Pediatric asthma comorbidities: Global impact and unmet needs.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Latin American anaphylaxis registry.

Background: Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective: To provide updated and extended data on anaphylaxis in this region. Method: An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results: Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions: Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

Erratum to "IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper" [World Allergy Organ J 13/2 (2020) 100080].

[This corrects the article DOI: 10.1016/j.waojou.2019.100080.].

The challenges of chronic urticaria part 2: Pharmacological treatment, chronic inducible urticaria, urticaria in special situations.

This is Part 2 of an updated follow-up review of the World Allergy Organization (WAO) position paper on the diagnosis and treatment of urticaria and angioedema. Since that document was published, new advances in the understanding of the pathogenesis of chronic urticaria, and greater experience with the use of biologics in patients with severe refractory disease, mainly omalizumab, have been gained. For these reasons, WAO decided to initiate an update targeted to general practitioners around the world, incorporating the most recent information on epidemiology, immunopathogenesis, comorbidities, quality of life, clinical case presentations, and the management of chronic spontaneous and chronic inducible urticaria, and urticaria in special situations such as childhood and pregnancy. A special task force of WAO experts was invited to write the different sections of the manuscript, and the final document was approved by the WAO Board of Directors. This paper is not intended to be a substitute for current national and international guidelines on the management of urticaria and angioedema, but to provide an updated simplified guidance for physicians around the world who have to manage patients with this common ailment.

Wheezing-Related Relevant Factors and the Role of Viral Bronchiolitis.

Bronchiolitis is a virus-associated infection of the lower respiratory tract exhibiting signs and symptoms of airway obstruction. Respiratory Syncytial Virus (RSV) is responsible in most cases; however, different rhinoviruses have also been implicated. Specific viruses and time until the first infection, severity of the respiratory condition, and atopic status have a determinant role in the recurrence of wheezing and asthma development. Genetics, lung function, atopic condition, the role of microbiota and environment, pollution, and obesity are considered in the present review. Emergency room visits and hospitalizations because of severe wheezing and smoking during pregnancy among others were identified as risk factors for significant morbidity in our population. Approaching determinant conditions like genetics, allergy, antiviral immunity, and environmental exposures such as farm vs. urban and viral virulence provides an opportunity to minimize morbidity of viral illness and asthma in children.

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.

[Allergic rhinitis' treatment in children in Argentina. Update]. / Tratamiento de la rinitis alérgica en pediatría en Argentina. Documento de actualización

Allergic rhinitis (AR) is the most frequent allergic disease. Prevalence in children and teenagers in Argentina ranges between 22.3% and 34.9%. Given this situation, members of the scientific committees of Pediatrics and Rhinitis of the Argentinian Association of Allergy and Clinical Immunology (AAAeIC) have reviewed scientific evidence in order to update the therapeutic regulations of this pathology in the pediatric population. The classification and categorization of AR are currently in full review all around the world. It is necessary to make a differential diagnosis with other non-allergic types of rhinitis in children, and to confirm AR based on the clinical history, physical examination, determination of bio-markers, and/or skin tests. Non-pharmacological treatment includes education and guidelines of environmental control for allergens such as dust mites, anemophilous fungi, animal epithelium, and pollens. Step pharmacological therapy is proposed according to the control of the disease. Second-generation, non-sedating anti-histamines are the first line of therapy. The association with oral decongestants is not recommended in children under 4 years of age. Inhaled corticosteroids are the first choice for both moderate and severe forms. This document warns pediatricians about the importance of an early diagnosis, the rational use of step pharmacological therapy, and specific immunotherapy in children.

La rinitis alérgica (RA) es la enfermedad alérgica más frecuente. La prevalencia en niños y adolescentes de Argentina oscila entre 22.3 y 34.9 %. Ante esto, integrantes de los comités científicos de pediatría y rinitis de la Asociación Argentina de Alergia e Inmunología Clínica (AAAeIC) revisaron evidencia científica para actualizar las normativas terapéuticas de esta patología en la población pediátrica. La clasificación y categorización de la RA se encuentra actualmente en plena revisión en todo el orbe. Es necesario realizar un diagnóstico diferencial con otras rinitis no alérgicas en los niños, y confirmar la RA con base en la historia clínica, el examen físico, la determinación de biomarcadores o pruebas cutáneas. El tratamiento no farmacológico incluye la educación y pautas de control ambiental para alérgenos como ácaros, hongos anemófilos, epitelio de animales y pólenes. Se propone un tratamiento farmacológico escalonado de acuerdo con el control de la enfermedad. Los antihistamínicos de segunda generación no sedativos son la primera línea de tratamiento. La asociación con descongestivos orales no se recomienda en menores de cuatro años. Los corticoides nasales inhalados son de primera elección en formas moderadas y graves. El presente documento alerta a los pediatras sobre la importancia del diagnóstico precoz, el uso racional del tratamiento farmacológico escalonado y la inmunoterapia específica en niños.

[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.

[2017 Brussels Agreement for Latin America: an initiative of the GARD and Slaai]. / El Acuerdo Bruselas 2017 para Latinoamérica: una iniciativa de la GARD y Slaai.

The Global Alliance against Chronic Respiratory Diseases (GARD) is a network of organizations coordinated by the World Health Organization. It is a voluntary alliance of national and international organizations, institutions and agencies with global scope that are committed with actions to improve access to prevention, care and essential medications. On its last annual meeting, celebrated in Brussels (Belgium) in September 2017, the need for actions and representation to be grouped by geographic regions was discussed. There are several successful programs regarding morbidity and mortality control of these diseases, and others that improve cost-benefit and quality of life. Thus, SLaai proposes to contribute to the diffusion and knowledge of chronic respiratory diseases magnitude and risk factors, to identify successful programs in Latin America in order for them to be replicated in the region and to generate strategic alliances for the strengthening of joint actions.

La Alianza Global contra las Enfermedades Respiratorias Crónicas es una red de organizaciones coordinadas por la Organización Mundial de la Salud. Es una coalición voluntaria de organizaciones, instituciones y organismos nacionales e internacionales con alcance mundial comprometidos con acciones para mejorar el acceso a la prevención, asistencia y medicamentos esenciales. Durante su última reunión anual, efectuada en Bruselas, Bélgica, en septiembre de 2017, emergió la necesidad de agrupar acciones y representación por regiones geográficas. Existen diferentes programas exitosos en el control de la morbimortalidad de estas enfermedades y otros que mejoran el costo-beneficio y la calidad de vida. Así, desde SLaai se propone contribuir a la difusión y conocimiento de la magnitud y factores de riesgo en enfermedades respiratorias crónicas, identificar programas exitosos de Latinoamérica para ser replicados en la región y generar convenios estratégicos para el fortalecimiento de acciones conjuntas.

Current status of therapy with omalizumab in children.

PURPOSE OF REVIEW: There are a considerable number of patients with moderate-to-severe uncontrolled asthma needing additional therapy. Omalizumab, an anti-IgE monoclonal antibody, improves control while reducing IgE-mediated airway inflammation and potentially interfering in the progressive remodeling process. The clinical implications are reductions in the required doses of inhaled steroids, a decrease in exacerbation number, and a reduction in emergency room visits and hospitalizations. In addition to its use in asthma, there is an increasing interest on the use of omalizumab for other uncontrolled IgE-mediated diseases, supported by the favorable risk-benefit background. The present review explores the most recent publications on the use of omalizumab for allergic asthma and other atopic conditions in children. RECENT FINDINGS: Omalizumab has also shown efficacy in allergic rhinitis, and it is being investigated in the treatment of anaphylaxis, food allergy, atopic dermatitis, and chronic spontaneous urticaria, as well as cystic fibrosis and allergic bronchopulmonary aspergillosis. Despite the benefits shown so far, more data are needed for optimal use in these conditions, particularly looking at the safety issues that have to be confirmed. SUMMARY: Confirmatory evidence on the efficacy and safety of omalizumab in children is reviewed, as well as newest fields of applicability in which IgE is involved in disease mechanism.

Diagnosis of occupational asthma: an update.

Work-related asthma (WRA) includes patients with sensitizer- and/or irritant-induced asthma in the workplace, as well as patients with preexisting asthma that is worsened by work factors. WRA is underdiagnosed; thus, the diagnosis is critical to prevent disease progression and its potential for morbidity and mortality. The interview is the first diagnostic tool to be used by physicians, and the question, "Does asthma improve away from work?" is of the highest sensitivity. However, history can show numerous false positives, and the relationships between asthma worsening and work should be confirmed by objective methods such as peak expiratory flow (PEF) at and away from work. PEF sensitivity and specificity can be enhanced in combination with nonspecific bronchial hyperresponsiveness to histamine/methacholine (NSBP) before and after 2 weeks at work and a similar period off work. Immunologic testing, especially skin prick test (SPT) or specific IgE, is useful for high molecular weight allergens and some low molecular weight agents. Other immunologic tests, as well as induced sputum, measurement of exhaled nitric oxide, exhaled breath condensate, and specific inhalation challenge (SIC) are methods that contribute to the diagnosis and are typically performed at specialized facilities. A diagnosis of occupational asthma (OA) should no longer be based on a compatible history only but should be confirmed by means of objective testing. SIC is the diagnostic gold standard. When SIC is not available, the combination of PEF measurement, NSBP test , a specific SPT, or specific IgE may be an appropriate alternative in diagnosing OA.

Impact of environmental tobacco smoke and active tobacco smoking on the development and outcomes of asthma and rhinitis.

PURPOSE OF REVIEW: We aim to discuss current insights on the influence of active smoking and environmental tobacco smoke in lower and upper respiratory inflammatory illnesses. RECENT FINDINGS: Insight has been gained on the effect of tobacco smoking on the development of asthma from the womb to adolescence. Secondhand tobacco exposure and active smoking play a major role not only in the inception of asthma epidemiological community studies but also in patients already suffering from allergic rhinitis. Tobacco seems to influence innate immunity predisposing to Th2-associated respiratory diseases and increasing the risk for IgE-mediated sensitization. Tobacco smoking is related to worst outcomes in both asthma and rhinitis. SUMMARY: Several deleterious effects have been described in asthma because of smoking: accelerated decline in lung function, more severe symptoms, impairment in quality of life and diminished therapeutic response to steroids. The harmful effect of tobacco smoking is not only on asthma but also on rhinitis playing a role in disease outcomes. Tobacco exposure can influence innate immunity diminishing innate production of antigen-presenting cells cytokines, as well as an impaired response to toll-like receptor ligands. Active smoking is associated with current symptoms of asthma and rhinitis and seems to be a risk factor for developing new asthma in patients with rhinitis. Tobacco smoking has been also found among the factors inducing nasal obstruction and decreased muco-ciliary clearance in nonallergic rhinitis.