Consenso mexicano en relación con la fracción exhalada de óxido nítrico (FeNO) en asma 2020

La fracción exhalada de óxido nítrico (FeNO) se relaciona con el nivel de inflamación eosinofílica en las vías aéreas y los niveles de interleucina-13, por lo que podría ser una herramienta diagnóstica y de seguimiento en el asma. Se convocó un grupo de trabajo integrado por neumólogos, expertos en fisiología de la respiración y alergólogos, con la finalidad de establecer criterios para el uso de la FeNO en asma en México. Mediante un método Delphi simplificado y discusión grupal, se consensaron varios puntos clave en relación con el uso de la FeNO. Sugerimos que la medición de la FeNO sirve para el diagnóstico de asma en clínicas especializadas, tanto en niños como adultos, así como para determinar el nivel de tratamiento con corticosteroides. En asma grave, recomendamos la FeNO para la endotipificación, detectar la mala adherencia terapéutica, el subtratamiento y el riesgo de crisis. Sugerimos su uso para determinar el nivel de tratamiento con corticosteroides e identificar pacientes con riesgo de tener una pérdida de la función pulmonar. También la recomendamos en el adulto para mejorar la elección de medicamentos biológicos y, en este contexto, solo la sugerimos en casos selectos en niños

Consenso mexicano para el diagnóstico y tratamiento de la dermatitis atópica en adolescentes y adultos

Abstract Background: The diagnostic approaches and therapeutic strategies of atopic dermatitis (AD) are generally inconsistent among physicians and health institutions. Objective: To develop a consensus statement among experts to reduce the variations in practice regarding the diagnosis and treatment of patients ≥ 12 years with AD to improve their care. Methods: Systematic literature search in PubMed and GREAT. With methodological support and using the Delphi method, a formal consensus was developed among 16 experts in Dermatology and Allergology, based on the current evidence and its applicability in the Mexican context. Apart from intense electronic communication, several issues of disagreement were discussed in two face-to-face meetings. Results: The clinical experts reached consensus on 46 statements related to the definition, classification, diagnostic strategies and treatment of AD. For the diagnosis we suggest the Williams criteria and for severity scoring the SCORAD (by the doctor) and POEM (by the patient). In addition to general care and treatment education (workshops), we suggest four steps for treatment, depending on severity: 1. Topical treatment with anti-inflammatory agents (and systemic: antihistamines/antileukotrienes —low level evidence—) 2. Phototherapy, 3. Cyclosporin A and 4. Dupilumab, with the possibility of managing this biological earlier on if a fast effect is needed. In extrinsic AD we suggest evaluating the addition of allergen immunotherapy or an elimination diet, if there is an IgE-mediated respiratory or food allergy, respectively. Conclusion: The panel of experts reached consensus on relevant aspects of AD with a focus on the transcultural adaptation of recent evidence. Keywords: Atopic dermatitis; Atopic dermatitis treatment; Consensus; Cyclosporin A; Biological treatment; Dupilumab; Omalizumab. Resumen Antecedentes: Los abordajes diagnósticos y las estrategias terapéuticas de la dermatitis atópica generalmente son inconsistentes entre los médicos y entre las instituciones de salud. Objetivo: Consensar las opiniones de expertos para reducir las variaciones en la práctica respecto al diagnóstico y tratamiento de pacientes ≥ 12 años con dermatitis atópica para mejorar su cuidado. Métodos: Búsqueda sistemática de la literatura en PubMed y GREAT. Con apoyo metodológico y utilizando el método Delphi se desarrolló un consenso formal entre 16 expertos en dermatología y alergología, basándose en la evidencia actual y su aplicabilidad en el contexto mexicano. A parte de una comunicación electrónica intensa, se discutieron los puntos en desacuerdo en dos reuniones presenciales. Resultados: Los expertos clínicos alcanzaron consenso en 46 declaraciones relacionadas con la definición, clasificación, estrategias de diagnóstico y tratamiento de la dermatitis atópica. Para el diagnóstico sugerimos se usan los criterios de Williams y el SCORAD (por parte del médico) y POEM (por parte del paciente) para definir la gravedad. Aunado a cuidados generales y educación terapéutica, sugerimos cuatro pasos para tratamiento, según gravedad: 1. Manejo tópico con antiinflamatorio (y sistémico: antihistamínico/ antileucotrieno —evidencia reducida—) 2. Fototerapia, 3. Ciclosporina A y 4. Dupilumab, con la posibilidad de manejarlo antes si se necesita efecto rápido. En la dermatitis atópica extrínseca sugerimos agregar inmunoterapia con alérgenos o una dieta de eliminación si existe una alergia IgE-mediada, inhalatoria o alimentaria, respectivamente. Conclusión: El panel de expertos realizó consenso en aspectos relevantes de la dermatitis atópica con enfoque en la adaptación transcultural de evidencia reciente. Palabras clave: Dermatitis atópica; Ciclosporina A; Tratamiento biológico; Dupilumab; Omalizumab; Posición de consenso

Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics

Background: Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age. Methods: In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes. Results: 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005). Conclusions: In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens –some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries

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, see 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

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular diagnosis in the near future

Percutaneous skin prick tests (SPT) have been considered the preferred method for confirming IgE-mediated sensitization. This reliable and minimally invasive technique correlates with in vivo challenges, has good reproducibility, is easily quantified, and allows analyzing multiple allergens simultaneously. Potent extracts and a proficient tester improve its accuracy.Molecular-based allergy diagnostics (MA-Dx) quantifies allergenic components obtained either from purification of natural sources or recombinant technology to identify the patient’s reactivity to those specific allergenic protein components. For a correct allergy diagnosis, the patient selection is crucial. MA-Dx has been shown to have a high specificity, however, as MA-Dx testing can be ordered by any physician, the pre-selection of patients might not always be optimal, reducing test specificity. Also, MA-Dx is less sensitive than in vitro testing with the whole allergen or SPT. Secondly, no allergen-specific immunotherapy (AIT) trial has yet shown efficacy with patients selected on the basis of their MA-Dx results. Thirdly, why would we need molecular diagnosis, as no molecular treatment can yet be offered? Then there are the practical arguments of costs (SPT highly cost-efficient), test availability for MA-Dx still lacking in wide areas of the world and scarce in others. As such, it is hard physicians can build confidence in the test and their interpretation of the MA-Dx results. In conclusion: as of now these techniques should be reserved for situations of complex allergies and polysensitization; in the future MA-Dx might help to reduce the number of allergens for AIT, but trials are needed to prove this concept. Keywords: Allergens, Skin testing, Prick testing, Specific IgE, Molecular allergy diagnostics, Peanut, Oral allergy syndrom

MASK (Mobile Airways Sentinel Network), una app móvil con la solución integral de ARIA en países de habla hispana

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.Fil: Larenas Linnemann, Désirée. Fundación Clínica Médica Sur; ArgentinaFil: Mullol, Joaquim. Universitat de Barcelona; EspañaFil: Ivancevich, Juan Carlos. Clínica Santa Isabel; ArgentinaFil: Anto, Josep M. Universitat Pompeu Fabra; EspañaFil: Cardona, Victoria. Hospital Vall d’Hebron; EspañaFil: Dedeu, Toni. European Regional and Local Health Association; BélgicaFil: Rodríguez González, Mónica. Hospital Español; MéxicoFil: Huerta Villalobos, Yunuen Rocío. Instituto Mexicano del Seguro Social; MéxicoFil: Neffen, Hugo. Center of Allergy; ArgentinaFil: Fuentes Pérez, José Miguel. Instituto Mexicano del Seguro Social; MéxicoFil: Rodríguez Zagal, Endira. Instituto Mexicano del Seguro Social; MéxicoFil: Valero, Antonio. Universidad de Barcelona; EspañaFil: Zernotti, Mario Emilio. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; ArgentinaFil: Bartra, Joan. Hospital Clínic; EspañaFil: Alobid, Isam. Hospital de La Fe; EspañaFil: Castillo Vizuete, José Antonio. Hospital Universitari Quirón; EspañaFil: Dordal, Teresa. Hospital Municipal Badalona; EspañaFil: Hijano, Rafael. Hospital del Mar; EspañaFil: Picado, César. European Federation of Allergy and Respiratory; España Diseases PatientsFil: Sastre, Joaquín. Fundación Jiménez Díaz; EspañaFil: Blua, Ariel Eduardo. Hospital Privado Universitario de Córdoba; ArgentinaFil: Jares, Edgardo. Sociedad Latinoamericana de Alergia; ArgentinaFil: Lavrut, Alberto Jorge. Hospital General de Niños Pedro de Elizalde; ArgentinaFil: Máspero, Jorge. Fundación Centro de Investigación de Enfermedades Alérgicas y Respiratorias; ArgentinaFil: Bedolla Barajas, Martín. Centro Médico Zambrano Hellion; MéxicoFil: Burguete Cabañas, María Teresa. Hospital Ángeles de Puebla; MéxicoFil: García Cobas, Cecilia Yvonne. Hospital Star Médica Aguascalientes; ArgentinaFil: García Cruz, María de la Luz Hortensia. Hospital Ángeles de Puebla; MéxicoFil: Hernández Velázquez, Luiana. 8Universidad Autónoma de Baja California Campus Ensenada; MéxicoFil: Luna Pech, Jorge A. Universidad de Guadalajara; MéxicoFil: Matta, Juan José. Instituto Mexicano del Seguro Social; MéxicoFil: Mogica Martínez, María Dolores. Instituto Mexicano del Seguro Social; MéxicoFil: Rivero Yeverino, Daniela. Universidad Autónoma de Puebla; ArgentinaFil: Ruiz, Lucy Tania. Instituto Mexicano del Seguro Social; MéxicoFil: Del Río Navarro, Blanca E. Hospital Infantil de México; MéxicoFil: Gómez Vera, Javier. Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado; MéxicoFil: Macías Weinmann, Alejandra. Universidad Autónoma de Nuevo León; MéxicoFil: Murray, Ruth. MedScript Ltd; IrlandaFil: Onorato, Gabrielle. MACVIA-France; FranciaFil: Laune, Daniel. Kyomed; FranciaFil: Bedbrook, Anna. MACVIA-France; FranciaFil: Bousquet, Jean. Université Versailles St-Quentin-en-Yvelines; Franci