospital of Puebla, Mexico. METHODS: A longitudinal, analytic, quasi-experimental study. The study was carried out with patients aged four to sixty-five years, diagnosed with allergic rhinitis or asthma, with sensitization to aeroallergens, in whom immunotherapy was started. For the effectiveness assessment, the Control of Allergic Rhinitis and Asthma Test (CARAT) was used. Safety was assessed through Portnoy's Questionnaire Survey of Adverse Reactions. RESULTS: 59 patients were included: 72.9% were female; 23.7% of them were diagnosed with allergic rhinitis and asthma, and 76.3% were diagnosed with allergic rhinitis. The comparison of averages of the CARAT questionnaire at the beginning of the treatment and after four months of follow up showed a statistically significant positive development. An incidence of adverse local reactions of 9.03% was found; no adverse systemic reactions were reported. CONCLUSIONS: The assessed scheme of subcutaneous immunotherapy got to significantly decrease the asthma symptoms and AR symptoms, with a desirable safety profile.
Antecedentes: La inmunoterapia específica es un tratamiento orientado a modificar el curso de la enfermedad alérgica y con la que se han logrado importantes cambios inmunológicos y clínicos. Objetivo: Evaluar eficacia y seguridad de la inmunoterapia subcutánea en pacientes con diagnóstico de alergia respiratoria en el Hospital Universitario de Puebla, México. Métodos: Estudio longitudinal, analítico, cuasiexperimental. Se incluyeron pacientes de cuatro a 65 años con diagnóstico de asma o rinitis alérgica, con sensibilización a aeroalérgenos, que iniciaron tratamiento con inmunoterapia. Para la valoración de la eficacia se utilizó el cuestionario Control of Allergic Rhinitis and Asthma Test (CARAT). La seguridad se evaluó mediante el cuestionario de reacciones adversas de Portnoy. Resultados: Se incluyeron 59 pacientes, 72.9 % fueron mujeres; 23.7 % con diagnóstico de rinitis alérgica y asma y 76.3 % con diagnóstico de rinitis alérgica. La comparación de promedios del cuestionario CARAT al inicio del tratamiento y a los cuatro meses de seguimiento mostró evolución favorable estadísticamente significativa. Se encontró una incidencia de reacciones adversas locales de 9.03 %; no se reportaron reacciones adversas sistémicas. Conclusiones: El esquema de inmunoterapia subcutánea evaluado logra disminuir significativamente los síntomas del asma y la rinitis alérgica, con un conveniente perfil de seguridad.
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Alérgenos/administração & dosagem , Dessensibilização Imunológica , Hipersensibilidade Respiratória/terapia , Administração por Inalação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In Mexico, allergen immunotherapy (AIT) and immunotherapy with hymenoptera venom (VIT) is traditionally practiced combining aspects of the European and American school. In addition, both types of extracts (European and American) are commercially available in Mexico. Moreover, for an adequate AIT/VIT a timely diagnosis is crucial. Therefore, there is a need for a widely accepted, up-to-date national immunotherapy guideline that covers diagnostic issues, indications, dosage, mechanisms, adverse effects and future expectations of AIT (GUIMIT 2019). METHOD: With nationwide groups of allergists participating, including delegates from postgraduate training-programs in Allergy/Immunology-forming, the guideline document was developed according to the ADAPTE methodology: the immunotherapy guidelines from European Academy of Allergy and Clinical Immunology, German Society for Allergology and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma, and Immunology were selected as mother guidelines, as they received the highest AGREE-II score among international guidelines available; their evidence conforms the scientific basis for this document. RESULTS: GUIMIT emanates strong or weak (suggestions) recommendations about practical issues directly related to in vivo or in vitro diagnosis of IgE mediated allergic diseases and the preparation and application of AIT/VIT and its adverse effects. GUIMIT finishes with a perspective on AIT modalities for the future. All the statements were discussed and voted on until > 80 % consensus was reached. CONCLUSIONS: A wide and diverse group of AIT/VIT experts issued transculturized, evidence-based recommendations and reached consensus that might improve and standardize AIT practice in Mexico.
Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno. Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento. Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019. Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación. Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.
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Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Imunoglobulina E , Imunoterapia/normas , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologiaRESUMO
BACKGROUND: The Latin American Society of Allergy, Asthma, and Immunology (SLAAI) presents a document about the use of immunotherapy (IT) in Latin America, where administration patterns, indications and contraindications, effects on health, adverse events and socioeconomic impact are reviewed. OBJECTIVE: To review publications analyzing the use of IT in Latin America. METHODS: A literature review was carried out in order to identify works addressing IT in Latin America. This review was focused on practical scientific information available on IT in the region, and a parallel comparison was made with practices observed in the United States and European countries. RESULTS: Of the 21 Latin American countries included, only 9 had original articles meeting the selection criteria; a total of 82 articles were selected, most of them from Brazil and Mexico. Most widely used allergenic extracts in Latin America tropical and subtropical regions were those of mites and pollen. CONCLUSION: Although it is true that there are huge challenges for the future of IT in Latin America, studies on subcutaneous IT and sublingual IT are increasing, but most of them are retrospective and some have design bias, and more prospective studies are therefore required, using internationally validated scales for clinical evaluation.
Antecedentes: La Sociedad Latinoamericana de Alergia, Asma e Inmunología (SLAAI) presenta un documento acerca del uso de la inmunoterapia en Latinoamérica en el que se revisan los patrones de administración, indicaciones y contraindicaciones, efectos sobre la salud, eventos adversos e impacto socioeconómico. Objetivo: Revisar las publicaciones que abordaron el uso de la inmunoterapia en América Latina. Métodos: Se llevó a cabo revisión de la literatura para identificar trabajos enfocados en la inmunoterapia en América Latina. Esta revisión se enfocó en la información científica práctica disponible en la región sobre la inmunoterapia y se realizó un paralelo a lo observado en Estados Unidos y países europeos. Resultados: De los 21 países latinoamericanos incluidos, solo nueve tenían artículos originales que cumplían con los criterios de selección; en total se seleccionaron 82 artículos, la mayoría de Brasil y México. Los extractos alergénicos más utilizados fueron los de ácaros y polen en las regiones tropicales y subtropicales de América Latina. Conclusión: Si bien hay grandes desafíos para el futuro de la inmunoterapia en América Latina y los estudios de inmunoterapia subcutánea e inmunoterapia sublingual están aumentando, la mayoría son retrospectivos y algunos con sesgo de diseño, por lo que se requieren más trabajos prospectivos en los que se utilicen escalas validadas internacionalmente para la evaluación clínica.
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Alérgenos/uso terapêutico , Misturas Complexas/uso terapêutico , Dessensibilização Imunológica/métodos , Hipersensibilidade/terapia , Ensaios Clínicos como Assunto , Humanos , Hipersensibilidade/imunologia , América LatinaRESUMO
BACKGROUND: Since 1988, numerous allergen immunotherapy guidelines (AIT-GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely underused. OBJECTIVE: To evaluate AIT-GLs with AGREE-II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. METHODS: Allergist, from different continents, knowledgeable in AIT and AGREE-II trained were selected into the project team. The project received methodologists' guidance. AIT-GLs in any language were sought from 1980 to 2016; AIT-GLs were AGREE II-evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists' consulting. RESULTS: We found 31 AIT-GLs (15 post-2010), ranging from local consensus reports to international position papers (EAACI, AAAAI-ACAAI, WAO). Pre-2010 GLs scored 1.6-4.6 (23%-67%) and post-2010 GLs scored 2.1-6 (30%-86%), on a 7-point Likert scale. The highest scores went to: German-Austrian-Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT-GL (4.7). These were also the only 3 GLs that received "yes" of both evaluators to the item: "I would recommend this GL for use." The domains of "Stakeholder involvement" and "Rigor of Development" only scored 3/7, and "Applicability" scored the lowest. Strikingly, newer GLs only scored clearly better in "Editorial independence" and "Global evaluation." CONCLUSIONS: In AIT-GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the "Scientific rigor" domain flawed. When resources are limited, transculturizing a high-quality GL might be preferable over developing a GL from zero. Our study and AGREE-II could help to select the best candidate. CLINICAL IMPLICATIONS: We here evaluate allergen immunotherapy guideline (AIT-GL) quality. Only high-quality AIT-GLs should be consulted for AIT management decisions. In low-resource settings, transculturization of these is preferred over developing low-quality guidelines.