Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Trends in the proportion of women speakers at North American Allergy and Immunology conferences, 2008 to 2020.

BACKGROUND: Women in medicine continue to be underrepresented at medical conferences. Previous studies have evaluated the proportion of invited female speakers across multiple specialties and evaluated factors that may have led to this disparity. The field of Allergy and Immunology has often been excluded and analyses have not illustrated how the trends have changed over the past decade. OBJECTIVE: To evaluate the distribution of invited speakers by gender over time at the 3 largest North American Allergy and Immunology conferences. METHODS: This retrospective longitudinal analysis used conference programs from 2008 to 2020 from the American Academy of Allergy, Asthma, and Immunology (AAAAI), the American College of Allergy, Asthma, and Immunology (ACAAI), and the Canadian Society of Allergy and Clinical Immunology (CSACI). The gender (binary definition, man or woman, based on names, photos, pronouns, from conference programs and institutional profiles) of invited speakers was analyzed as the primary outcome, and planning committee members, and multispeaker sessions as secondary outcomes. These data were compared with publicly available data on the composition of the specialty by gender in the United States and Canada. RESULTS: Women speakers at AAAAI, ACAAI, and CSACI conferences have historically been lower than male speakers and underrepresented compared with specialty composition. However, there has been a significant increase in the proportion of women speakers over time for all 3 conferences individually (AAAAI: 23.7% in 2008, 41.1% by 2020; ACAAI: 16.7% in 2008, 37.3% by 2020; CSACI: 19.4% in 2008, 54.8% by 2020; P < .001 for each) and combined (21.3% in 2008, 40.7% by 2020, P < .001). This trend coincides with a significant increase in women on the planning committee (all conferences: 20% in 2008, 50.6% by 2020; P < .001). There is also a decreasing trend over time for men-only multispeaker sessions. CONCLUSION: This study sheds light on the trends of women speaker representation at Allergy and Immunology conferences and provides clarity on future needs to reach equal representation in this field.

The mental health impact of the COVID-19 pandemic on post-secondary students: A longitudinal study.

This prospective longitudinal study measured sex-specific changes in depression, anxiety, and stress scores using, validated Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Perceived Stress Scale (PSS) in a cohort of 1445 post-secondary students (500 males, 945 females) assessed at three time points from December 2020 to January 2022. Participants were ascertained from a population of 15,585 students with in-person activities on campus at baseline and recruited from December 2020 to January 2021. We also assessed how sociodemographic characteristics influenced students' mental health outcomes. Inverse probability weighting was used to account for missing data and attrition. Linear mixed effects models were used to analyze the relationship between the mental health scores in each questionnaire, demographic and academic data, and public health stringency measured by the local stringency index. No change was observed in questionnaire scores over time for males and females, but the stringency index was significantly associated with increased stress. Being in a non-health-related-field or being white affected males and females differently for stress and anxiety, but not depression. Demographics tended to be more influential on females' mental health than males. In conclusion, mental health resource allocation in time of emerging pandemic could benefit from targeted interventions.

Anxiety in adults with asthma during the coronavirus disease 2019 pandemic: a Canadian perspective.

BACKGROUND: Asthma is a chronic airway inflammatory disease that affects millions of Canadians and often contributes to higher levels of anxiety among patients. Since the coronavirus disease 2019 (COVID-19) pandemic was a time of increased anxiety and fear among the Canadian population, it was thought that those with asthma may experience heightened anxiety levels due to uncertain access to care, the potential to misinterpret asthma symptoms for symptoms of COVID-19 (or vice versa), and the concern about being treated differently by those around them when experiencing asthma symptoms. Therefore, this study sought to perform a cross-sectional analysis of the asthma-anxiety relationship in adults with and without asthma in the unique context of the COVID-19 pandemic from a Canadian perspective. METHODS: This study employed the COVID-19 Associated Anxiety in Allergic Rhinitis and Asthma patients Experiencing Symptoms (CAAARES) survey, consisting of COVID-19-specific questions, the Generalized Anxiety Disorder Assessment-7 (GAD-7) and the Asthma Control Questionnaire-6 (ACQ-6). Data collection occurred through the Qualtrics XM platform and data analyses were conducted with the IBM SPSS Statistics 28 software. RESULTS: A total of 741 valid responses were collected (asthma group, n = 244; control group, n = 497). 31.6% and 26.2% of respondents in the asthma and control groups, respectively, met the diagnostic criteria for GAD. There was no significant difference (p = .067) in mean GAD-7 scores between the two groups. A Hierarchal Multiple Regression (HMR) model was developed, and neither asthma status nor ACQ-6 score had a significant predictive effect on the GAD-7 score. There was a statistically significant (p < .001) weak positive correlation (r = .22) between GAD-7 and ACQ-6 scores. In a simple mediation (SMM) model, perceived COVID-19 stress of others was not identified as a significant mediator of the relationship between ACQ-6 and GAD-7 (indirect effect ß = 0.014). CONCLUSION: Our study of a Canadian cohort demonstrates elevated levels of anxiety overall, amongst both asthma and control groups. While AR status was significantly greater in the asthma group, it was not a significant predictive variable of GAD-7 score. Our data suggests that COVID-19-specific factors appear to have a greater contribution to anxiety than asthma status or control.

Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection.

BACKGROUND: Epinephrine is the first-line treatment for severe allergic reactions, and rapid treatment is associated with lower rates of hospitalization and death. Current treatment options (epinephrine auto-injectors and manual intramuscular injection) are considered cumbersome, and most patients/caregivers fail to use them, even during severe reactions. An intranasal epinephrine delivery device, neffy, has been designed to provide an additional option for patients/caregivers. OBJECTIVE: We sought to assess the comparative pharmacokinetics and pharmacodynamics of neffy 2.0 mg, EpiPen 0.3 mg, and manual intramuscular injection 0.3 mg. METHODS: This was a phase 1, randomized, 6-treatment, 6-period, 2-part crossover study in 59 healthy subjects. Pharmacokinetic and pharmacodynamic parameters following single and repeat doses of epinephrine were assessed before dosing and at various postdose intervals. RESULTS: The pharmacokinetic profile of neffy was bracketed by approved injection products, with a mean peak plasma level of 481 pg/mL, which fell between EpiPen (753 pg/mL) and epinephrine manual intramuscular injection (339 pg/mL). When dosed both once and twice, neffy resulted in more pronounced increases in pharmacodynamic parameters relative to EpiPen or manual injection. CONCLUSIONS: neffy's pharmacokinetic profile was bracketed by approved injection products, with pharmacodynamic responses that were comparable to or better than approved injection products. neffy is expected to be a safe and effective option, particularly for patients/caregivers who are reluctant to carry and use injection devices.

Evidence-based use of antihistamines for treatment of allergic conditions.

Available since the 1940s, H1 antihistamines are mainstay treatments for allergic conditions such as allergic rhinitis and urticaria. They function as inverse agonists that bind to the H1 receptor to inhibit histamine-induced inflammation. The older, first-generation drugs are no longer recommended for patient use because of their well-documented negative adverse effect profile. Evidence has been accumulating to support a newer generation of H1 antihistamines in oral and intranasal formulations, including in combination with intranasal corticosteroids. The literature is replete with large meta-analyses and systematic reviews establishing the safety and efficacy of second-generation H1 antihistamines in adult and pediatric allergic rhinitis populations, including combination nasal spray agents (eg, MP29-02 or MP-AzeFlu). Although intraclass differences do exist, patient preference, access, and costs should be the priority. Robust data on the regular, not as needed use of H1 antihistamines for urticaria have been published, including in the management of children and pregnant or lactating women. In addition, H1 antihistamines can be used in other related allergic conditions, such as the secondary symptoms of anaphylaxis, to provide patients with greater comfort, including in allergic asthma, depending on the individual.

Updated guidance regarding the risk of allergic 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 >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.

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis.

Background and aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe. PROSPERO registration number: CRD42021265689.

Utility of eConsults for COVID-19 vaccine-related concerns in Ontario: a cross-sectional analysis.

BACKGROUND: The Champlain BASE™ and Ontario eConsult services are virtual platforms that serve to facilitate contact between primary care providers and specialists across Ontario, relaying patient-specific questions to relevant specialists via a secure web-based platform. Despite ample evidence regarding the general effectiveness of these platforms, their utility as it pertains to clinical concerns regarding COVID-19 vaccines has not yet been explored. METHODS: We performed a cross-sectional descriptive analysis of COVID-19 vaccine related eConsults on Ontario patients completed by five allergy specialists between February and October of 2021. 4318 COVID-19 vaccine-related eConsults were completed in total during this time; with 1857 completed by the five allergists participating in this analysis. Question types/content were categorized using a taxonomy developed through consensus on a weighted monthly sample of 499 total cases. Data regarding whether external resources were required to answer each eConsult, impact on primary care provider referral decisions, and allergy consultant response times were collected. A 2-question survey was completed by primary care providers following eConsultation and results were collected. RESULTS: 41.08% of eConsults received involved safety concerns regarding COVID-19 vaccine administration in the setting of prior allergic disease and another 36.1% involved a potential reaction the first dose of a COVID-19 vaccine. 72.1% of eConsults were answered by specialist without needing external resources, and only 9.8% of all eConsults received resulted in a recommendation for formal in-person referral to Clinical Immunology & Allergy specialist or another subspecialty. Average time to complete eConsult was 16.4 min, and 79.7% of PCP eConsult queries which would have traditionally resulted in formal consultation were resolved based on advice provided in the eConsult without need for in-person assessment. CONCLUSIONS: Our study demonstrates the utility of the eConsult service as it pertains to COVID-19 vaccine-related concerns. The eConsult platform proved an effective tool in diverting the need for in-person assessment by an Allergist or other medical specialty. This is significant given the large volume of eConsults completed by Allergists, and demonstrates the impact of an effective electronic delivery of care model during a time of strained resources and public health efforts directed at mass vaccination.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting.

The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18-29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.

Minimization of ragweed allergy immunotherapy costs through use of the sublingual immunotherapy tablet in Canadian children with allergic rhinoconjunctivitis.

BACKGROUND: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC. METHODS: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes. RESULTS: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios. CONCLUSIONS: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.

Epinephrine autoinjectors: individualizing device and dosage to optimize anaphylaxis management in the community setting.

Background: Anaphylaxis is the most severe manifestation of a systemic allergic reaction, and, in the community setting, the immediate administration of an epinephrine autoinjector (EAI) can be life-saving. Physicians are tasked with selecting the most appropriate EAI for each individual and counseling patients and/or their caregivers to maximize the likelihood of successful deployment of the EAI. Objective: To offer an evidence-based expert clinical perspective on how physicians might best tailor EAI selection to their patients with anaphylaxis. Methods: A group of eight adult and pediatric allergists with expertise in anaphylaxis management reviewed and assessed the published data and guidelines on anaphylaxis management and EAI device selection. Results: Personalized EAI selection is influenced by intrinsic individual factors, extrinsic factors such as the properties of the individual EAI (e.g., dose, needle length, overall design) as well as cost and coverage. The number and the variety of EAIs available have expanded in most jurisdictions in recent years, which provide a greater diversity of options to meet the characteristics and needs of patients with anaphylaxis. Conclusion: There currently are no EAIs with customizable dose and needle length. Although precise personalization of each patient's EAI remains an optimistic future aspiration, careful consideration of all variables when prescribing EAIs can support optimal management of anaphylaxis.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.