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Wendy C Moore,1 Dennis K Ledford,2 Donna D Carstens,3 Christopher S Ambrose4 1Wake Forest School of Medicine Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC, USA; 2Morsani College of Medicine, University of South Florida, and James A. Haley Veterans’ Hospital, Tampa, FL, USA; 3BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 4BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USACorrespondence: Wendy C Moore, Wake Forest School of Medicine Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Medical Center Boulevard, Winston-Salem, NC, 27157, USA, Tel +1 336-716-7765, Fax +1 336-716-7277, Email wmoore@wakehealth.eduPurpose: 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.Keywords: management/control, healthcare resource use

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Tang, Mimi/0000-0002-3839-5293; Romano, Antonino/0000-0001-9742-9898; Zuberbier, Torsten/0000-0002-1466-8875; Thong, Bernard/0000-0002-6338-8482; EBO, Didier/0000-0003-0672-7529; Scala, Enrico/0000-0002-9391-9168; Monge Ortega, Olga Patricia/0000-0002-6195-417X WOS:000523267300003 PubMed: 32128023 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. WAO Board of Directors The authors wish to thank the allergy societies from the membership of the World Allergy Organization who provided critical review of the draft and the WAO Board of Directors for supporting this work.

Allan T Luskin,1 Evgeniya N Antonova,2 Michael S Broder,3 Eunice Y Chang,3 Theodore A Omachi,2 Dennis K Ledford4 1HealthyAirways, Madison, WI, 2Genentech, Inc., South San Francisco, 3Partnership for Health Analytic Research, LLC, Beverly Hills, CA, 4Division of Allergy and Immunology, Department of Medicine, James A. Haley Veterans’ Hospital, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Background: The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma.Methods: This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status.Results: After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P

The world allergy organization guidelines for the assessment and management of anaphylaxis are being published concurrently in the journal of allergy and clinical immunology to facilitate retrieval by all health care professionals worldwide through pubmed and other search engines and in the world allergy organization journal to facilitate rapid access by all members of the wao. The recommendations for assessment and basic initial management of anaphylaxis, as summarized in fig 1, fig 2, fig 3, fig 4, fig 5 and in table 1, table 2, table 3, table 4, table 5, table 6, table 7, table 8, table 9 in the guidelines, are also being disseminated through posters, pocket cards, and applications (apps) for mobile devices.the main barriers to implementation of the recommendations in the guidelines include the erroneous perception that anaphylaxis is a rare disease and the lack of universal availability of essential medications, supplies, and equipment for its assessment and management worldwide. Additional barriers include lack of awareness that hypotension and shock are often absent in patients with anaphylaxis, that serum tryptase or plasma histamine levels are not necessarily increased, that death can occur within a few minutes, and that prompt basic initial treatment can be life-saving.the wao member societies were extensively involved in the development of these unique anaphylaxis guidelines, and will be involved with their dissemination and implementation. Their continued anaphylaxis education efforts will help to surmount the above-listed barriers.in the online full-length version of the world allergy organization guidelines for the assessment and management of anaphylaxis, available at www.jacionline.org, a complete list of references is provided to support the recommendations that are made.

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010.The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously).The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed. Keywords: anaphylaxis, risk factors, clinical diagnosis, epinephrine (adrenaline), antihistamines, glucocorticoids

Allergen immunotherapy (AIT) is widely used in clinical practice for patients with moderate to severe allergic rhinitis due to inhalant allergens and may be delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the quality of evidence for individual AIT products is very heterogeneous, and extensions of overall conclusions ("class effects") on the efficacy and disease-modifying effects to all AIT products are unjustified. In contrast, each product needs to be evaluated individually, based on available study results, to justify efficacy and specific claims on sustained and disease modifying effects per allergen and targeted patient group (children vs. adults, allergic rhinitis vs. asthma). WAO intends to support the current development to evidence-based AIT, which ultimately will lead to a more efficacious treatment of allergic patients and the appropriate recognition of AIT.

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. A World Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.

BackgroundRespiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.MethodsSince the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined.ResultsThe group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal.ConclusionTogether, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

Erratum Following the publication of our article [1], we noticed that Dr Flavia C. L. Hoyte had inadvertently been omitted from the author list. FCLH declares she has no conflicts of interest. The author list has now been corrected and the amended authors contributions section included below. AY initiated and led the development of the paper as primary author, contributing to all of the sections and unifying the document. SCH and STH were co-project leaders. SHC wrote the Introduction. JC and CEB wrote on the impact of asthma. LPB and GWC wrote on management of asthma. RK, FCLH, PB, LF, AK, KR, and LR wrote on the aging lung. DKL, SHC, SP, and GJR wrote on diagnosis. JBS wrote on life expectancy. All authors reviewed and approved the final document.

Methods Data from the National Asthma Survey were analyzed to compare asthma control in children (5 to 11 yrs) using ICS/LABA vs. ICS alone. Both short term (symptoms within last 2 weeks, day and night symptoms in last 30 days and use of systemic glucocorticoids in last 3 months) and long term (asthma attack, emergency department visits, hospitalizations and activity limitations in the prior year) outcomes were compared. Demographics, availability of health insurance, indoor allergen exposure and asthma education were compared between the two groups. Asthma control in an adult population (18 to 44 years) was also assessed for the same parameters.

Background We report the case of a patient with 3 forms of physical urticaria and his response to treatment. Methods An atopic asthmatic 11 year old male was evaluated for a history of recurrent pruritus with a variable, erythematous rash unresponsive to therapy. Since the age of 5 years, he has experienced small red, raised, pinpoint, pruritic “bumps” over his entire body except the palms of his hands and soles of his feet. The duration of the lesions was generally 5 minutes to about 1 hour. They occurred with exercise, stress, cold air, and cold water. At the time of the evaluation, the patient was treated with oral levocetirizine 5 mg daily and hydroxyzine 50 mg at bedtime without resolution of symptoms. Results In clinic, the patient had a positive ice cube test, a positive dermatographia test and a negative warm test tube test. Methacholine and autologous sweat testing were declined. Otherwise he had a normal physical examination with a negative Darier sign. Laboratory studies did not reveal a disease process responsible for the urticaria. Based upon his historical symptoms and clinical findings, he was diagnosed with 3 distinct types of physical urticaria; cholinergic urticaria, cold urticaria and dermatographia. The dose of anti-histamine therapy was doubled and the patient returned to clinic in 4 weeks to report that his symptoms were slightly improved but had not resolved. Conclusions Physical urticarias are usually controlled by antihistamine therapy but refractory cases are not uncommon. This patient also has poorly controlled asthma for which he is scheduled to start omalizumab therapy upon turning 12 in 1 month. We will continue to follow this case to observe if omalizumab has an effect upon his urticarial symptoms.