Hereditary angioedema (HAE) is a rare, genetic condition treated with plasma-derived human C1 esterase inhibitor (C1-INH). Little is known about patient geographic distribution and patterns of use. The project aim was to understand how and where C1-INH product is being used to treat HAE in Canada. An online survey using REDCap was distributed by email to hospitals that had received C1-INH from the blood supplier between December 2019 and November 2020. Hospital demographics, contact information and C1-INH use in-hospital and by patients at home was requested. Descriptive analyses were performed. Calculation of IUs of C1-INH from vial numbers used by hospitals was assumed to follow the national distribution of vial sizes (1500 and 500 IUs). Research Ethics Board approval was not required. Respondents: 83/181 hospitals (47.5%) that received C1-INH responded: 39 from Ontario; 35 from Alberta and British Columbia combined and 9 from other provinces. The 83 hospitals represented 52.3% of the C1-INH product distributed nationally. Patients: 221 patients received 1844 vials (2.6 million IUs) of C1-INH in a hospital setting: 138 in the emergency department (62.4 %), 53 as inpatients (24.0%), and 30 in out-patient clinics (13.6%). The total number of hospital patient encounters was 615 with the out-patient clinic having the highest proportion (52.5%). For home care use, 68 hospitals (81.9%) issued product to 239 patients; 67.8% were female. The most common age category was 30–44 years but in Ontario the age demographic was slightly older (45–59 years). Distribution and use: The total number of C1-INH units issued to all hospitals in Canada was 62,260,000; of which 32,568,000 units were issued to the 83 responding hospitals. There were 2,616,000 IUs of C1-INH transfused in hospitals, 424,500 IUs transferred to other hospitals and 101,000 IU discarded. For home care, 31,395,000 IUs were transfused; hence, home care use accounted for 92% of product issued. This project gives a Canadian snapshot of the distribution and use of C1-INH both in hospitals, and at home for patients with HAE, with most patients residing in three provinces and the majority of product being used for home care. Further information is required to understand the proportion of home product used on-demand versus prophylactically.

Abstract Background In Canada, severe asthma affects an estimated 5–10% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as the high dose inhaled, and systemic steroids used to treat it. Significant heterogeneity exists in service structure and patient access to severe asthma care, including access to biologic treatments. There appears to be over-reliance on short-acting beta agonists and frequent oral corticosteroid use, two indicators of uncontrolled asthma which can indicate undiagnosed or suboptimally treated severe asthma. The objective of this modified Delphi consensus project was to define standards of care for severe asthma in Canada, in areas where the evidence is lacking through patient and healthcare professional consensus, to complement forthcoming guidelines. Methods The steering group of asthma experts identified 43 statements formed from eight key themes. An online 4-point Likert scale questionnaire was sent to healthcare professionals working in asthma across Canada to assess agreement (consensus) with these statements. Consensus was defined as high if ≥ 75% and very high if ≥ 90% of respondents agreed with a statement. Results A total of 150 responses were received from HCPs including certified respiratory educators, respirologists, allergists, general practitioners/family physicians, nurses, pharmacists, and respiratory therapists. Consensus amongst respondents was very high in 37 (86%) statements, high in 4 (9%) statements and was not achieved in 2 (5%) statements. Based on the consensus scores, ten key recommendations were proposed. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures. Conclusions Implementation of these recommendations across the severe asthma care pathway in Canada has the potential to improve outcomes for patients through earlier detection of undiagnosed severe asthma, reduction in time to severe asthma diagnosis, and initiation of advanced phenotype specific therapies.

Budesonide orodispersible tablets (BOT) have been approved in Europe and Canada for the treatment of eosinophilic esophagitis (EoE), a rare and chronic disease. The objective of this study was to assess the economic impact of BOT on both the induction and maintenance of clinico-pathological remission of EoE by performing a cost–utility analysis (CUA). For both the induction and maintenance settings, BOT was compared to no treatment in a target population of adult patients with EoE non-responsive to proton pump inhibitor (PPI) treatment. Markov models were developed for the induction and maintenance settings over 52-week and life-time horizons, respectively. Analyses were performed from both a Canadian Ministry of Health (MoH) and societal perspective. The resulting incremental cost–utility ratios (ICURs) were compared to a willingness-to-pay (WTP) threshold of $50,000 Canadian dollars/quality-adjusted life-year (QALY). Sensitivity and scenario analyses were conducted to assess the robustness of the base-case results. In the base-case probabilistic analysis, BOT compared to no treatment resulted in an ICUR of $1073/QALY and $30,555/QALY from a MoH perspective in the induction and maintenance settings, respectively. BOT was a cost-effective option for both induction and maintenance in > 99% of Monte Carlo simulations. In the scenario analyses, the deterministic ICUR of BOT compared to no treatment varied from $682/QALY to $8510/QALY in the induction setting and $21,005/QALY to $55,157/QALY in the maintenance setting. BOT was cost-effective compared to no treatment for both the induction and maintenance of clinico-pathological remission of EoE in patients non-responsive to PPIs.

The reference sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) were renewed in 2019. The DG Santé good practice Mobile Airways Sentinel networK was reviewed to meet the objectives of the EIP on AHA. It included 1) Management of care process, 2) Blueprint of digital transformation, 3) EIP on AHA, innovation to market, 4) Community for monitoring and assessment framework, 5) Political, organizational, technological and financial readiness, 6) Contributing to European co-operation and transferability, 7) Delivering evidence of impact against the triple win approach, 8) Contribution to the European Digital Transformation of Health and Care and 9) scale of demonstration and deployment of innovation.

The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

Introduction: Hereditary angioedema (HAE) patients (both diagnosed and undiagnosed) commonly present to the emergency department (ED). Presenting symptoms (swelling and pain) may be erroneously attributed to common allergic and gastrointestinal conditions resulting in major delays in diagnosis and appropriate treatment. No published tools currently exist for HAE screening and management in undiagnosed disease. The overall goal of the study was to develop a HAE-RT tool for ED settings. Methods: A two-phase mixed methods approach was used to develop the HAE-RT Tool including: Phase 1: A Delphi Study [HAE specialists (N=9) and National Patient Advocacy Group Members (N=3)] was conducted to reach consensus (80% agreement) on predictor variables to include. Phase 2: A retrospective chart review was conducted to assess the predictive findings of the predictor variables. A convenient sample of patients presenting with angioedema (with and without HAE) between January 2012 January 2017 were included in the study. Results: Of the 12 experts invited, 9 (75%) participated in the Delphi study. Of 8 HAE-specific predictive variables, 4 reached consensuses including: (1) recurrent angioedema; (2) absence of urticaria; (3) past recurrent abdominal pain/swelling; (4) response to allergic therapy. The retrospective study included 85 patients (N=46 with HAE; N=39 non-HAE; overall 72% female). HAE patients were significantly more likely to have a family history of HAE (72% vs 0%; P<0.0001); previous recurrent angioedema (96%; P<0.009); present with no hives (91%; P<0.036); previous recurrent abdominal pain (80%; P<0.0001); and only 2% responded positively to allergy treatments (P<0.0001). Conclusion: Our study emphasizes the importance of key stakeholder involvement and feedback to facilitate the prioritization of important information that must be included in the design of an HAE-RT tool. The next step is to observe the effect of the HAE-RT tool on patient triage in the ED.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization (WHO) workshop in 1999. The initial goals were (i) to propose a new allergic rhinitis classification, (ii) to promote the concept of multi-morbidity in asthma and rhinitis and (iii) to develop guidelines with all stakeholders for global use in all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK (MACVIA (Contre les MAladies Chroniques pour un VLeillissement Actif)-ARIA Sentinel NetworK) uses mobile technology to develop care pathways in order to enable the management of rhinitis and asthma by a multi-disciplinary group or by patients themselves. An App (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

BACKGROUND:The generation of IgE-mediated food allergy in humans is silent and only diagnosed upon manifestation of clinical symptoms. While experimental models have been used to investigate some mechanisms of allergic sensitization, the generation of humoral immunity and memory remains to be elucidated. Here, we defined the evolution of allergen-specific B-cell responses during epicutaneous sensitization to foods.METHODS:Wild-type and genetic knockout animals, and drug or antibody strategies for cell depletion and immunoglobulin signaling blockade were used to investigate epicutaneous sensitization and disease progression; we analyzed allergen-specific germinal centers and IgG1+ memory B cells by flow cytometry, evaluated humoral responses, and determined clinical reactivity (anaphylaxis).RESULTS:Epicutaneous sensitization caused microscopic skin damage, inflammation, and recruitment of activated dendritic cells to the draining lymph nodes. This process generated allergen-specific IgG1+ germinal center B cells, serum IgG1, and anaphylaxis that was mediated by the alternative pathway. Whether we used peanut and/or ovalbumin from the egg white for sensitization, the allergen-specific IgG1+ memory compartment predominantly exhibited an immature, pro-germinal center phenotype (PDL-2- CD80- CD35+ CD73+ ). Subsequent subclinical exposures to the allergen induced IgE+ germinal center B cells, serum IgE, and likely activated the classical pathway of anaphylaxis.CONCLUSIONS:Our data demonstrate that IgG1+ B-cell immunity against food allergens in epicutaneous sensitization precedes the generation of IgE responses. Therefore, the assessment of allergen-specific cellular and humoral IgG1+ immunity may help to identify individuals at risk of developing IgE-mediated food allergy and hence provide a window for therapeutic interventions.

Childhood food allergy is a significant public health issue with prevalence rates as high as 10% among children in some countries (1, 2). While the quality and quantity of global data on childhood food allergy have increased in recent years, knowledge on consumer perceptions of issues affecting management is lacking (3, 4). Allergic reactions to food can vary from mild to life-threatening. As a result, the standard recommendation is to strictly avoid the food allergen, which can be complicated when purchasing packaged food. The food industry in most countries is required to label the presence of the most common food allergens when they are ingredients in packaged foods; however, they may voluntarily add precautionary allergen labeling (PAL). These statements, such as ‘may contain. . .’ or ‘processed in a facility that manufactures. . .’, are unregulated, and it is unknown how many products with PAL actually contain trace levels. Consumers must make their own decisions on how to interpret these PAL statements, which can lead to food restrictions that affect the daily lives and well-being of consumers and caregivers (5, 6). A greater understanding of food allergen thresholds (the lowest amount of a food allergen that can cause an allergic reaction) is important to a variety of food allergy stakeholders (7). In 2011, an expert panel was assembled to establish reference doses for 11 allergenic foods as part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program. The doses were obtained from clinical challenges of individuals to establish an eliciting dose for each food at which only a predicted 1–3% of the population would react (8). This study represents the first of its kind to examine differences in perceptions about food allergen thresholds and PAL from the perspective of consumers in 16 countries across the world.

Dining out poses a risk for food allergic individuals. This is accentuated if an epinephrine auto-injector (EAI) is not carried. Our aim was to assess the public perception regarding access to stock epinephrine while dining out. This was part of the first Canadian pilot study on the implementation of a stock epinephrine program.

Chronic spontaneous/idiopathic urticaria (CSU/CIU) is defined as the spontaneous appearance of itchy hives, angioedema, or both lasting ≥6 weeks. CSU/CIU has a significant yet underestimated socioeconomic impact. The ASSURE-CSU study aims to identify and quantify the humanistic and economic burden of CSU/CIU. Here we present Canadian specific data on utility values. The study included a retrospective medical record abstraction, a cross-sectional PRO survey, and 7day diary of patients with CSU/CIU still symptomatic despite treatment, aged ≥18 years, with disease persisting for ≥12 months. Patients completed the weekly Urticaria Activity Score (UAS7) and the EQ-5D-3L, a 2-part instrument comprised of the EQ-5D and the Visual Analog Scale (VAS). ED-5D-3L and VAS utility values were derived using a Canadian-specific scoring algorithm and a standard UK algorithm, respectively. Descriptive statistics were provided for these variables and stratified by disease severity. The cohort included 99 patients with demographics in line with published characteristics of CSU/CIU patients and distributed across severity levels. The instrument was completed by 86 patients. Overall, the mean (SD) EQ-5D utility score was 0.7 (0.30); while the mean (SD) VAS utility score was 71.4 (19.24). The dimensions of the EQ-5D-3L most affected where pain/discomfort and anxiety/depression with 61.4% and 40.9% of patients reporting moderate to extreme problems, respectively. Utility values decreased with increased disease severity for overall and dimension specific scores for both tools. Compared to the average utility score of an average Canadian population (0.875), the results of this study at 0.7 demonstrate that CSU/CIU has a significant impact on patients’ health status and quality of life; with patients suffering from moderate to severe urticaria showing a greater impact on patients’ health state.

BACKGROUND:Food allergy, in particular peanut allergy, is a growing concern in Western countries. The prevalence of allergy to peanut, which currently stands at 1.4%, nearly tripled between 1997 and 2008. Allergic sensitization is a particularly difficult process to study as it is clinically silent. We sought to identify key pathways and mediators critically involved in the induction of allergic sensitization to peanut.METHODS:Comprehensive metabolomics analysis with liquid chromatography-mass spectrometry was used to detect metabolite changes in mice (C57BL/6) undergoing sensitization. Loss-of-function and gain-of-function studies were performed in mice subjected to two models of peanut sensitization and anaphylaxis that involved either oral or epicutaneous sensitization. Flow cytometric analyses on dendritic cells (DCs) in vitro and in vivo were used to investigate the mechanisms of immune activation.RESULTS:Elevated levels of uric acid (UA) were detected in mice undergoing sensitization as well as in peanut-allergic children who were not challenged with peanut. In mice, the depletion of UA during sensitization prevented the development of peanut-specific immunoglobulins IgE and IgG1 as well as anaphylaxis while exogenous delivery of UA crystals (monosodium urate, MSU) restored the allergic phenotype. Monosodium urate enhanced CD86 and OX40L expression on DCs, independent of Toll-like receptors 2 and 4, the NLRP3 inflammasome, and IL-1β, via a PI3K signaling pathway.CONCLUSION:Overproduction of the UA alarmin in the local microenvironment plays a critical role in the induction of peanut-allergic sensitization, likely due to its ability to activate DCs. These finding suggest that cellular damage or tissue injury may be an essential requisite for the development of allergic sensitization to foods.