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The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD‐11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD‐11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD‐11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD‐11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients. [ABSTRACT FROM AUTHOR]

Introduction: Severe asthma still represents a worldwide challenge. The need for further treatment options has stimulated basic and pharmacological research to focus on the immune and inflammatory background of asthma. The new biologic drugs express the considerable advances in the field and besides providing a revolutionary treatment option for severe asthma, contribute themselves to better understand the pathophysiologic mechanisms they address, paving the way to new potential targets. Areas covered: A selective search on PubMed and Medline was performed, including the evidence on immunology of severe asthma published up to May 2019 by focusing on the immunological effects of biologic drugs underlying their clinical outcomes. Expert opinion: The recent pharmacological research in the field of biologics has represented an exceptional opportunity for exploring severe asthma mechanisms. However, some points deserve to be addressed by further investigation. Although in the absence of safety warnings so far, interfering with the immune system may raise some safety concerns, especially in the long-term use. Particularly when interacting with epithelial and innate immunity the selection of candidates probably deserves special caution. Also, whether biologics exert a true disease-modifying effect is not completely clear. As a direct practical implication, the optimal treatment duration is still controversial. [ABSTRACT FROM AUTHOR]

Background: Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. Methods: Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/ immunologists as well as vaccinologists. Results: Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. Conclusions: This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines. [ABSTRACT FROM AUTHOR]

Asthma is clearly related to airway or blood eosinophilia, and asthmatics with significant eosinophilia are at higher risk for more severe disease. Eosinophils actively contribute to innate and adaptive immune responses and inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors. Eosinophils may persist in the blood and airways despite guidelines-based treatment. This review details eosinophil effector mechanisms, surface markers, and clinical outcomes associated with eosinophilia and asthma severity. There is interest in the potential of eosinophils or their products to predict treatment response with biotherapeutics and their usefulness as biomarkers. This is important as monoclonal antibodies are targeting cytokines and eosinophils in different lung environments for treating severe asthma. Identifying disease state-specific eosinophil biomarkers would help to refine these strategies and choose likely responders to biotherapeutics. [ABSTRACT FROM AUTHOR]

Background: Skin patch test is the gold standard method in diagnosing contact allergy. Although used for more than 100 years, the patch test procedure is performed with variability around the world. A number of factors can influence the test results, namely the quality of reagents used, the timing of the application, the patch test series (allergens/haptens) that have been used for testing, the appropriate interpretation of the skin reactions or the evaluation of the patient's benefit. Methods: We performed an Internet-based survey with 38 questions covering the educational background of respondents, patch test methods and interpretation. The questionnaire was distributed among all representatives of national member societies of the World Allergy Organization (WAO), and the WAO Junior Members Group. Results: One hundred sixty-nine completed surveys were received from 47 countries. The majority of participants had more than 5 years of clinical practice (61 %) and routinely carried out patch tests (70 %). Both allergists and dermatologists were responsible for carrying out the patch tests. We could observe the use of many different guidelines regardless the geographical distribution. The use of home-made preparations was indicated by 47 % of participants and 73 % of the respondents performed 2 or 3 readings. Most of the responders indicated having patients with adverse reactions, including erythroderma (12 %); however, only 30 % of members completed a consent form before conducting the patch test. Discussion: The heterogeneity of patch test practices may be influenced by the level of awareness of clinical guidelines, different training backgrounds, accessibility to various types of devices, the patch test series (allergens/ haptens) used for testing, type of clinical practice (public or private practice, clinical or research-based institution), infrastructure availability, financial/commercial implications and regulations among others. Conclusion: There is a lack of a worldwide homogeneity of patch test procedures, and this raises concerns about the need for standardization and harmonization of this important diagnostic procedure. [ABSTRACT FROM AUTHOR]

MILAN gl GLO:1X5/01jun21:all14869-fig-0002.jpg PHOTO (COLOR): 2 World Allergy Organization (WAO) BOARD OF DIRECTORS 2016-2017 with a few incoming 2018-2019 WAO BOARD at WAO Symposium, 2017, Cartegena, Columbia gl Prof. Mario Sánchez Borges also actively contributed to organizations such as the American Academy of Allergy, Asthma and Immunology (AAAAI), Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC), European Academy of Allergy and Clinical Immunology (EAACI), and the Collegium Internationale Allergologicum (CIA) and was awarded the International Distinguished Fellow Award of the American College of Allergy, Asthma and Immunology (ACAAI). Ruby Pawankar (WAO President, 2012-2013), Lanny J Rosenwasser (WAO President, 2014-2015), Giorgio Walter Canonica (WAO President, 2008-2009) ACKNOWLEDGEMENTS We thank all the WAO Board of Directors and WAO secretariat for their valuable contribution during these years of our WAO Presidencies and Prof. Mario Sanchez Borges's WAO Presidency. He contributed to the many WAO initiatives like the Guidelines, the WAO White Book, World Allergy Congresses (WAC), and the WAO's International Scientific Conferences (WISC) and led many of them. [Extracted from the article]

Objective. Asthma is a chronic disease that affects millions of people. Messenger RNA (mRNA) expression of specific inflammatory markers has been associated with asthma and corticosteroid response. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been shown to have increased expression in airways of asthmatics and may be related to corticosteroid sensitivity. The purpose of this study was to determine how genetic variants within the promoter region of the TNFA gene differ between subjects with asthma and controls. We also investigated how genetic variation affects gene expression. Methods. We enrolled 94 subjects between 5 to 54 years of age who met the inclusion and exclusion criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and -308G/A on genomic DNA isolated from blood with commercially available assays. Gene expression was log-2 transformed and corrected with 2 normalization genes. General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel-Haenszel test were performed with p < .05. Results. The TNFA-857C/T polymorphism is associated with asthma in this cohort. The TNFA-857 T allele is underrepresented in pediatric subjects with asthma relative to those without asthma (3% and 29% of individuals, respectively, p = .01). Furthermore, a TNFA haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is associated with lower expression of TNF-α mRNA ( p = .01) in pediatric subjects. Conclusions. Presence of the TNFA-857T allele may be protective in the development of asthma and a haplotype combination that contains the TNFA-857T allele is associated with TNFA expression. [ABSTRACT FROM AUTHOR]

Background Differences in mRNA expression for inflammatory markers have been observed between subjects with asthma vs. controls and in relation to corticosteroid response. However, these studies utilized methods (e.g., bronchoscopy) that are too invasive to be used routinely in children and in the clinic. The primary purpose of this study was to determine the feasibility of obtaining RNA of adequate quantity and quality from buccal mucosa of children and adults for gene expression studies. Secondly, this study aimed to determine whether gene expression patterns in buccal mucosa are similar to those that have been observed in respiratory epithelium. Methods We enrolled 94 subjects with and without asthma between 5 and 54 years of age. Relative gene expression in buccal mucosa was determined with quantitative RT- PCR for the following genes: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, CLCA1, CRHR1, MUC5B, FCER2, POSTN, GAPDH, PPIA. Results m RNA Expression of the following genes was detected in buccal mucosa: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, GAPDH, PPIA. HRH1 was differentially expressed in adults with asthma vs. controls (p = 0.04), and EDN1 was differentially expressed in children with asthma vs. controls 12-18 years old (p = 0.03). A similar trend for HRH1 was observed in children 12-18 years old. Conclusions Buccal mucosa sampling is a reliable method for detecting changes in gene expression in patients with asthma. This non-invasive technique may serve as a valuable tool for diagnosing asthma and evaluating therapeutic response. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting β2-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented. Objective: To compare the efficacy and safety of budesonide/formoterol pressurised metered-dose inhaler (budesonide/formoterol pMDI; Symbicort™ pMDI, AstraZeneca LP, Wilmington, DE, USA) with budesonide pMDI (Pulmicort™ DPI, AstraZeneca, Lund, Sweden), formoterol DPI (Oxis® Turbuhaler®, AstraZeneca, Lund, Sweden), budesonide plus formoterol in separate inhalers (budesonide pMDI + formoterol DPI) and placebo. Study design: This was a 12-week randomised, double-blind, double-dummy, placebo-controlled study. Setting: This multicentre study was conducted in the respiratory specialty clinical practice setting. Patients: The study included 596 patients ≥12 years of age with moderate to severe persistent asthma previously receiving ICSs. interventions: After 2 weeks on budesonide pMDI 80μg × two inhalations (160μg) twice daily, patients received budesonide/formoterol pMDI 160μg/4.5μg × two inhalations (320μg/μg); budesonide pMDI 160μg × two inhalations (320μg) + formoterol DPI 4.5μg × two inhalations (9μg); budesonide pMDI 160μg × two inhalations (320μg); formoterol DPI 4.5μg × two inhalations (9μg); or placebo twice daily. [ABSTRACT FROM AUTHOR]

In 2004 the World Allergy Organization’s Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: A single nucleotide polymorphism (SNP) C-509T within the tumor growth factor β1 (TGFβ1) gene has been associated with atopic asthma and asthma severity. To further understand the mechanisms involved, the association of C-509T with allergy, T-lymphocyte proliferation and plasma TGFβ1 concentration has been explored in a case-control study with allergic and non-allergic subjects. Methods: The recruited subjects including allergic (n = 38) and nonallergic (n = 25) participants have been genotyped for C-509T using allele discrimination assay. Association of C-509T with allergy status was examined using logistic regression analysis in both dominant and recessive models. Association of C-509T with T-cell proliferation in control and antigen-stimulated peripheral blood mononuclear cells (PBMCs), plasma TGFβ1 and total IgE level were tested by multiple regression analysis. Results: Individuals with homozygous mutant TT genotype showed a higher risk of allergy (TT: odds ratio = 5.099, 95% confidence limit: 1.355–19.190, p = 0.016) after covariates were adjusted. A trend to increased plasma TGFβ1 in subjects with T allele has been discovered. In the meantime, the T allele is associated with lower T cell proliferation in controls and maximum response to above antigens. A low T-cell proliferation is correlated with higher plasma TGFβ1 concentration (p < 0.01). The in vitro studies confirmed the suppressing effect of TGFβ1 on T-cell proliferation at physiological range. A significant inhibitory effect on IL-4 production was also observed. Conclusions: A C to T base change in TGFβ1 SNP C-509T has been associated with a higher risk of allergy. The mechanisms are not clear. Elevated TGFβ1 levels associated with the C-509T polymorphism might suppress immune activation as well as Th2 cytokine production. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The α[sub 4] integrin, as α[sub 4] β[sub 1] (VLA-4) or α[sub 4] β[sub 7] , is critical for T cell migration and proliferation, although its functional modulation remains poorly understood. We hypothesized that increased receptor density, based on new receptor chain synthesis, was one such mechanism. We examined the surface receptor density of the α[sub 4] and β[sub 1] chains on CD4+CD45RO+ cells, and the mRNA expression of these and the β[sub 7] chain in response to allergen and nonallergen antigen stimulation. Methods: Flow-cytometric analyses for CD49d, CD29, and CD45RO were performed on T cell lines specific for timothy, tetanus, and Candida from atopic and nonatopic donors. RNA was extracted from cells sorted to select CD4+/CD49d-positive cells before and after stimulation. Equivalent amounts of cDNA for β-actin, α[sub 4] , β[sub 1] and β[sub 7] were used in PCR, and the products were quantified using phosphoimaging. Results: CD49d expression is heterogeneous on T cell lines and is upregulated by antigen stimulation on CD4+ T cells. The surface expression on CD4+CD45RO+ timothy allergen or tetanus toxoid T cell lines is at least double that found on CD45RO– cells. Antigen stimulation upregulated CD49d expression on the CD4+CD45RO+ subpopulation of both cell lines although it was not as significant as in the case of all CD4+ T cells. CD29 surface expression behaves similarly. Candida had no effect on CD49d or CD29. Messenger RNA expression for the α[sub 4] chain (CD49d) is significantly upregulated 48 h following the addition of timothy or tetanus. β[sub 7] chain expression also rises significantly on both cell lines. β[sub 1] chain expression increases, but not significantly. Conclusions: The surface expression of the CD49d is heterogeneous and much higher on CD4+CD45RO+ cells than on CD4+RO– T cells. The CD49d integrin chain on CD4+ T cells is upregulated following antigen exposure. However, the CD4+CD45RO+ subpopulation is only partially responsible for this increase suggesting other T cells to have this receptor expression upregulated. CD29 expression behaves similarly. Messenger RNA expression increases coordinately for α[sub 4] , β[sub 7] , and not significantly for β[sub 1] in these cells. These observations provide a potential mechanism for the selective accumulation of T cells at sites of inflammation, and suggest an important point of intervention for allergic and inflammatory disease.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents Chapter 20 of the `Primer on Allergic and Immunologic Diseases,' published by the `Journal of the American Medical Association.' The two events that revolutionized the fied of immunohematology; Autoimmune hemolytic anemias; Paroxysmal cold hemoglobinuria; Drug-induced hemolytic anemias; Hemolytic diseases of the newborn; Eosinophilic diseases.

This paper will review genetic variations in the structure of three important candidate genes with varying effects in atopy and asthma that may have significant overall susceptibility associations in relation to the development of atopy and asthma. The three cytokine genes involved are interleukin (IL)–4, IL–9 and transforming growth factor β1, and the nature of the polymorphisms may be related to significantly higher outputs of these cytokines in atopy and asthma. [ABSTRACT FROM AUTHOR]