Consensus on treatment goals in hereditary angioedema : a global Delphi initiative

Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. Methods: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Results: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients’ lives. Conclusions: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients

Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders

Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against \u3e 15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history

High ambient levels of grass, weed and other pollen are associated with asthma admissions in children and adolescents:A large 5-year case-crossover study

Background: Pollen is an important aeroallergen that triggers asthma exacerbations in children, but we know little about the impact of different pollen types in cities with varying climatic conditions and pollen seasons. Objectives: We aimed to assess the role of ambient level of different types of pollen on a large time series of child and adolescent asthma hospitalizations in Sydney, Australia. Methods: Childhood asthma hospitalization and the daily ambient pollen concentrations of different species were collected in South‐West Sydney. With a bidirectional case‐crossover design, we fitted conditional logistic regression models to measure the associations between instantaneous and up to 3 days lagged effects of pollen concentrations on asthma hospitalizations after controlling for potential confounders and testing for interactions. Results: A total of 2098 children, more boys (59.7%) and 2‐5 years old (62.6%), were hospitalized due to asthma. The geometric mean concentration of Cupressus, 7.88 [5.02] grains/m3, was the highest during the study period. The increase from 75th to 90th percentile of grass (OR = 1.037, 95% CI 1.005‐1.070), weed other than Plantago species (OR = 1.053, 95% CI 1.009‐1.098) and unclassified pollen (OR = 1.034, 95% CI 1.010‐1.058) were significantly associated with the odds of asthma hospitalizations. Boys were at greater risk of asthma exacerbations associated with grass (OR = 1.046, 95% CI 1.003‐1.090) and unclassified pollen (OR = 1.041, 95% CI 1.010‐1.073). There was evidence of effect modification by age groups for Cupressus, conifer, total tree and total pollen. Conclusions: Although boys are more vulnerable to grass pollen, weed, and other pollen are also important triggers of asthma exacerbations in all children and adolescents. These findings are important for urban green space planning and the development of pollen monitoring systems for families with children at risk of asthma exacerbations during peak pollen seasons

Defining a severe asthma super-responder : findings from a Delphi process

Background: Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective: To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods: The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results: Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions: This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs

Debunking the myth of wool allergy:Reviewing the evidence for immune and non-immune cutaneous reactions

Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30–32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.Full Tex

The role of outdoor fungi on asthma hospital admissions in children and adolescents: a 5-year time stratified case-crossover analysis

Background Some fungal spores can trigger asthma exacerbation but knowledge of which outdoor fungal spores contribute to asthma hospitalisation is limited. Objectives To examine the role of outdoor fungal spores in child and adolescent asthma hospitalisations. Methods We conducted a bi-directional time-stratified case-crossover study of child and adolescent asthma hospitalisations over 5 years. Conditional logistic regression assessed the role of 20 fungi taxa (Same day [L0] and lagged [L1-3]) adjusted for maximum temperature, humidity and grass pollen. Strata specific effects were explored if there was evidence of effect modification by age, sex, air pollutants or grass pollen. Non-linear effects examined with Generalized Additive Models. Results Of 2098 children hospitalised for asthma, 60% were boys; mean age was 5.5±3.7 years. Fungal spore counts peaked during warm months. Regression models found weak associations with Coprinus [L0,L1: OR=1.03, 1.01–1.06], Periconia [L0: OR=1.03, 1.001–1.07] and Chaetomium [L2: OR=1.08, 1.0–1.2]. Sex appeared to act as an effect modifier with girls having stronger associations with Cladosporium, Coprinus and total fungi. Older adolescent (14–18 years) hospitalisation was significantly associated with Coprinus and Ustilago/smuts. Air pollutants and grass pollen did not appear to act as effect modifiers. Non-linearity was not detected. Conclusion There may be associations between some outdoor fungal spores and asthma hospitalisations. Further research needed to explore whether these findings can be replicated; and examine whether fungal sensitisation and/or human rhinovirus infections are associated with stronger effects. If findings are replicated, then the need to develop predictive models for fungal spore distribution and levels may become more important

Subcutaneous Gammanorm® by pump or rapid push infusion: Impact of the device on quality of life in adult patients with primary immunodeficiencies.

Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), secondary endpoints were QoL (SF36v2), satisfaction (TSQM-11), disease and treatment burden (PRISM), incidence of infections and adverse events (AE), treatment costs, and IgG levels. 28/30 patients completed the study. Most of the endpoints were comparable. Drug administrations with rapid push were more frequent, but reduced total time expenditure and some costs. Of the TSQM-11/LQI/SF36 components only "treatment interference with daily activities" was superior with pump and two QoL domains with rapid push. Both delivery devices showed favorable safety. Rapid push was preferred by 34.5% of patients. It proved to be an efficacious and cost-effective alternative to pumps adding to patient choice and increasing flexibility during long-term IgRT

Subcutaneous Gammanorm® by pump or rapid push infusion: Impact of the device on quality of life in adult patients with primary immunodeficiencies

Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), secondary endpoints were QoL (SF36v2), satisfaction (TSQM-11), disease and treatment burden (PRISM), incidence of infections and adverse events (AE), treatment costs, and IgG levels. 28/30 patients completed the study. Most of the endpoints were comparable. Drug administrations with rapid push were more frequent, but reduced total time expenditure and some costs. Of the TSQM-11/LQI/SF36 components only "treatment interference with daily activities" was superior with pump and two QoL domains with rapid push. Both delivery devices showed favorable safety. Rapid push was preferred by 34.5% of patients. It proved to be an efficacious and cost-effective alternative to pumps adding to patient choice and increasing flexibility during long-term IgRT