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.

Real-world severe asthma biologic administration and adherence differs by biologic: CHRONICLE study results.

BACKGROUND: Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations. OBJECTIVE: To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA. METHODS: CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment. RESULTS: A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients. CONCLUSION: Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03373045.

Self-contained underwater breathing apparatus diving and asthma: Where are we in 2023?

Asthma is a risk factor for an adverse event while diving utilizing self-contained breathing apparatus (SCUBA). There are various consensus-based recommendations suggesting criteria to evaluate a person with asthma and allow safe SCUBA diving. A systematic review of the medical literature using Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) was published in 2016 and concluded there is limited evidence, but subjects with asthma are likely at increased risk of adverse if events if participating in SCUBA. This previous review also included there are insufficient data to inform the decision for a specific patient with asthma to dive. The search strategy used in 2016 was repeated in 2022 and is reported in this article. The conclusions are the same. Suggestions for the clinician are provided to assist in the shared decision-making discussion related to an asthma patient's request to participate in recreational SCUBA diving.

Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective-a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee.

Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

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.

Impact of the COVID-19 Pandemic on Incidence of Asthma Exacerbations and Hospitalizations in US Subspecialist-Treated Patients with Severe Asthma: Results from the CHRONICLE Study.

Purpose: Patients with severe asthma (SA) are at an increased risk of asthma-related hospitalizations and exacerbations. Despite concerns that COVID-19 circulation would increase exacerbations of SA, anecdotal reports suggest that social distancing and exposure avoidance may have led to reduced exacerbations. Patients and methods: CHRONICLE is an ongoing noninterventional observational study of 3100 subspecialist-treated patients with SA. Eligible adults (≥ 18 years of age) have (1) current use of monoclonal antibody (ie, biologic) therapy for SA, (2) use of maintenance systemic corticosteroids (mSCS) or other systemic immunosuppressants for ≥ 50% of the prior 12 months for SA, or (3) persistently uncontrolled asthma while treated with high-dosage inhaled corticosteroids with additional controllers. For enrolled patients, electronic medical records were reviewed to record all exacerbations and asthma-related hospitalizations. Descriptive analyses were conducted of the monthly incidence of exacerbations, exacerbation-related visits to the emergency department (ED), and asthma hospitalizations from July 2018 through July 2021. Results: Exacerbations, exacerbation-related ED visits, and hospitalizations decreased since April 2020. Exacerbations in 2020 were 20% to 52% lower in April through August relative to the same months in 2019. Exacerbations remained lower than the prior year through May 2021. Similar results were observed by United States (US) census region, with an earlier decrease in exacerbation rates in the western US versus other regions. Across all months, exacerbation rates were lower among biologic recipients. Conclusion: In a clinical cohort of subspecialist-treated patients with SA, there was a meaningful reduction in exacerbations, exacerbation-related ED visits, and asthma hospitalizations following COVID-19-related stay-at-home orders and social distancing recommendations. Reasons for these reductions are likely multifactorial, including reduced viral infections due to less social contact and altered patient behavior.

Clinical implications of asthma endotypes and phenotypes.

Background: Asthma is a complex disorder with variable clinical expression. Recognizable clinical and laboratory features define phenotypes, and specific biologic pathways define endotypes. Identifying the specific pathway responsible for persistent asthma would enable the clinician to select the optimal inhibitors, which currently are biologic therapies. Objective: To provide an up-to-date review of the current clinical status of endotype and phenotype characterizations of asthma and discuss these categories in relation to the available, or likely available, biologic therapies for asthma. Methods: The medical literature was reviewed based on the search terms: asthma biologics, severe asthma, uncontrolled asthma, corticosteroid-dependent asthma, phenotype, endotype, and type 2. We also used our knowledge of the literature and current research. Results: All of the current biologics, including the recently approved tezepelumab, were most effective with increased type 2 biomarkers, which identify exacerbation-prone asthma. Current biomarkers do not permit consistent identification of specific endotypes to facilitate informed selection of the optimal therapy for an individual patient. Thus, empiricism and the art of care continue to play major roles in treatment selection. Conclusion: Current biologic therapies for asthma and those likely to be U.S. Food and Drug Administration approved within the near future work best in subjects with strong type 2 signatures. Available biomarkers and observable characteristics do not enable clinicians to recognize specific endotypes, but rather subphenotypes or overlapping endotypes. The goal of identifying the optimal patient for a specific therapy remains elusive, but worthy of pursuit. In the interim, the availability of an increasing number of treatment options allows the clinician to help most of his or her patients.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Biologic use and outcomes among adults with severe asthma treated by US subspecialists.

BACKGROUND: Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States. OBJECTIVE: To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described. RESULTS: Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (> 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both P < .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E. CONCLUSION: Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03373045.

Anaphylaxis: Definition, Epidemiology, Diagnostic Challenges, Grading System.

There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization's Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.

Atopy: A Collection of Comorbid Conditions.

The concept of atopy was initially developed in the first quarter of the 20th century on the basis of clinical observations without any knowledge of pathogenic mechanisms. Atopy involves a collection of comorbidities that share pathogenic features, and atopic comorbidities affect outcomes of concomitant conditions rather than existing synchronously. The clinical importance of understanding the relationship of these conditions is necessary because the treatment of one condition influences the others, and the development of one leads to or precedes the development of another. Environmental influences and multigenetic predispositions result in complex relationships among the atopic conditions sharing a type 2 pathogenesis. The specialty of Allergy and Immunology is devoted to managing the comorbidities of atopy, and better understanding of their connections can improve patient care.

Erratum to "IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper" [World Allergy Organ J 13/2 (2020) 100080].

[This corrects the article DOI: 10.1016/j.waojou.2019.100080.].

Mechanisms of non-type 2 asthma.

Non-type 2 inflammation (Non-T2)-mediated asthma is difficult to define due to lack of signature biomarkers. It exists in the absence of T2-high or eosinophilic inflammation and includes neutrophilic and paucigranulocytic subtypes. Several cell types and cytokines, including Th1, Th17, IL-6, and IL-17, contribute to mechanisms of non-T2 asthma. Neutrophil extracellular traps (NETs) and inflammasome activation likely play a role in severe neutrophilic asthma. Several mechanisms lead to uncoupling of airway hyperresponsiveness and remodeling from airway inflammation in paucigranulocytic asthma. Recent research on transcriptomics and proteomics in non-T2 asthma is discussed in this review. Investigations of specific drug therapies for non-T2 asthma have been disappointing, and remain an important area for future clinical studies.

The CHRONICLE Study of US Adults with Subspecialist-Treated Severe Asthma: Objectives, Design, and Initial Results.

BACKGROUND: Approximately 5-10% of patients with asthma have severe disease. High-quality real-world studies are needed to identify areas for improved management. OBJECTIVE: Aligned with the International Severe Asthma Registry, the CHRONICLE study (ClinicalTrials.gov: NCT03373045) was developed to address this need in the US. STUDY DESIGN: Learnings from prior studies were applied to develop a real-world, prospective, noninterventional study of US patients with confirmed severe asthma who are treated by subspecialist physicians and require biologic or maintenance systemic immunosuppressant therapy or who are uncontrolled by high-dosage inhaled corticosteroids and additional controllers. Target enrollment is 4000 patients, with patient observation for ≥3 years. A geographically diverse sample of allergist/immunologist and pulmonologist sites approach all eligible patients under their care and report patient characteristics, treatment, and health outcomes every 6 months. Patients complete online surveys every 1-6 months. INITIAL RESULTS: From February 2018 to February 2019, 102 sites screened 1428 eligible patients; 936 patients enrolled. Study sites (40% allergist/immunologist, 42% pulmonologist, 18% both) were similar to other US asthma subspecialist samples. Enrolled patients were 67% female with median ages at enrollment and diagnosis of 55 (range: 18-89) and 26 (0-80) years, respectively. Median body mass index was 31 kg/m2; 3% and 29% were current or former smokers, respectively, and >60% reported ≥1 exacerbation in the prior year and suboptimal symptom control. CONCLUSION: CHRONICLE will provide high-quality provider- and patient-reported data from a large, real-world cohort of US adults with subspecialist-treated severe asthma.

Biologic and maintenance systemic corticosteroid therapy among US subspecialist-treated patients with severe asthma.

BACKGROUND: Severe asthma (SA) often requires subspecialist management and treatment with biologic therapies or maintenance systemic corticosteroids (mSCS). OBJECTIVE: To describe contemporary, real-world biologic and mSCS use among US subspecialist-treated patients with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of US adults with SA treated by allergists/immunologists or pulmonologists. Eligible patients are receiving biologics or mSCS or are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Biologic and mSCS use patterns and patient characteristics were summarized for patients enrolled between February 2018 and February 2019. RESULTS: Among protocol-eligible patients, 58% and 12% were receiving biologics and mSCS, respectively, with 7% receiving both. Among 796 enrolled, most were women (67%), non-Hispanic white (71%), of suburban residence (50%), and had elevated body mass index (median: 31). Respiratory and nonrespiratory comorbidities were highly prevalent. With biologics (n = 557), 51% were anti-immunoglobulin E and 48% were anti-interleukin (IL)-5/IL-5Rα; from May 2018, 76% of initiations were anti-IL-5/IL-5Rα. In patients receiving mSCS, median prednisone-equivalent daily dose was 10 mg. Multivariate logistic regression found that patients of hospital clinics, sites with fewer nonphysician staff, and with a recorded concurrent chronic obstructive pulmonary disease diagnosis were less likely to receive biologics and more likely to receive mSCS. CONCLUSION: In this real-world sample of US subspecialist-treated patients with SA not controlled by high-dosage inhaled corticosteroids with additional controllers, mSCS use was infrequent and biologic use was common, with similar prevalence of anti-immunoglobulin E and anti-IL-5/IL-5Rα biologics. Treatment differences associated with patient and site characteristics should be investigated to ensure equitable access to biologics and minimize mSCS use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03373045.

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.