Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

BACKGROUND: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs. OBJECTIVE: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part. RESULTS: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma. CONCLUSION: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.

Update on Omalizumab for Urticaria: What's New in the Literature from Mechanisms to Clinic.

PURPOSE OF REVIEW: Since omalizumab has been approved for urticaria, numerous randomized and real-life observational trials have been published. We reviewed the period January 2017-February 2018. RECENT FINDINGS: Omalizumab is effective for the control of urticaria recalcitrant to antihistamines in different populations globally. The ratio of total serum IgE 4-week/baseline ≥2 can predict response with a high likelihood. In observational real-life trials, doses have been adjusted on an individual basis: in some populations, up to two-thirds of the patients can be controlled with 150 mg/month; however, others are still not controlled with 300 mg/month. In these, 150 mg bimonthly could be tried, before up-dosing to 450 mg/month. On the long run (up to 3 years) omalizumab kept its efficacy. In many patients, dosing intervals could be augmented (6-8 weeks, some even more). After a 12-month treatment, about 20% showed long-term remission without relapse. Some biomarkers are being detected. Adjusting omalizumab doses in urticaria patients could enhance efficacy (shortening dosing interval and/or augmenting dose) and save costs (after 12 months: extending dosing interval and/or reducing dose).

Cellular and Molecular Mechanisms of Mast Cells in Atherosclerotic Plaque Progression and Destabilization.

Mast cells (MCs) are commonly recognized for their crucial involvement in the pathogenesis of allergic diseases, but over time, it has come to light that they also play a role in the pathophysiology of non-allergic disorders including atherosclerosis. The involvement of MCs in the pathology of atherosclerosis is supported by their accumulation in atherosclerotic plaques upon their progression and the association of intraplaque MC numbers with acute cardiovascular events. MCs that accumulate within the atherosclerotic plaque release a cocktail of mediators through which they contribute to neovascularization, plaque progression, instability, erosion, rupture, and thrombosis. At a molecular level, MC-released proteases, especially cathepsin G, degrade low-density lipoproteins (LDL) and mediate LDL fusion and binding of LDL to proteoglycans (PGs). Through a complicated network of chemokines including CXCL1, MCs promote the recruitment of among others CXCR2+ neutrophils, therefore, aggravating the inflammation of the plaque environment. Additionally, MCs produce extracellular traps which worsen inflammation and contribute to atherothrombosis. Altogether, evidence suggests that MCs actively, via several underlying mechanisms, contribute to atherosclerotic plaque destabilization and acute cardiovascular syndromes, thus, making the study of interventions to modulate MC activation an interesting target for cardiovascular medicine.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Aeroallergen immunotherapy associated with reduced risk of severe COVID-19 in 1095 allergic patients.

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

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.

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico]. / Resumen ejecutivo de ARIA 2019: Vías integradas de atención para la rinitis alérgica en Argentina, España y México.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

[MASK (Mobile Airways Sentinel Network), a mobile App with ARIA's comprehensive solution in Spanish-speaking countries]. / MASK (Mobile Airways Sentinel Network), una app móvil con la solución integral de ARIA en países de habla hispana.

Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used.

Aunque existen guías clínicas de alta calidad sobre rinitis alérgica, numerosos pacientes reciben tratamiento deficiente, en parte debido al alto grado de automedicación. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS; en ella, los pacientes indican diariamente cuánto les molestan los síntomas a través de cinco pantallas con una escala visual análoga; recientemente se agregaron dos pantallas más (afectación del sueño). La aplicación también permite descargar los datos del "Diario de alergias" en la computadora del médico en el momento de la consulta a través de un código QR. En este artículo reseñamos el primer año de experiencia en España, México y Argentina, que utilizan la versión española.

[MASK (Mobile Airways Sentinel Network). ARIA's comprehensive solution for mobile app for the multimorbidity of allergic rhinitis and asthma]. / MASK (Mobile Airways Sentinel Network). La solución integral de ARIA por app móvil para la multimorbilidad de rinitis alérgica y asma.

The vast majority of patients with allergic rhinitis (AR) do not receive the proper management which is recommended by the guidelines, but they frequently self-medicate. MASK (Mobile Airways Sentinel Network) is an integral part of a project that is supported by the European Union against chronic diseases and focused on active and healthy aging. MASK represents the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma), in which, by using a mobile application in a smart device, the objective is to guide the patient in the control of his/her multi-morbidity, AR and/or allergic conjunctivitis (AC) and/or asthma. The mobile app Allergy Diary by MACVIA-ARIA is free and it is available for both Android and iOS platforms. After it is downloaded to the patient's cell phone, it first requests some information about the patient's profile, allergic pathologies and medication; afterwards, through a visual analog scale, the patient is invited to determine the degree of affectation in the nose, eyes, and bronchi, and its influence on their productivity at work / school. After analyzing the data generated by filling the Allergy Diary, it became clear there is a new clinical entity: allergic rhinitis+ allergic conjunctivitis +asthma, with greater effect; in addition to a high level of self-medication: in general, the patient takes medication on days when symptoms are present. The app has already been deployed in 23 countries, including several Spanish-speaking countries.

La mayoría de los pacientes con rinitis alérgica no recibe el manejo idóneo, sino que se automedica. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS. Al descargarla al celular del paciente, a este se le piden datos de su perfil, patologías alérgicas y medicación; posteriormente, mediante una escala visual analógica se le invita a determinar el grado de afectación en nariz, ojos y bronquios y su influencia sobre su productividad laboral/escolar. Con los datos del Diario de Alergia se observa que existe un nuevo patrón de presentación: rinitis alérgica + conjuntivitis alérgica + asma, con mayor afectación, así como un alto nivel de automedicación: en general, el paciente toma medicación cuando presenta síntomas. La app se ha desplegado en 23 países, incluyendo varios países hispanohablantes.

[GUIMIT 2019, Mexican Guideline on Immunotherapy. Guideline on the diagnosis of IgE-mediated allergic disease and immunotherapy following the ADAPTE approach]. / GUIMIT 2019, Guía Mexicana de Inmunoterapia. Guía de diagnóstico de alergia mediada por IgE e inmunoterapia aplicando el método ADAPTE.

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.