Biologics for the Treatments of Allergic Conditions: Severe Asthma.

By selectively targeting specific steps of the immune inflammation cascade, biologic drugs for severe asthma have substantially contributed to increase the standard of care, to reduce drug-related morbidity. and most importantly to ameliorate patients' quality of life. Upcoming molecules are going to provide a chance for severe phenotypes besides Th2 high through the interaction with epithelial and innate immunity. Some practical aspects including optimal treatment duration, the possibility of a dose treatment modulation, the place and relevance of ICS in best responders are still under debate. Long-term safety, especially when interacting with innate immunity needs to be further investigated.

Global implementation of the world health organization's International Classification of Diseases (ICD)-11: The allergic and hypersensitivity conditions model.

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.

What have recent advances in therapy taught us about severe asthma disease mechanisms?

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.

Changing the history of anaphylaxis mortality statistics through the World Health Organization's International Classification of Diseases-11.

We review the history of the classification and coding changes for anaphylaxis and provide current and perspective information in the field. In 2012, an analysis of Brazilian data demonstrated undernotification of anaphylaxis-related deaths because of the difficulties of coding using the International Classification of Diseases, 10th Revision. This work triggered strategic international actions supported by the Joint Allergy Academies and the International Classification of Diseases World Health Organization (WHO) leadership to update the classification of allergic disorders for the International Classification of Diseases, 11th Revision (ICD-11), which resulted in construction of the pioneer "Allergic and hypersensitivity conditions" chapter. The usability of the new framework has been tested by evaluating the same data published in 2012 from the ICD-11 perspective. Coding accuracy was much improved, reaching 95% for definite anaphylaxis. As the results were provided to the WHO Mortality Reference Group, coding rules have been changed, allowing anaphylaxis to be recorded as an underlying cause of death in official mortality statistics. The mandatory use of ICD-11 from January 2022 for documenting cause of death could have 2 immediate consequences: (1) the reported number of anaphylaxis-related deaths might increase because of more appropriate coding and (2) the cross-sectional and longitudinal mortality data generated might ultimately lead to a better understanding of anaphylaxis epidemiology and improved health policies directed at reducing anaphylaxis-related mortality.

Biological Therapies of Immunologic Diseases: Strategies for Immunologic Interventions.

The immune system possesses a vast number of potential targets for therapeutic intervention. Although therapies for many pathways have been pursued, only few have yielded significant success. Hindrances in altering biologic pathways include the potential for unwanted downstream effects, ineffectiveness owing to biological redundancy, recognition of a therapeutic molecule as foreign by the body's innate immune system, and the risks of subsequent malignancy and/or autoimmunity. This article covers currently available biotherapeutic agent classes as well as potential direction for future therapy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

International Consensus (ICON): allergic reactions to vaccines.

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.

Linkage and Genetic Association in Severe Asthma.

A significant body of work in the genetics of asthma currently exists. However, current knowledge has not been clarifying in understanding the pathophysiology of asthma and therapeutic treatment of the disease. Severe asthma in adults and children is a significant burden in relation to disproportionate disease morbidity, mortality, and health utilization. This disease phenotype is not well understood; current effective treatment regimens are limited. Genetic studies may lead to improved understanding of the pathophysiology of severe asthma and identification of relevant subsets, which allow more targeted and effective therapies and the realization of Precision Medicine in asthma.

Eosinophilic bioactivities in severe asthma.

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.

International survey on skin patch test procedures, attitudes and interpretation.

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.